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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. ;20 kg and 2.2 gm/m2 in individuals >20 kg) can aid in the detoxification of ammonia during neonatal and acute decompensations .Extracorporeal detoxification is required for persistent acidosis and hyperammonemia (plasma ammonia level >250-300 μmol/L) not responding to fluid and drug treatment. Methods include (depending on age and clinical situation) continuous veno-venous hemofiltration, extracorporeal membrane oxygenation, or hemodialysis .Carnitine supplementation (100 mg/kg/day IV divided in 3 doses) may enhance the detoxification of propionic acid by conjugating into propionylcarnitine, which is excreted by the kidneys. Alternatively, it may relieve intracellular coenzyme A accretion and provide a benefit through this mechanism. Consult hospital pharmacy for the recommended maximum daily dose in older patients.Manage pancreatitis using standard practices.Home management of metabolic status. The detection and management of metabolic decompensations at home are a critical part of the chronic management of PA. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. 100 mg/kg/day IV divided in 3 doses) may enhance the detoxification of propionic acid by conjugating into propionylcarnitine, which is excreted by the kidneys. Alternatively, it may relieve intracellular coenzyme A accretion and provide a benefit through this mechanism. Consult hospital pharmacy for the recommended maximum daily dose in older patients.Manage pancreatitis using standard practices.Home management of metabolic status. The detection and management of metabolic decompensations at home are a critical part of the chronic management of PA. Patients and care providers should notify their medical team about new symptoms and discuss the appropriateness of home management. Strategies to achieve home management should be tailored for the conditions of each patient and family and may include the following:At-home detection and monitoring of urine ketonesDiet modification under the direction of the metabolic teamIf fever is present due to an infection, treatment may include paracetamol and ibuprofen .Use of anti-emetics such as ondansetron (see precautionary considerations | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. the chronic management of PA. Patients and care providers should notify their medical team about new symptoms and discuss the appropriateness of home management. Strategies to achieve home management should be tailored for the conditions of each patient and family and may include the following:At-home detection and monitoring of urine ketonesDiet modification under the direction of the metabolic teamIf fever is present due to an infection, treatment may include paracetamol and ibuprofen .Use of anti-emetics such as ondansetron (see precautionary considerations in Agents/Circumstances to Avoid)OtherAny injury, illness, hospitalization, or surgical procedure should involve consultation with the metabolic team.The diagnosis and management of pancreatitis is the same as for pancreatitis of other causes.Neutropenia and other cytopenias usually improve with metabolic control of PA.Management of arrhythmias is similar to that from other causes.Cardiomyopathy may improve after liver transplantation in some patients .Seizures are a frequent complication of PA, necessitating an antiepileptic drug. The use | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. (see precautionary considerations in Agents/Circumstances to Avoid)OtherAny injury, illness, hospitalization, or surgical procedure should involve consultation with the metabolic team.The diagnosis and management of pancreatitis is the same as for pancreatitis of other causes.Neutropenia and other cytopenias usually improve with metabolic control of PA.Management of arrhythmias is similar to that from other causes.Cardiomyopathy may improve after liver transplantation in some patients .Seizures are a frequent complication of PA, necessitating an antiepileptic drug. The use of valproic acid in organic acidemias is often avoided; however, several authors described its use in patients with PA .Dermatologic manifestations (e.g., persistent dermatitis or eczema) warrant a nutritional reassessment to rule out dietary deficiency of essential amino acids, essential fatty acids, vitamins, and minerals.Prevention of Primary ManifestationsDietary management. The mainstay nutritional intervention is modification of diet to control the intake of propiogenic substrates (isoleucine, valine, methionine, and threonine | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. an antiepileptic drug. The use of valproic acid in organic acidemias is often avoided; however, several authors described its use in patients with PA .Dermatologic manifestations (e.g., persistent dermatitis or eczema) warrant a nutritional reassessment to rule out dietary deficiency of essential amino acids, essential fatty acids, vitamins, and minerals.Prevention of Primary ManifestationsDietary management. The mainstay nutritional intervention is modification of diet to control the intake of propiogenic substrates (isoleucine, valine, methionine, and threonine), while ensuring normal protein synthesis and preventing protein catabolism, amino acid deficiencies, and growth restriction.Important note: Dietary management needs to be directed by an experienced physician and metabolic dietician.Recommended protein intake depends on age of the patient (see Baumgartner et al : Table 11).The ratio of natural source protein to medical foods varies depending on the individual’s clinical status, laboratory parameters, and growth trajectory .Laboratory parameters useful in guiding nutritional intervention | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. valine, methionine, and threonine), while ensuring normal protein synthesis and preventing protein catabolism, amino acid deficiencies, and growth restriction.Important note: Dietary management needs to be directed by an experienced physician and metabolic dietician.Recommended protein intake depends on age of the patient (see Baumgartner et al : Table 11).The ratio of natural source protein to medical foods varies depending on the individual’s clinical status, laboratory parameters, and growth trajectory .Laboratory parameters useful in guiding nutritional intervention can include the following:Preprandial plasma essential amino acidsPlasma albuminPrealbuminHemoglobinPlasma ammoniaUrinary ketones, plasma lactic acid, and methylcitric acid to monitor and adjust nutritional managementPlasma vitamin DEssential fatty acid profileAdditional calories can be provided using protein-free formulas.G-tube placement is an effective strategy to facilitate the administration of medications and nutrition during acute decompensations and to improve adherence in chronic management of PA. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. parameters useful in guiding nutritional intervention can include the following:Preprandial plasma essential amino acidsPlasma albuminPrealbuminHemoglobinPlasma ammoniaUrinary ketones, plasma lactic acid, and methylcitric acid to monitor and adjust nutritional managementPlasma vitamin DEssential fatty acid profileAdditional calories can be provided using protein-free formulas.G-tube placement is an effective strategy to facilitate the administration of medications and nutrition during acute decompensations and to improve adherence in chronic management of PA.Since the number of acute decompensations negatively correlates with the intellectual quotient in patients with PA , prevention and proactive management of metabolic crises can be an important point of intervention to maximize favorable clinical outcomes.MedicationsLevocarnitine. The optimal dose of levocarnitine has not been established; doses ranging from 50 to 300 mg/kg per day have been reported .When calculating the daily dose of levocarnitine, one needs to consider the presence of this pharmaceutic compound in | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. in chronic management of PA.Since the number of acute decompensations negatively correlates with the intellectual quotient in patients with PA , prevention and proactive management of metabolic crises can be an important point of intervention to maximize favorable clinical outcomes.MedicationsLevocarnitine. The optimal dose of levocarnitine has not been established; doses ranging from 50 to 300 mg/kg per day have been reported .When calculating the daily dose of levocarnitine, one needs to consider the presence of this pharmaceutic compound in medical foods and the maximum daily dose in older patients.Levocarnitine can be given enterally and intravenously.Antimicrobial therapy. Oral metronidazole has been shown to reduce propionic acid production by intestinal gut flora . One regimen uses a one-week-on, three-weeks-off approach .Biotin supplementation. There is no consensus regarding the use of biotin supplementation nor the optimal dose in the treatment of PA. Given biotin’s favorable profile, a short therapeutic trial may be considered | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. of this pharmaceutic compound in medical foods and the maximum daily dose in older patients.Levocarnitine can be given enterally and intravenously.Antimicrobial therapy. Oral metronidazole has been shown to reduce propionic acid production by intestinal gut flora . One regimen uses a one-week-on, three-weeks-off approach .Biotin supplementation. There is no consensus regarding the use of biotin supplementation nor the optimal dose in the treatment of PA. Given biotin’s favorable profile, a short therapeutic trial may be considered . Whether a biotin-responsive form of PA exists is not known .Management during episodes of metabolic decompensation includes:Avoidance of fasting (e.g., using intravenous dextrose).Increasing calorie intake to prevent catabolism (e.g., intravenous fat emulsion).When enteral feeding cannot be provided for a prolonged period of time, judicious use of total