TaoMedAI/RareMedData huggingface dataset:
8p23.1 microdeletion syndrome (ORPHA:251071)
8p23.1 deletion involves a partial deletion of the short arm of chromosome 8 characterized by low birth weight, postnatal growth deficiency, mild intellectual deficit, hyperactivity, craniofacial abnormalities, and congenital heart defects.
Epidemiology
The prevalence is unknown but 8p23.1 deletions are rare. To date, over 50 cases of interstitial or terminal 8p23.1 have been reported without a notable gender discrepancy.
Clinical description
The clinical manifestations are variable and do not depend on the size of the deletion, since this is the same in the majority of patients. Most common manifestations include prenatal and postnatal growth retardation, low birth weight, mild to moderate intellectual deficit, psychomotor retardation, poor speech, seizures, behavioral problems such as hyperactivity and impulsiveness. Frequent craniofacial abnormalities include microcephaly, high and narrow forehead, broad nasal bridge, epicanthic folds, high arched palate, short neck and low set unusually shaped ears. Furthermore congenital heart defects (atrioventricular, septal defects, pulmonary stenosis), congenital diaphragmatic hernia and in boys cryptorchidism and hypospadias have been frequently reported. Some affected individuals have been reported to have normal intelligence.
Etiology
The 8p23.1 deletion is likely to arise through non-allelic homologous recombination mediated by flanking low-copy repeats (LCRs), explaing the common size of approximately 3.4 Mb. The congenital heart defects and diaphragmatic hernia are most likely explained by haploinsufficiency for GATA4.
Diagnostic methods
Diagnosis is based on clinical manifestations leading to chromosomal analysis. 8p23.1 deletions are often missed by standard karyotyping, and mostly detected by molecular karyotyping. Molecular techniques may be used for the genetic characterization of the deletion (FISH, MLPA, aCGH).
Differential diagnosis
Differential diagnosis includes monosomy 22q11 (velocardiofacial syndrome; see this term). Accurate chromosomal analysis confirms the differential diagnosis.
Antenatal diagnosis
Prenatal diagnosis is possible by amniocentesis or chorionic villus sampling and molecular cytogenetic analysis.
Genetic counseling
Genetic counseling is recommended. Most 8p23.1 deletions occur de novo. However, parents can carry and transmit the chromosomal rearrangement to their children as well, with a risk of 50% for each child.
Management and treatment
Management involves assessment, treatment and a regular follow-up by appropriate specialists, including a general practitioner, pediatrician and cardiologists. Early diagnosis and access to major developmental therapies aiming at obtaining the best developmental outcome have been proven beneficial.
Prognosis
Life expectancy is considered normal provided that there is no major congenital heart anomaly or a diaphragmatic hernia.

                            Last update: 
                            December 2012


                            - Expert reviewer(s): 
                            Pr Koenraad DEVRIENDT
8q12 microduplication syndrome (ORPHA:228399)
The newly described 8q12 microduplication syndrome is associated with unusual and characteristic multi-organ clinical features, which include hearing loss, congenital heart defects, intellectual disability, hypotonia in infancy, and Duane anomaly (see this term).
Epidemiology
It has been described in two patients.
Clinical description
The mild facial dysmorphism is characterized by high, arched eyebrows and unilateral narrowing of the palpebral fissure and retraction of the globe caused by Duane anomaly (Duane anomaly is a form of complex strabismus characterized by limited ocular abduction and variably limited adduction accompanied by retraction of the globe, which narrows the palpebral fissure).
Etiology
This microduplication was identified by microarray-based comparative genomic hybridization (aCGH). The lack of recurrent breakpoints in these two cases and the absence of any low-copy repeats (LCR) pairs that flank these de novo events do not support non-allelic homologous recombination as the mutation mechanism. The 8q12 region includes CHD7 and it is proposed that this gene, associated with CHARGE syndrome by haploinsufficiency, causes a different phenotype by gain-of-dosage.

                            Last update: 
                            May 2010


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
8q22.1 microdeletion syndrome (ORPHA:178303)
The 8q22.1 microdeletion syndrome or Nablus mask-like facial syndrome is a rare microdeletion syndrome associated with a distinct facial appearance.
Epidemiology
It has been reported in four unrelated patients.
Clinical description
A mask-like facial appearance is the most characteristic feature with blepharophimosis, tight appearing glistening facial skin, flat and broad nose, dysplastic ears and unusual scalp hair pattern. Camptodactyly, joint contractures, unusual dentition and mild developmental delay can be observed. Cryptorchidism in boys and a happy disposition are constant.
Etiology
This microdeletion was identified by comparative genomic hybridisation (CGH) microarray.