parenteral nutrition may include standard amino acid mixes providing age-appropriate recommended daily allowance of protein . In rare | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. short therapeutic trial may be considered . Whether a biotin-responsive form of PA exists is not known .Management during episodes of metabolic decompensation includes:Avoidance of fasting (e.g., using intravenous dextrose).Increasing calorie intake to prevent catabolism (e.g., intravenous fat emulsion).When enteral feeding cannot be provided for a prolonged period of time, judicious use of total parenteral nutrition may include standard amino acid mixes providing age-appropriate recommended daily allowance of protein . In rare circumstances, specialized amino acid mixes with reduced content of isoleucine, valine, threonine and methionine are necessary.Organ transplantation. Orthotopic liver transplantation (OLT) may be indicated in those individuals who, despite adequate medical treatment, still experience frequent metabolic decompensations, uncontrollable hyperammonemia, and poor growth .Benefits of OLT include decrease in the frequency of metabolic decompensations, improved quality-adjusted life years, increased life expectancy, life-time cost savings , and reversal of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. ance of protein . In rare circumstances, specialized amino acid mixes with reduced content of isoleucine, valine, threonine and methionine are necessary.Organ transplantation. Orthotopic liver transplantation (OLT) may be indicated in those individuals who, despite adequate medical treatment, still experience frequent metabolic decompensations, uncontrollable hyperammonemia, and poor growth .Benefits of OLT include decrease in the frequency of metabolic decompensations, improved quality-adjusted life years, increased life expectancy, life-time cost savings , and reversal of dilated cardiomyopathy .Liver transplantation has been performed from unrelated donors and from heterozygous related donors .Continuous hemofiltration, extracorporeal membrane oxygenation (ECMO) , and left ventricular assist devices have been used while waiting for OLT .OLT in patients with PA is not curative. It does not completely protect against a metabolic stroke, hyperammonemia, or metabolic decompensations.Life-long post-transplant management is recommended . Continued protein restriction and L-carnitine supplementation after OLT is advocated by several | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. cost savings , and reversal of dilated cardiomyopathy .Liver transplantation has been performed from unrelated donors and from heterozygous related donors .Continuous hemofiltration, extracorporeal membrane oxygenation (ECMO) , and left ventricular assist devices have been used while waiting for OLT .OLT in patients with PA is not curative. It does not completely protect against a metabolic stroke, hyperammonemia, or metabolic decompensations.Life-long post-transplant management is recommended . Continued protein restriction and L-carnitine supplementation after OLT is advocated by several authors .Sedation and perioperative management. Anesthetic aspects of perioperative management of patients with PA have been infrequently discussed . Involvement of a metabolic specialist perioperatively to ensure adequate hydration and caloric management can help minimize the risk of decompensations.Emergency situations. Emergency letters, bracelets, and emergency information in smartphones help facilitate appropriate emergency care by healthcare providers unfamiliar with propionic acidemia.Prevention of Secondary ComplicationsRegular monitoring by a biochemical geneticist and a dietitian is necessary to avoid | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. after OLT is advocated by several authors .Sedation and perioperative management. Anesthetic aspects of perioperative management of patients with PA have been infrequently discussed . Involvement of a metabolic specialist perioperatively to ensure adequate hydration and caloric management can help minimize the risk of decompensations.Emergency situations. Emergency letters, bracelets, and emergency information in smartphones help facilitate appropriate emergency care by healthcare providers unfamiliar with propionic acidemia.Prevention of Secondary ComplicationsRegular monitoring by a biochemical geneticist and a dietitian is necessary to avoid insufficient or excessive protein restriction. Many factors should be taken into account to guide protein restriction: age, gender, severity of PA, nutritional status, and presence of other factors such as intercurrent illness, surgery, level of physical activity, and growth spurts. The effects of excessive protein restriction can include impaired growth, essential amino acid deficiencies, and metabolic decompensations.Acrodermatitis enteropathica, hair loss, and cutaneous Candida infections in patients with PA managed with medical | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. itian is necessary to avoid insufficient or excessive protein restriction. Many factors should be taken into account to guide protein restriction: age, gender, severity of PA, nutritional status, and presence of other factors such as intercurrent illness, surgery, level of physical activity, and growth spurts. The effects of excessive protein restriction can include impaired growth, essential amino acid deficiencies, and metabolic decompensations.Acrodermatitis enteropathica, hair loss, and cutaneous Candida infections in patients with PA managed with medical foods can be caused by essential amino acid deficiency and require a re-appraisal of the nutritional management.Psychotic episodes in patients with PA have been infrequently reported . Similar to other inborn errors of metabolism, care should be exercised when using antipsychotic medications as they can mask clinical signs of encephalopathy or cause adverse effects.SurveillanceThe following evaluations are performed at different intervals depending on factors such as age, disease severity, and presence of catabolic stressors; evaluation frequency can range from every three months | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. patients with PA managed with medical foods can be caused by essential amino acid deficiency and require a re-appraisal of the nutritional management.Psychotic episodes in patients with PA have been infrequently reported . Similar to other inborn errors of metabolism, care should be exercised when using antipsychotic medications as they can mask clinical signs of encephalopathy or cause adverse effects.SurveillanceThe following evaluations are performed at different intervals depending on factors such as age, disease severity, and presence of catabolic stressors; evaluation frequency can range from every three months to annually.Clinical evaluation should include assessment of the following:Linear growth, weight gain, head circumference, and body mass indexInterval assessment for the need of G-tubeNeurologic evaluation including survey for seizures and movement disordersInterval ophthalmologic evaluation including dilated eye examinationAudiology evaluationEvaluation for clinical signs of cardiomyopathy (e.g., tachycardia, tachypnea, shortness of breathy, hepatomegaly)Evaluation of integumentary system | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. can range from every three months to annually.Clinical evaluation should include assessment of the following:Linear growth, weight gain, head circumference, and body mass indexInterval assessment for the need of G-tubeNeurologic evaluation including survey for seizures and movement disordersInterval ophthalmologic evaluation including dilated eye examinationAudiology evaluationEvaluation for clinical signs of cardiomyopathy (e.g., tachycardia, tachypnea, shortness of breathy, hepatomegaly)Evaluation of integumentary system (skin, hair, G-tube, and central line insertion sites)Developmental and neurocognitive progress, as age-appropriateLaboratory evaluation should include the following:Metabolic studies: urine organic acids, pre-prandial plasma amino acids (especially, isoleucine, leucine, valine, threonine, and methionine), plasma ammonia concentration, plasma free and total carnitine, and quantitative plasma acylcarnitine profileNutritional studies: electrolytes, mineral panel, albumin, pre | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. of integumentary system (skin, hair, G-tube, and central line insertion sites)Developmental and neurocognitive progress, as age-appropriateLaboratory evaluation should include the following:Metabolic studies: urine organic acids, pre-prandial plasma amino acids (especially, isoleucine, leucine, valine, threonine, and methionine), plasma ammonia concentration, plasma free and total carnitine, and quantitative plasma acylcarnitine profileNutritional studies: electrolytes, mineral panel, albumin, prealbumin, hemoglobin, vitamin D, iron studies, essential fatty acids, and trace minerals (selenium and zinc)Complete blood count and differential to monitor for cytopeniasRenal function tests; serum cystatin C can be more sensitive than plasma creatinine in identifying early evidence of chronic renal failure.Amylase and lipase as needed to evaluate for pancreatitisOther evaluations:Cardiology evaluation, screening for cardiomyopathy and arrhythmias by echocardiogram, ECG, and Holter monitor, annual and as neededOphthalmologic evaluation to | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. mineral panel, albumin, prealbumin, hemoglobin, vitamin D, iron studies, essential fatty acids, and trace minerals (selenium and zinc)Complete blood count and differential to monitor for cytopeniasRenal function tests; serum cystatin C can be more sensitive than plasma creatinine in identifying early evidence of chronic renal failure.Amylase and lipase as needed to evaluate for pancreatitisOther evaluations:Cardiology evaluation, screening for cardiomyopathy and arrhythmias by echocardiogram, ECG, and Holter monitor, annual and as neededOphthalmologic evaluation to assess optic nerve and retinal changes, annually and as neededDEXA scanBrain MRI, MRS, and EEG as clinically indicatedPhysical, occupational, and speech therapy services to determine needAgents/Circumstances to AvoidAvoid prolonged fasting, catabolic stressors, and excessive protein intake.Lactated Ringer’s solution is not recommended in patients with organic acidemias.In patients with QT abnormalities, avoid medications that can prolong the QT interval.Ondansetron, an antiemetic drug used to control | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. as neededOphthalmologic evaluation to assess optic nerve and retinal changes, annually and as neededDEXA scanBrain MRI, MRS, and EEG as clinically indicatedPhysical, occupational, and speech therapy services to determine needAgents/Circumstances to AvoidAvoid prolonged fasting, catabolic stressors, and excessive protein intake.Lactated Ringer’s solution is not recommended in patients with organic acidemias.In patients with QT abnormalities, avoid medications that can prolong the QT interval.Ondansetron, an antiemetic drug used to control nausea, has been associated with QT interval prolongation on ECG and therefore should be used cautiously in patients with PA who have cardiomyopathy and QT interval abnormalities.Neuroleptic antiemetics (e.g., promethazine) can mask symptoms of progressive encephalopathy and are best avoided.Evaluation of Relatives at RiskTesting of at-risk sibs is warranted to allow for early diagnosis and treatment. If prenatal testing has not been performed on at-risk sibs, measure urine organic | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. an antiemetic drug used to control nausea, has been associated with QT interval prolongation on ECG and therefore should be used cautiously in patients with PA who have cardiomyopathy and QT interval abnormalities.Neuroleptic antiemetics (e.g., promethazine) can mask symptoms of progressive encephalopathy and are best avoided.Evaluation of Relatives at RiskTesting of at-risk sibs is warranted to allow for early diagnosis and treatment. If prenatal testing has not been performed on at-risk sibs, measure urine organic acids, plasma amino acids, and acylcarnitine profile immediately in the newborn period in parallel with newborn screening.See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Pregnancy ManagementAlthough successful pregnancy outcomes have been reported in patients with PA , pregnancy can pose a significant management challenge. Hyperemesis gravidarum may require the use of an antiemetic but the risk of QT interval prolongation and the effect on the central nervous system need to | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. sibs, measure urine organic acids, plasma amino acids, and acylcarnitine profile immediately in the newborn period in parallel with newborn screening.See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Pregnancy ManagementAlthough successful pregnancy outcomes have been reported in patients with PA , pregnancy can pose a significant management challenge. Hyperemesis gravidarum may require the use of an antiemetic but the risk of QT interval prolongation and the effect on the central nervous system need to be considered . Baseline evaluation and monitoring of cardiomyopathy before, during, and after pregnancy is recommended. Reference ranges for total and free plasma carnitine differ during pregnancy . Close nutritional follow up and fetal growth monitoring is necessary as the energy and protein requirements change throughout pregnancy. Close postpartum clinical and biochemical follow up and delayed discharge from the hospital are recommended. In the postpartum period, increased caloric and protein needs during lactation should be taken into consideration.Therapies Under InvestigationSearch ClinicalTrials.gov in the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK92946/ | QE2k7oK | Propionic Acidemia | C0268579 | 31,762 | propionic acidemia. the central nervous system need to be considered . Baseline evaluation and monitoring of cardiomyopathy before, during, and after pregnancy is recommended. Reference ranges for total and free plasma carnitine differ during pregnancy . Close nutritional follow up and fetal growth monitoring is necessary as the energy and protein requirements change throughout pregnancy. Close postpartum clinical and biochemical follow up and delayed discharge from the hospital are recommended. In the postpartum period, increased caloric and protein needs during lactation should be taken into consideration.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. SummaryClinical characteristics.Progressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement in the absence of inflammation. Onset – typically between ages three and six years – begins with the involvement of the interphalangeal joints. Over time, involvement of large joints and the spine causes significant joint contractures, gait disturbance, and scoliosis and/or kyphosis, resulting in abnormal posture and significant morbidity. Despite the considerable arthropathy, pain is not a major presenting feature of this condition. Initially height is normal; however, short stature (<3rd centile) becomes evident in adolescence as the skeletal changes progress.Diagnosis/testing.The diagnosis of PPD is established in a proband with characteristic radiographic features and/or identification of biallelic pathogenic variants in CCN6 (formerly WISP3) on molecular genetic testing.Management.Treatment of manifestations: Treatment is supportive | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. posture and significant morbidity. Despite the considerable arthropathy, pain is not a major presenting feature of this condition. Initially height is normal; however, short stature (<3rd centile) becomes evident in adolescence as the skeletal changes progress.Diagnosis/testing.The diagnosis of PPD is established in a proband with characteristic radiographic features and/or identification of biallelic pathogenic variants in CCN6 (formerly WISP3) on molecular genetic testing.Management.Treatment of manifestations: Treatment is supportive. Pain due to secondary osteoarthritis may respond to nonsteroidal anti-inflammatory drugs. Severe joint pain due to advanced osteoarthritis is treated by joint arthroplasty. Large joint stiffness is managed by physical therapy, activity modification, and walking aids. Small joint arthropathy is managed by an occupational therapist who may advise adaptive devices, modification of activity, and/or vocational training. Scoliosis and mild kyphosis may be treated with bracing. Surgical treatment for angular deformities of the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. testing.Management.Treatment of manifestations: Treatment is supportive. Pain due to secondary osteoarthritis may respond to nonsteroidal anti-inflammatory drugs. Severe joint pain due to advanced osteoarthritis is treated by joint arthroplasty. Large joint stiffness is managed by physical therapy, activity modification, and walking aids. Small joint arthropathy is managed by an occupational therapist who may advise adaptive devices, modification of activity, and/or vocational training. Scoliosis and mild kyphosis may be treated with bracing. Surgical treatment for angular deformities of the lower limbs as per orthopedic surgeon.Surveillance: Monitoring for orthopedic complications including bone deformity, secondary joint disease, spinal deformities, and pain. Annual evaluation by specialist(s) in skeletal dysplasia.Agents/circumstances to avoid: Immobilization (e.g., casting).Pregnancy management: Deformities of the pelvis may necessitate delivery by cæsarean section.Genetic counseling.PPD is inherited in an autosomal recessive manner. If both parents are | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. with bracing. Surgical treatment for angular deformities of the lower limbs as per orthopedic surgeon.Surveillance: Monitoring for orthopedic complications including bone deformity, secondary joint disease, spinal deformities, and pain. Annual evaluation by specialist(s) in skeletal dysplasia.Agents/circumstances to avoid: Immobilization (e.g., casting).Pregnancy management: Deformities of the pelvis may necessitate delivery by cæsarean section.Genetic counseling.PPD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CCN6 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if both CCN6 pathogenic variants have been identified in an affected family member.DiagnosisNo consensus clinical | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CCN6 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if both CCN6 pathogenic variants have been identified in an affected family member.DiagnosisNo consensus clinical diagnostic criteria for progressive pseudorheumatoid dysplasia (PPD) have been published.Suggestive FindingsPPD should be suspected in individuals with the following clinical, laboratory, and radiologic features.Clinical featuresHealthy at birthOnset of arthropathy early in childhood, usually between ages three and six yearsEnlargement of interphalangeal joints of hands (Figure 1)Progressive restricted mobility of all jointsGait abnormalitiesGenu valgu | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. identified in an affected family member.DiagnosisNo consensus clinical diagnostic criteria for progressive pseudorheumatoid dysplasia (PPD) have been published.Suggestive FindingsPPD should be suspected in individuals with the following clinical, laboratory, and radiologic features.Clinical featuresHealthy at birthOnset of arthropathy early in childhood, usually between ages three and six yearsEnlargement of interphalangeal joints of hands (Figure 1)Progressive restricted mobility of all jointsGait abnormalitiesGenu valgum / genu varumProgressive hip disease (commonly coxa vara at the late stage)Articular painMotor weakness and fatigabilitySpine involvement in late childhood and adolescence with thoracolumbar kyphoscoliosis that leads to short trunkAdult height below the third centileAbsence of signs of inflammationFigure 1. Hands of individuals showing progressive swelling and limited range of movement of the interphalangeal joints A. Age 5 yearsLaboratory | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. mobility of all jointsGait abnormalitiesGenu valgum / genu varumProgressive hip disease (commonly coxa vara at the late stage)Articular painMotor weakness and fatigabilitySpine involvement in late childhood and adolescence with thoracolumbar kyphoscoliosis that leads to short trunkAdult height below the third centileAbsence of signs of inflammationFigure 1. Hands of individuals showing progressive swelling and limited range of movement of the interphalangeal joints A. Age 5 yearsLaboratory features include normal erythrocyte sedimentation rate and C-reactive protein levels.Radiologic features include spondyloepiphyseal dysplasia, generalized arthropathy, distinctive joint deformity of the hands (superficially resembling that of juvenile idiopathic arthritis), and diffuse osteoporosis at the late stage.Hands show enlarged epiphyses, widened metaphyses, and loss of or narrow joint spaces in the metacarpophalangeal and interphalangeal joints, particularly in the proximal | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. halangeal joints A. Age 5 yearsLaboratory features include normal erythrocyte sedimentation rate and C-reactive protein levels.Radiologic features include spondyloepiphyseal dysplasia, generalized arthropathy, distinctive joint deformity of the hands (superficially resembling that of juvenile idiopathic arthritis), and diffuse osteoporosis at the late stage.Hands show enlarged epiphyses, widened metaphyses, and loss of or narrow joint spaces in the metacarpophalangeal and interphalangeal joints, particularly in the proximal interphalangeal joints (Figure 2) . Camptodactyly is always present in adulthood.Pelvis. Hips show enlarged and flattened capital femoral epiphyses and short and wide femoral necks (Figure 3) . Broadened ilia and irregular acetabular roofs are observed (Figure 3).Spine. Progressive irregularities in the ossification of vertebral endplates and platyspondyly with loss or narrowing of intervertebral disc spaces are observed | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. eal and interphalangeal joints, particularly in the proximal interphalangeal joints (Figure 2) . Camptodactyly is always present in adulthood.Pelvis. Hips show enlarged and flattened capital femoral epiphyses and short and wide femoral necks (Figure 3) . Broadened ilia and irregular acetabular roofs are observed (Figure 3).Spine. Progressive irregularities in the ossification of vertebral endplates and platyspondyly with loss or narrowing of intervertebral disc spaces are observed in all (Figure 4). Anterior beaking of the vertebral bodies is seen in preadolescents .Shoulders and knees. Osteophytic formations and periarticular calcifications can be seen.Figure 2. Radiographs of hands showing large epiphyses and widened metaphyses of metacarpals and phalanges. Joint space is also reduced. A. Age 5 yearsFigure 3. Pelvic radiographs demonstrating reduced hip joint spaces, large capital femoral epiph | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. yly with loss or narrowing of intervertebral disc spaces are observed in all (Figure 4). Anterior beaking of the vertebral bodies is seen in preadolescents .Shoulders and knees. Osteophytic formations and periarticular calcifications can be seen.Figure 2. Radiographs of hands showing large epiphyses and widened metaphyses of metacarpals and phalanges. Joint space is also reduced. A. Age 5 yearsFigure 3. Pelvic radiographs demonstrating reduced hip joint spaces, large capital femoral epiphyses, short and broad femoral necks, and irregular acetabular roofs. Iliac crests are also irregular in adolescence. A. Age 5 yearsFigure 4. Progressive platyspondyly due to erosion of the superior and inferior articular cartilages A. Age 5 yearsEstablishing the DiagnosisThe diagnosis of PPD can be established in a proband with characteristic radiographic features (see Suggestive Findings) and/or biallelic pathogenic variants in | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. radiographs demonstrating reduced hip joint spaces, large capital femoral epiphyses, short and broad femoral necks, and irregular acetabular roofs. Iliac crests are also irregular in adolescence. A. Age 5 yearsFigure 4. Progressive platyspondyly due to erosion of the superior and inferior articular cartilages A. Age 5 yearsEstablishing the DiagnosisThe diagnosis of PPD can be established in a proband with characteristic radiographic features (see Suggestive Findings) and/or biallelic pathogenic variants in CCN6 (formerly WISP3) identified on molecular genetic testing (Table 1).Note: Identification of biallelic CCN6 variants of uncertain significance (or identification of one known CCN6 pathogenic variant and one CCN6 variant of uncertain significance) does not establish or rule out the diagnosis of this disorder.Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) | [
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] |
gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. Findings) and/or biallelic pathogenic variants in CCN6 (formerly WISP3) identified on molecular genetic testing (Table 1).Note: Identification of biallelic CCN6 variants of uncertain significance (or identification of one known CCN6 pathogenic variant and one CCN6 variant of uncertain significance) does not establish or rule out the diagnosis of this disorder.Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive
genomic testing (exome sequencing, genome sequencing) depending on the phenotype.Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of PPD has not been considered are more likely to be diagnosed using genomic testing (see Option | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. testing (single-gene testing, multigene panel) and comprehensive
genomic testing (exome sequencing, genome sequencing) depending on the phenotype.Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of PPD has not been considered are more likely to be diagnosed using genomic testing (see Option 2).Option 1Single-gene testing. Sequence analysis of CCN6 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by sequence analysis, the next step is to perform gene-targeted deletion | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. more likely to be diagnosed using genomic testing (see Option 2).Option 1Single-gene testing. Sequence analysis of CCN6 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by sequence analysis, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.If only one or no pathogenic variant is found, sequence analysis of cDNA from peripheral blood or cultured skin fibroblasts may be performed to detect splicing aberrations resulting from intronic pathogenic variants (see Molecular Genetics).Targeted analysis for pathogenic variants can include the following:c.156C>A (p.Cys52Ter) is the most frequent pathogenic variant in individuals of Turkish | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. , the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.If only one or no pathogenic variant is found, sequence analysis of cDNA from peripheral blood or cultured skin fibroblasts may be performed to detect splicing aberrations resulting from intronic pathogenic variants (see Molecular Genetics).Targeted analysis for pathogenic variants can include the following:c.156C>A (p.Cys52Ter) is the most frequent pathogenic variant in individuals of Turkish ethnicity and accounts for approximately 28% of pathogenic variants worldwide .c.1010G>A (p.Cys337Tyr) and c.233G>A (p.Cys78Tyr) are the most common pathogenic variants in the Indian population.A multigene panel that includes CCN6 and other genes of interest (see Differential Diagnosis) may also be considered to identify the genetic cause of the condition at | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. ) is the most frequent pathogenic variant in individuals of Turkish ethnicity and accounts for approximately 28% of pathogenic variants worldwide .c.1010G>A (p.Cys337Tyr) and c.233G>A (p.Cys78Tyr) are the most common pathogenic variants in the Indian population.A multigene panel that includes CCN6 and other genes of interest (see Differential Diagnosis) may also be considered to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. be considered to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.Option 2When the diagnosis of PPD has not been | [
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] |
gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. iew. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.Option 2When the diagnosis of PPD has not been considered because an individual has atypical phenotypic features, comprehensive
genomic testing, which does not require the clinician to determine which gene is likely involved, is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.Table 1. Molecular Genetic Testing Used in Progressive Pseudorheumatoid DysplasiaView in own windowGene | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. Option 2When the diagnosis of PPD has not been considered because an individual has atypical phenotypic features, comprehensive
genomic testing, which does not require the clinician to determine which gene is likely involved, is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.Table 1. Molecular Genetic Testing Used in Progressive Pseudorheumatoid DysplasiaView in own windowGene 1MethodProportion of Pathogenic Variants 2 Detectable by MethodCCN6Sequence analysis 3Nearly 100% 4, 5Gene-targeted deletion/duplication analysis 6~1% 71. See Table A. Genes and Databases for chromosome locus and protein.2. See Molecular Genetics for information on variants detected in this gene.3. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. rheumatoid DysplasiaView in own windowGene 1MethodProportion of Pathogenic Variants 2 Detectable by MethodCCN6Sequence analysis 3Nearly 100% 4, 5Gene-targeted deletion/duplication analysis 6~1% 71. See Table A. Genes and Databases for chromosome locus and protein.2. See Molecular Genetics for information on variants detected in this gene.3. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.4. Data derived from the subscription-based professional view of Human Gene Mutation Database 5. Among the pathogenic variants were three intronic variant alleles identified by fibroblast cDNA sequence analysis; two of the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. , likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.4. Data derived from the subscription-based professional view of Human Gene Mutation Database 5. Among the pathogenic variants were three intronic variant alleles identified by fibroblast cDNA sequence analysis; two of the three are deep intronic pathogenic variants . Targeted analysis for these intronic variants or genomic sequencing may also be used.6. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.7. A 9-kb deletion encompassing the 5′ | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. alleles identified by fibroblast cDNA sequence analysis; two of the three are deep intronic pathogenic variants . Targeted analysis for these intronic variants or genomic sequencing may also be used.6. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.7. A 9-kb deletion encompassing the 5′ untranslated region and exon 1 was reported in one family .Clinical CharacteristicsClinical DescriptionProgressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement, and the absence of signs of inflammation . Progression of the disease severely affects gait and posture and causes significant morbidity.PPD does not have any extraskeletal manifestations, such as craniofacial features or cognitive involvement.To date, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. 7. A 9-kb deletion encompassing the 5′ untranslated region and exon 1 was reported in one family .Clinical CharacteristicsClinical DescriptionProgressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement, and the absence of signs of inflammation . Progression of the disease severely affects gait and posture and causes significant morbidity.PPD does not have any extraskeletal manifestations, such as craniofacial features or cognitive involvement.To date, approximately 215 families with members affected with PPD have been identified with biallelic pathogenic variants in CCN6 . The following description of the phenotypic features associated with this condition is based on these reports.Table 2. Progressive Pseudorheumatoid Dysplasia: Frequency of Select FeaturesView in own windowFeature% of Persons with FeatureCommentInterphalangeal joint involvement100%Giving appearance of swollen joints that are painlessLarge joint involvement100 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. such as craniofacial features or cognitive involvement.To date, approximately 215 families with members affected with PPD have been identified with biallelic pathogenic variants in CCN6 . The following description of the phenotypic features associated with this condition is based on these reports.Table 2. Progressive Pseudorheumatoid Dysplasia: Frequency of Select FeaturesView in own windowFeature% of Persons with FeatureCommentInterphalangeal joint involvement100%Giving appearance of swollen joints that are painlessLarge joint involvement100%Typically knees, hips, wrists, & elbowsSpine involvement93%Typically platyspondylyShort stature50%Not all have short stature.Onset. Children with PPD are normal at birth and during infancy. Onset is typically between ages three and six years ; the range of onset age is from one year to 16 years .Initial presenting features in the majority are interphalangeal joint swelling, pain, and gait abnormalities | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. swollen joints that are painlessLarge joint involvement100%Typically knees, hips, wrists, & elbowsSpine involvement93%Typically platyspondylyShort stature50%Not all have short stature.Onset. Children with PPD are normal at birth and during infancy. Onset is typically between ages three and six years ; the range of onset age is from one year to 16 years .Initial presenting features in the majority are interphalangeal joint swelling, pain, and gait abnormalities. Joint deformities become manifest over time. Joint pain is rarely the presenting symptom and is disproportionately mild compared to the severity of arthropathy.Joints. Enlargement, stiffness, and restricted range of movement in the hands start in the proximal interphalangeal joints and progress to the distal interphalangeal joints (Figure 1) . These joints develop progressive contractures.The joint enlargement, stiffness, and restricted range of movement gradually involve all large joints (e. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. interphalangeal joint swelling, pain, and gait abnormalities. Joint deformities become manifest over time. Joint pain is rarely the presenting symptom and is disproportionately mild compared to the severity of arthropathy.Joints. Enlargement, stiffness, and restricted range of movement in the hands start in the proximal interphalangeal joints and progress to the distal interphalangeal joints (Figure 1) . These joints develop progressive contractures.The joint enlargement, stiffness, and restricted range of movement gradually involve all large joints (e.g., knees, hips, wrists, and elbows) . Hip involvement commonly manifests as coxa vara later in the disease course. The knees show either genu varum or genu valgum. Typically, the shoulder joints are not severely affected .Spine. Scoliosis and/or kyphosis are noted in a majority of affected individuals during adolescence. Lordosis may also be seen. The neck is only occasionally involved .Height. Height is initially | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. range of movement gradually involve all large joints (e.g., knees, hips, wrists, and elbows) . Hip involvement commonly manifests as coxa vara later in the disease course. The knees show either genu varum or genu valgum. Typically, the shoulder joints are not severely affected .Spine. Scoliosis and/or kyphosis are noted in a majority of affected individuals during adolescence. Lordosis may also be seen. The neck is only occasionally involved .Height. Height is initially normal; however, short stature becomes evident in some individuals as the skeletal changes progress. Adult height is typically below the third centile . Flexion deformities at the hips and knees as well as spinal changes contribute in part to the short stature.Genotype-Phenotype CorrelationsNo genotype-phenotype correlations have been observed.Mild variation in age of onset, severity, and progression noted in different families is not explained by the type of pathogenic variants or their locations.Intraf | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. neck is only occasionally involved .Height. Height is initially normal; however, short stature becomes evident in some individuals as the skeletal changes progress. Adult height is typically below the third centile . Flexion deformities at the hips and knees as well as spinal changes contribute in part to the short stature.Genotype-Phenotype CorrelationsNo genotype-phenotype correlations have been observed.Mild variation in age of onset, severity, and progression noted in different families is not explained by the type of pathogenic variants or their locations.Intrafamilial variation has been observed .NomenclatureThe name "progressive pseudorheumatoid dysplasia" reflects its resemblance to juvenile rheumatoid arthritis.PPD was previously referred to as "spondyloepiphyseal dysplasia with progressive arthropathy" or "progressive pseudorheumatoid chondrodysplasia."PrevalenceThe prevalence of PPD has been estimated at one per million in the United Kingdom (prevalence category of <1-9:1 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. by the type of pathogenic variants or their locations.Intrafamilial variation has been observed .NomenclatureThe name "progressive pseudorheumatoid dysplasia" reflects its resemblance to juvenile rheumatoid arthritis.PPD was previously referred to as "spondyloepiphyseal dysplasia with progressive arthropathy" or "progressive pseudorheumatoid chondrodysplasia."PrevalenceThe prevalence of PPD has been estimated at one per million in the United Kingdom (prevalence category of <1-9:1,000,000) . However, the disease may be underdiagnosed due to the overlap of clinical features with juvenile idiopathic arthritis. To date more than 215 families with molecularly confirmed PPD have been reported.PPD is more frequent in communities with a high rate of consanguinity . The largest series has been published from India .PPD has also been observed among populations with a high rate of consanguinity in Kuwait, Lebanon, Iran, Jord | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. prevalence category of <1-9:1,000,000) . However, the disease may be underdiagnosed due to the overlap of clinical features with juvenile idiopathic arthritis. To date more than 215 families with molecularly confirmed PPD have been reported.PPD is more frequent in communities with a high rate of consanguinity . The largest series has been published from India .PPD has also been observed among populations with a high rate of consanguinity in Kuwait, Lebanon, Iran, Jordan, Saudi Arabia, Syria, Palestine, and Morocco.Differential DiagnosisJuvenile idiopathic arthritis and all skeletal dysplasias with epiphyseal and spondylar involvement are to be considered in the differential diagnosis of progressive pseudorheumatoid dysplasia (PPD).Juvenile idiopathic arthritis (JIA) is the disorder most commonly confused with PPD. The main differentiating features are:Joint inflammation (tenderness and warmth) in JIAEle | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. Kuwait, Lebanon, Iran, Jordan, Saudi Arabia, Syria, Palestine, and Morocco.Differential DiagnosisJuvenile idiopathic arthritis and all skeletal dysplasias with epiphyseal and spondylar involvement are to be considered in the differential diagnosis of progressive pseudorheumatoid dysplasia (PPD).Juvenile idiopathic arthritis (JIA) is the disorder most commonly confused with PPD. The main differentiating features are:Joint inflammation (tenderness and warmth) in JIAElevation of erythrocyte sedimentation rate and C-reactive protein levels in JIA and not in PPD. However, in some instances elevation of these acute reactants in JIA can be minimal.In JIA, joint destruction is seen on radiographs. In PPD, radiographs show dysplasia along with epiphyseal enlargement and platyspondyly.Skeletal dysplasias with epiphyseal and spondylar involvement. See Table 3.Table 3. Genes of Interest in the Differential Diagnosis of Progressive | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. Joint inflammation (tenderness and warmth) in JIAElevation of erythrocyte sedimentation rate and C-reactive protein levels in JIA and not in PPD. However, in some instances elevation of these acute reactants in JIA can be minimal.In JIA, joint destruction is seen on radiographs. In PPD, radiographs show dysplasia along with epiphyseal enlargement and platyspondyly.Skeletal dysplasias with epiphyseal and spondylar involvement. See Table 3.Table 3. Genes of Interest in the Differential Diagnosis of Progressive Pseudorheumatoid DysplasiaView in own windowGene(s)DiffDx DisorderMOIFeatures of DiffDx DisorderOverlapping w/PPDDistinguishing from PPDCOL2A1Spondyloepimetaphyseal dysplasia, Strudwick type (See Type II Collagen Disorders Overview.)ADSevere disproportionate short stature, platyspondyly, scoliosis, genu valgumPresents in infancy, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. 3. Genes of Interest in the Differential Diagnosis of Progressive Pseudorheumatoid DysplasiaView in own windowGene(s)DiffDx DisorderMOIFeatures of DiffDx DisorderOverlapping w/PPDDistinguishing from PPDCOL2A1Spondyloepimetaphyseal dysplasia, Strudwick type (See Type II Collagen Disorders Overview.)ADSevere disproportionate short stature, platyspondyly, scoliosis, genu valgumPresents in infancy, characteristic flat facial profile, ocular abnormalities, delayed ossification & metaphyseal flaring, absence of large epiphysesCOL2A1Mild spondyloepiphyseal dysplasia with premature-onset arthrosis (See Type II Collagen Disorders Overview.)ADProgressive joint pain & limitation of motion at hips & knees, epiphyseal dysplasia & early-onset osteoarthrosisFlattened, small epiphysesCOL2 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. scoliosis, genu valgumPresents in infancy, characteristic flat facial profile, ocular abnormalities, delayed ossification & metaphyseal flaring, absence of large epiphysesCOL2A1Mild spondyloepiphyseal dysplasia with premature-onset arthrosis (See Type II Collagen Disorders Overview.)ADProgressive joint pain & limitation of motion at hips & knees, epiphyseal dysplasia & early-onset osteoarthrosisFlattened, small epiphysesCOL2A1FN1Spondylometaphyseal dysplasia, corner fracture typeADShort stature, scoliosis, coxa vara, genu varum or valgum, joint painVision impairment, normal epiphysesCOL2A1 1Spondyloepiphyseal dysplasia w/metatarsal shortening (formerly Czech dysplasia) (See Type II Collagen Disorders Overview.)ADEarly-onset osteoarthritis; radiologic features as in PPD: plat | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. rosisFlattened, small epiphysesCOL2A1FN1Spondylometaphyseal dysplasia, corner fracture typeADShort stature, scoliosis, coxa vara, genu varum or valgum, joint painVision impairment, normal epiphysesCOL2A1 1Spondyloepiphyseal dysplasia w/metatarsal shortening (formerly Czech dysplasia) (See Type II Collagen Disorders Overview.)ADEarly-onset osteoarthritis; radiologic features as in PPD: platyspondyly w/irregular endplates & usually anterior-posteriorly elongated vertebral bodies, coxa vara, short femoral neck, & narrow joint spaces)Severe joint pain in lower limbs before adolescence, normal stature, & hypoplastic 3rd, 4th, & 5th toesGALNSGLB1GNSHGSNATIDSIDUANAGLUSGSHMucopolysaccharidoses (e. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. -onset osteoarthritis; radiologic features as in PPD: platyspondyly w/irregular endplates & usually anterior-posteriorly elongated vertebral bodies, coxa vara, short femoral neck, & narrow joint spaces)Severe joint pain in lower limbs before adolescence, normal stature, & hypoplastic 3rd, 4th, & 5th toesGALNSGLB1GNSHGSNATIDSIDUANAGLUSGSHMucopolysaccharidoses (e.g. MPS I, MPS II, MPS III, MPS IVA, & MPS IVB) 2ARXLVertebral deformities (hook-shaped vertebral bodies w/inferior beaking or platyspondyly w/central beaking) & progressive joint limitation similar to those in PPD.Extraskeletal manifestations observed in the MPSs (e.g., coarse facies, corneal clouding, hepatomegaly, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. HMucopolysaccharidoses (e.g. MPS I, MPS II, MPS III, MPS IVA, & MPS IVB) 2ARXLVertebral deformities (hook-shaped vertebral bodies w/inferior beaking or platyspondyly w/central beaking) & progressive joint limitation similar to those in PPD.Extraskeletal manifestations observed in the MPSs (e.g., coarse facies, corneal clouding, hepatomegaly, ID) are not present in PPD.LACC1LACC1-related juvenile arthritis (OMIM 618795)AROnset in childhood, joint deformities, joint contractures, joint pain, joint swellingErosive arthritis, ↑ markers of inflammation. Fever, erythematous rash, generalized lymphadenopathy, & hepatosplenomegaly seen in some personsTRAPPC2X-linked spondyloepiphyseal dysplasia tarda (XL-SED | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. coarse facies, corneal clouding, hepatomegaly, ID) are not present in PPD.LACC1LACC1-related juvenile arthritis (OMIM 618795)AROnset in childhood, joint deformities, joint contractures, joint pain, joint swellingErosive arthritis, ↑ markers of inflammation. Fever, erythematous rash, generalized lymphadenopathy, & hepatosplenomegaly seen in some personsTRAPPC2X-linked spondyloepiphyseal dysplasia tarda (XL-SEDT)XLDevelops in adolescence or adulthood & is assoc w/disproportionate short stature w/short trunk & arm span significantly greater than height. Affected males exhibit linear growth deficiency from age ~6-8 yrs. Progressive joint & back pain w/osteoarthritis; hip, knee, & shoulder joints are commonly involvedInterphalangeal joints are typically spared.AD = autosomal dominant; AR = autosomal recessive; | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. oepiphyseal dysplasia tarda (XL-SEDT)XLDevelops in adolescence or adulthood & is assoc w/disproportionate short stature w/short trunk & arm span significantly greater than height. Affected males exhibit linear growth deficiency from age ~6-8 yrs. Progressive joint & back pain w/osteoarthritis; hip, knee, & shoulder joints are commonly involvedInterphalangeal joints are typically spared.AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; ID = intellectual disability; MOI = mode of inheritance; MPSs = mucopolysaccharidoses; PPD = progressive pseudorheumatoid dysplasia; XL = X-linked1. Czech dysplasia is typically associated with the COL2A1 p.Arg275Cys pathogenic variant.2. See Mucopolysaccharidoses: OMIM Phenotypic Series to view genes associated with this phenotype | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. .AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; ID = intellectual disability; MOI = mode of inheritance; MPSs = mucopolysaccharidoses; PPD = progressive pseudorheumatoid dysplasia; XL = X-linked1. Czech dysplasia is typically associated with the COL2A1 p.Arg275Cys pathogenic variant.2. See Mucopolysaccharidoses: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with progressive pseudorheumatoid dysplasia (PPD), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Progressive Pseudorheumatoid DysplasiaView in own windowSystem/ConcernEvaluationCommentS | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with progressive pseudorheumatoid dysplasia (PPD), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Progressive Pseudorheumatoid DysplasiaView in own windowSystem/ConcernEvaluationCommentSkeletalComplete skeletal surveyReferral to pediatric orthopedic surgeon or specialist in treating bone dysplasiasGeneticcounselingBy genetics professionals 1To inform affected persons & families re nature, MOI, & implications of PPD to facilitate medical & personal decision makingMOI = mode of inheritance; PPD = progressive pseudorheumatoid dysplasia1. Medical geneticist, certified genetic counselor, or certified advanced | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. View in own windowSystem/ConcernEvaluationCommentSkeletalComplete skeletal surveyReferral to pediatric orthopedic surgeon or specialist in treating bone dysplasiasGeneticcounselingBy genetics professionals 1To inform affected persons & families re nature, MOI, & implications of PPD to facilitate medical & personal decision makingMOI = mode of inheritance; PPD = progressive pseudorheumatoid dysplasia1. Medical geneticist, certified genetic counselor, or certified advanced genetic nurseTreatment of ManifestationsTreatment is supportive. No specific therapy for PPD is available.Table 5. Treatment of Manifestations in Individuals with Progressive Pseudorheumatoid DysplasiaView in own windowManifestation/ConcernTreatmentConsiderations/OtherPain due to secondaryosteoarthritisNSAIDs may be helpful.Other anti-inflammatory medications incl steroids & immunosuppressive drugs (cyclosporine & methotrexate) have a limited role | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. geneticist, certified genetic counselor, or certified advanced genetic nurseTreatment of ManifestationsTreatment is supportive. No specific therapy for PPD is available.Table 5. Treatment of Manifestations in Individuals with Progressive Pseudorheumatoid DysplasiaView in own windowManifestation/ConcernTreatmentConsiderations/OtherPain due to secondaryosteoarthritisNSAIDs may be helpful.Other anti-inflammatory medications incl steroids & immunosuppressive drugs (cyclosporine & methotrexate) have a limited role in treatment & are best avoided in view of their significant side effects.Severe joint pain due to advanced osteoarthritis is treated by joint arthroplasty (e.g., hip & knee replacement).Early hip replacement (2nd decade of life) can be successful in relieving pain & restoring ambulation.Progressive jointstiffnessLarge-joint stiffness is managed by PT, activity modification, & walking aids.Small | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. (cyclosporine & methotrexate) have a limited role in treatment & are best avoided in view of their significant side effects.Severe joint pain due to advanced osteoarthritis is treated by joint arthroplasty (e.g., hip & knee replacement).Early hip replacement (2nd decade of life) can be successful in relieving pain & restoring ambulation.Progressive jointstiffnessLarge-joint stiffness is managed by PT, activity modification, & walking aids.Small joint arthropathy is managed by OT, who may advise adaptive devices, modification of activity, &/or vocational training.Immobilization (e.g., casting) should be avoided.Scoliosis & mildkyphosisBracing per pediatric orthopedic surgeon w/expertise in treating bone dysplasiasSpinal canal stenosisDecompression, fusion, & instrumentation per pediatric orthopedic surgeon w/expertise in treating bone dysplasia | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. , activity modification, & walking aids.Small joint arthropathy is managed by OT, who may advise adaptive devices, modification of activity, &/or vocational training.Immobilization (e.g., casting) should be avoided.Scoliosis & mildkyphosisBracing per pediatric orthopedic surgeon w/expertise in treating bone dysplasiasSpinal canal stenosisDecompression, fusion, & instrumentation per pediatric orthopedic surgeon w/expertise in treating bone dysplasiasAngular deformitiesof lower limbsTreatment per pediatric orthopedic surgeon w/expertise in treating bone dysplasiasIndications for surgical correction: to restore normal alignment of lower limbs & alleviate gait disturbance, instability, &/or painNSAIDs = nonsteroidal anti-inflammatory drugs; OT = occupational therapist; PT = physical therapistSurveillanceNo specific guidelines for surveillance have been published.Table 6. Recommended Surveillance for Individuals with | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. per pediatric orthopedic surgeon w/expertise in treating bone dysplasiasAngular deformitiesof lower limbsTreatment per pediatric orthopedic surgeon w/expertise in treating bone dysplasiasIndications for surgical correction: to restore normal alignment of lower limbs & alleviate gait disturbance, instability, &/or painNSAIDs = nonsteroidal anti-inflammatory drugs; OT = occupational therapist; PT = physical therapistSurveillanceNo specific guidelines for surveillance have been published.Table 6. Recommended Surveillance for Individuals with Progressive Pseudorheumatoid DysplasiaView in own windowSystem/ConcernEvaluationFrequencySkeletalMonitor for orthopedic complications incl bone deformity, secondary joint disease, spinal deformities, & pain.At each visitEval by specialist in skeletal dysplasia or multidisciplinary skeletal dysplasia clinicAnnuallyAgents/Circumstances to AvoidAvoid immobilization (e.g., casting).Evaluation of Relatives at RiskSee Genetic Counseling for issues related | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. been published.Table 6. Recommended Surveillance for Individuals with Progressive Pseudorheumatoid DysplasiaView in own windowSystem/ConcernEvaluationFrequencySkeletalMonitor for orthopedic complications incl bone deformity, secondary joint disease, spinal deformities, & pain.At each visitEval by specialist in skeletal dysplasia or multidisciplinary skeletal dysplasia clinicAnnuallyAgents/Circumstances to AvoidAvoid immobilization (e.g., casting).Evaluation of Relatives at RiskSee Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Pregnancy ManagementDeformities of pelvis may necessitate delivery by cæsarean section in pregnant women who have PPD.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK327267/ | JRxXkXX | Progressive Pseudorheumatoid Dysplasia | C0432215 | 31,763 | progressive pseudorheumatoid dysplasia. Evaluation of Relatives at RiskSee Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Pregnancy ManagementDeformities of pelvis may necessitate delivery by cæsarean section in pregnant women who have PPD.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. | [
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medlineplus | https://medlineplus.gov/genetics/condition/nonsyndromic-congenital-nail-disorder-10/ | AVm4Ono | Nonsyndromic congenital nail disorder 10 | null | 31,764 | nonsyndromic congenital nail disorder 10. Nonsyndromic congenital nail disorder 10 is a condition that affects the fingernails and toenails. Affected individuals have extremely thick nails (onychauxis) that separate from the underlying nail bed (onycholysis) and can appear claw-like. Some fingers and toes may be missing part of the nail (hyponychia).In affected individuals, the nails are often abnormal from birth. However, the abnormalities may not be noticeable until later in childhood because the nails tend to grow more slowly than normal.Individuals with nonsyndromic congenital nail disorder 10 do not have any other health problems related to the condition.FrequencyNonsyndromic congenital nail disorder 10 is likely a rare disorder. At least 14 affected individuals have been described in the scientific literature.CausesNonsyndromic congenital nail disorder 10 is caused by mutations in the FZD6 gene, which provides instructions for making a protein called frizzled-6 | [
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medlineplus | https://medlineplus.gov/genetics/condition/nonsyndromic-congenital-nail-disorder-10/ | AVm4Ono | Nonsyndromic congenital nail disorder 10 | null | 31,764 | nonsyndromic congenital nail disorder 10. be noticeable until later in childhood because the nails tend to grow more slowly than normal.Individuals with nonsyndromic congenital nail disorder 10 do not have any other health problems related to the condition.FrequencyNonsyndromic congenital nail disorder 10 is likely a rare disorder. At least 14 affected individuals have been described in the scientific literature.CausesNonsyndromic congenital nail disorder 10 is caused by mutations in the FZD6 gene, which provides instructions for making a protein called frizzled-6. This protein is embedded in the outer membrane of many types of cells, where it is involved in transmitting chemical signals from outside the cell to the cell's nucleus. The frizzled-6 protein plays an especially critical role in the growth and development of nails, particularly the attachment of the nail to the nail bed.FZD6 gene mutations that cause nonsyndromic congenital nail disorder 10 lead to the production of a frizzled-6 protein | [
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medlineplus | https://medlineplus.gov/genetics/condition/nonsyndromic-congenital-nail-disorder-10/ | AVm4Ono | Nonsyndromic congenital nail disorder 10 | null | 31,764 | nonsyndromic congenital nail disorder 10. for making a protein called frizzled-6. This protein is embedded in the outer membrane of many types of cells, where it is involved in transmitting chemical signals from outside the cell to the cell's nucleus. The frizzled-6 protein plays an especially critical role in the growth and development of nails, particularly the attachment of the nail to the nail bed.FZD6 gene mutations that cause nonsyndromic congenital nail disorder 10 lead to the production of a frizzled-6 protein that cannot get to the cell membrane where it is needed or that cannot transmit signals into the cell. As a result, the growth and development of nails is poorly regulated, which leads to onycholysis and other abnormalities of the fingernails and toenails.Learn more about the gene associated with Nonsyndromic congenital nail disorder 10
FZD6
Inheritance PatternThis condition is inherited in an autosomal recessive pattern, which means both copies of the | [
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medlineplus | https://medlineplus.gov/genetics/condition/nonsyndromic-congenital-nail-disorder-10/ | AVm4Ono | Nonsyndromic congenital nail disorder 10 | null | 31,764 | nonsyndromic congenital nail disorder 10. the production of a frizzled-6 protein that cannot get to the cell membrane where it is needed or that cannot transmit signals into the cell. As a result, the growth and development of nails is poorly regulated, which leads to onycholysis and other abnormalities of the fingernails and toenails.Learn more about the gene associated with Nonsyndromic congenital nail disorder 10
FZD6
Inheritance PatternThis condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | [
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] |
omim | https://www.omim.org/entry/224410 | Yw028rn | DYSSEGMENTAL DYSPLASIA, SILVERMAN-HANDMAKER TYPE | C1857100 | 31,765 | dyssegmental dysplasia, silverman-handmaker type. A number sign (#) is used with this entry because the Silverman-Handmaker type of dyssegmental dysplasia (DDSH) is caused by homozygous or compound heterozygous mutation in the gene encoding perlecan (HSPG2; 142461) on chromosome 1p36.See also Schwartz-Jampel syndrome type 1 (SJS1; 255800), an allelic disorder with a less severe but overlapping phenotype.
Clinical Features
The dyssegmental dysplasias are lethal forms of neonatal short-limbed dwarfism. Handmaker et al. (1977) coined the term 'dyssegmental dysplasia' because of the marked differences in size and shape of the vertebral bodies (anisospondyly), which he attributed to errors in segmentation. Fasanelli et al. (1985) proposed that there are different forms of dyssegmental dwarfism, a | [
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omim | https://www.omim.org/entry/224410 | Yw028rn | DYSSEGMENTAL DYSPLASIA, SILVERMAN-HANDMAKER TYPE | C1857100 | 31,765 | dyssegmental dysplasia, silverman-handmaker type. less severe but overlapping phenotype.
Clinical Features
The dyssegmental dysplasias are lethal forms of neonatal short-limbed dwarfism. Handmaker et al. (1977) coined the term 'dyssegmental dysplasia' because of the marked differences in size and shape of the vertebral bodies (anisospondyly), which he attributed to errors in segmentation. Fasanelli et al. (1985) proposed that there are different forms of dyssegmental dwarfism, a lethal Silverman type and a less severe Rolland-Desbuquois type (224400). Aleck et al. (1987) found reports of 18 cases, including 3 reports of affected sibs, and reported 8 additional cases. The authors presented further evidence for the existence of 2 forms of dyssegmental dysplasia.
Molecular Genetics
In a pair of sibs with DDSH born to consanguineous parents | [
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] |
omim | https://www.omim.org/entry/224410 | Yw028rn | DYSSEGMENTAL DYSPLASIA, SILVERMAN-HANDMAKER TYPE | C1857100 | 31,765 | dyssegmental dysplasia, silverman-handmaker type. ) proposed that there are different forms of dyssegmental dwarfism, a lethal Silverman type and a less severe Rolland-Desbuquois type (224400). Aleck et al. (1987) found reports of 18 cases, including 3 reports of affected sibs, and reported 8 additional cases. The authors presented further evidence for the existence of 2 forms of dyssegmental dysplasia.
Molecular Genetics
In a pair of sibs with DDSH born to consanguineous parents, Arikawa-Hirasawa et al. (2001) identified a homozygous 89-bp duplication in exon 34 of the HSPG2 gene (142461.0003). A third unrelated patient was compound heterozygous for 2 truncating mutations (142461.0004; 142461.0005). The cartilage matrix from these patients stained poorly with antibody specific for perlecan, but there was staining of | [
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omim | https://www.omim.org/entry/224410 | Yw028rn | DYSSEGMENTAL DYSPLASIA, SILVERMAN-HANDMAKER TYPE | C1857100 | 31,765 | dyssegmental dysplasia, silverman-handmaker type. Genetics
In a pair of sibs with DDSH born to consanguineous parents, Arikawa-Hirasawa et al. (2001) identified a homozygous 89-bp duplication in exon 34 of the HSPG2 gene (142461.0003). A third unrelated patient was compound heterozygous for 2 truncating mutations (142461.0004; 142461.0005). The cartilage matrix from these patients stained poorly with antibody specific for perlecan, but there was staining of intracellular inclusion bodies. Truncated perlecan was not secreted by patient fibroblasts, but was degraded into smaller fragments within the cells. Thus, the Silverman-Handmaker type of dyssegmental dysplasia is caused by a functional null mutation of HSPG2. Arikawa-Hirasawa et al. (2001) concluded that their findings demonstrate the critical role of perlecan in cartilage development.
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] |
omim | https://www.omim.org/entry/224410 | Yw028rn | DYSSEGMENTAL DYSPLASIA, SILVERMAN-HANDMAKER TYPE | C1857100 | 31,765 | dyssegmental dysplasia, silverman-handmaker type. patients stained poorly with antibody specific for perlecan, but there was staining of intracellular inclusion bodies. Truncated perlecan was not secreted by patient fibroblasts, but was degraded into smaller fragments within the cells. Thus, the Silverman-Handmaker type of dyssegmental dysplasia is caused by a functional null mutation of HSPG2. Arikawa-Hirasawa et al. (2001) concluded that their findings demonstrate the critical role of perlecan in cartilage development.
INHERITANCE
- Autosomal recessive
GROWTH
Other
- Short-limbed dwarfism
HEAD & NECK
Head
- Occipital skull defect
Face
- Flat face
Ears
- Posteriorly rotated ears
Nose
- Wide nasal bridge
Mouth
- Small mouth
- Micrognathia
RESPIRATORY
Lung
- Pulmonary hypoplasia
CHEST
External Features
- Small chest
ABDOMEN
External Features
- Two vessel cord
GENITOURINARY
Internal Genitalia (Male)
- Cryptorchidism
SKELETAL
- Chondroosseous morphology notable for short, irregular chondrocyte columns, | [
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] |
omim | https://www.omim.org/entry/224410 | Yw028rn | DYSSEGMENTAL DYSPLASIA, SILVERMAN-HANDMAKER TYPE | C1857100 | 31,765 | dyssegmental dysplasia, silverman-handmaker type. findings demonstrate the critical role of perlecan in cartilage development.
INHERITANCE
- Autosomal recessive
GROWTH
Other
- Short-limbed dwarfism
HEAD & NECK
Head
- Occipital skull defect
Face
- Flat face
Ears
- Posteriorly rotated ears
Nose
- Wide nasal bridge
Mouth
- Small mouth
- Micrognathia
RESPIRATORY
Lung
- Pulmonary hypoplasia
CHEST
External Features
- Small chest
ABDOMEN
External Features
- Two vessel cord
GENITOURINARY
Internal Genitalia (Male)
- Cryptorchidism
SKELETAL
- Chondroosseous morphology notable for short, irregular chondrocyte columns, large, unfused calcospherites, perichondral bone overgrowth and patchy, mucoid degeneration of resting cartilage
Spine
- Dyssegmental dysplasia
- Anisospondyly
Limbs
- Short, bent long bones
Feet
- Talipes equinovarus
MISCELLANEOUS
- Neonatal lethal
MOLECULAR BASIS
- Caused by mutation in the perlecan gene (HSPG2,
142461.0001
)
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] |
omim | https://www.omim.org/entry/224410 | Yw028rn | DYSSEGMENTAL DYSPLASIA, SILVERMAN-HANDMAKER TYPE | C1857100 | 31,765 | dyssegmental dysplasia, silverman-handmaker type. orchidism
SKELETAL
- Chondroosseous morphology notable for short, irregular chondrocyte columns, large, unfused calcospherites, perichondral bone overgrowth and patchy, mucoid degeneration of resting cartilage
Spine
- Dyssegmental dysplasia
- Anisospondyly
Limbs
- Short, bent long bones
Feet
- Talipes equinovarus
MISCELLANEOUS
- Neonatal lethal
MOLECULAR BASIS
- Caused by mutation in the perlecan gene (HSPG2,
142461.0001
)
▲ Close | [
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omim | https://www.omim.org/entry/269870 | QRVLXQL | SHORT STATURE-OBESITY SYNDROME | C1849235 | 31,766 | short stature-obesity syndrome. Schinzel and Bernasconi (1990) reported the cases of a 13-year-old boy and his 28-year-old sister who had short stature, obesity, and a pattern of minor anomalies including a sloping, narrow forehead; small ears; narrow nose with prominent bridge and long septum; receding mandible; and short limbs with brachydactyly and clinodactyly of the fifth fingers. Intelligence was normal. The parents were normal but remotely consanguineous. Both had hypermetropia. The sister was 138 cm tall and managed the family's butchery. At age 22, the brother had reached the height of 142 cm.
HEENT
- Sloping, narrow forehead
- Small ears
- Narrow nose
- Prominent nasal bridge
- Long nasal septum
- Micrognathia
Limbs
- Short limbs
- Brachydactyly
- Fifth finger clinodactyly
Growth
- Short stature
- Obesity
Inheritance
- Autosomal recessive | [
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omim | https://www.omim.org/entry/269870 | QRVLXQL | SHORT STATURE-OBESITY SYNDROME | C1849235 | 31,766 | short stature-obesity syndrome. were normal but remotely consanguineous. Both had hypermetropia. The sister was 138 cm tall and managed the family's butchery. At age 22, the brother had reached the height of 142 cm.
HEENT
- Sloping, narrow forehead
- Small ears
- Narrow nose
- Prominent nasal bridge
- Long nasal septum
- Micrognathia
Limbs
- Short limbs
- Brachydactyly
- Fifth finger clinodactyly
Growth
- Short stature
- Obesity
Inheritance
- Autosomal recessive
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orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1865 | 8NyA4jZ | Dyssegmental dysplasia, Silverman-Handmaker type | C1857100 | 31,767 | dyssegmental dysplasia, silverman-handmaker type. Dyssegmental dysplasia, Silverman-Handmaker type is a rare, genetic, primary bone dysplasia disorder, and lethal form of neonatal short-limbed dwarfism, characterized by anisospondyly, severe short stature and limb shortening, metaphyseal flaring and distinct dysmorphic features (i.e. flat facial appearance, abnormal ears, short neck, narrow thorax). Additional features may include other skeletal findings (e.g. joint contractures, bowed limbs, talipes equinovarus) and urogenital and cardiovascular abnormalities. | [
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