                            Last update: 
                            October 2010


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
8q24.3 microdeletion syndrome (ORPHA:508488)
A multiple congenital anomalies/dysmorphic - intellectual disability syndrome characterized by feeding problems, growth retardation, microcephaly, developmental delay, digital and vertebral anomalies, joint laxity/dislocation, cardiac and renal defects, and dysmorphic facial features (including plagiocephaly, prominent forehead, bitemporal narrowing, bilateral coloboma, epicanthal folds, malformations of the outer and middle ear, wide nasal bridge, anteverted nares, prominent and bulbous nose tip, long philtrum, thin lips, high and narrow palate, micrognathia with prognathism/retrognathism, full cheeks, and short, broad neck). Additional variable manifestations include obstructive apneas, recurrent pneumonia, and seizures.
9p13 microdeletion syndrome (ORPHA:324313)
9p13 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from a partial interstitial deletion of the short arm of chromosome 9, characterized by mild to moderate developmental delay, hand tremors, myoclonic jerks, attention deficit-hyperactivity disorder and a social personality. Patients also present bruxism, short stature and minor facial dysmorphic features (e.g., bilateral epicantic folds, broad, flat nasal bridge, anteverted nares, low-set ears micro/retro-gnathia).
9q21.13 microdeletion syndrome (ORPHA:531151)
A rare, genetic, intellectual disability malformation syndrome characterized by global developmental delay, intellectual disability, delayed speech and language development, epilepsy, autistic behavior, and moderate facial dysmorphism (including elongated face, narrow forehead, arched eyebrows, horizontal palpebral fissures, hypertelorism, epicanthus, midface flattening, short nose, long and featureless philtrum, thin upper lip, macrostomia, and prominent chin). Additional variable manifestations include microcephaly, hypotonia, hypertrichosis, and strabismus.
9q31.1q31.3 microdeletion syndrome (ORPHA:401923)
9q31.1q31.3 microdeletion syndrome is a rare, genetic, syndromic intellectual disability characterized by mild intellectual disability, short stature with high body mass index, short neck with cervical gibbus and dysmorphic facial features. A metabolic syndrome, including type 2 diabetes, hypercholesterolemia and hypertension has also been reported.
9q33.3q34.11 microdeletion syndrome (ORPHA:495818)
A partial monosomy of the long arm of chromosome 9 characterized by intellectual disability, developmental delay with pronounced speech delay, short stature, and muscular hypotonia. Common craniofacial dysmorphic features consist of microcephaly, prominent forehead, round face, arched eyebrows, upslanting palpebral fissures, strabismus, short nose, and thin upper lip. Other clinical findings include epilepsy, ataxia, unspecific brain MRI findings, early-onset primary dystonia, nail dysplasia, and bone malformations, in particular patellar abnormalities, epistaxis, and cutaneous-mucous telangiectasias.
AApoAI amyloidosis (ORPHA:93560)
A rare, hereditary amyloidosis with primary renal involvement characterized by renal interstitial and medullary deposition of amyloid, low plasma levels of ApoA-1 and slow disease progression. Main clinical signs and symptoms are hypertension, proteinuria, hematuria and edema due to chronic renal insufficiency leading to end stage renal disease. Hepatosplenomegaly, progressive cardiomyopathy and involvement of skin, testes and adrenals (hypergonadotropic hypogonadism) have also been reported.
AApoAII amyloidosis (ORPHA:238269)
A rare hereditary amyloidosis with primary renal involvement characterized by variable onset of renal insufficiency with edema, hypertension, proteinuria, and azotemia, eventually leading to end-stage renal disease. Amyloid cardiomyopathy and histopathological evidence of amyloid deposition in other organs, such as the spleen, liver, adrenal glands, and pancreas, among others, have also been described.
AApoAIV amyloidosis (ORPHA:439232)
A rare nonhereditary systemic amyloidosis characterized by slowly progressive renal dysfunction, increased serum creatinine, mostly normal urine analysis with no significant proteinuria and associated heart disease. Cardiac involvement presents as hypertrophic obstructive cardiomyopathy, left ventricular outflow tract obstruction, coronary artery disease and conduction system abnormalities. Histology reveals medullar amyloid deposits, renal tubular atrophy, interstitial fibrosis, and glomerular sclerosis.
Aase-Smith syndrome (ORPHA:916)
A very rare genetic disorder characterised by the following congenital malformations: hydrocephalus (due to Dandy-Walker anomaly), cleft palate, and severe joint contractures.
Epidemiology
Less than 20 cases have been reported in the literature.
Clinical description
The fingers are thin with absent knuckles and reduced creases over the joints, and patients show an inability to make a full fist. Additional findings may include deformed ears, ptosis, an inability to open the mouth fully, heart defects, and clubfoot.
Etiology
The aetiology remains unknown. There are currently no human genes associated with this disease.
Diagnostic methods
The features of the hand are especially important for the diagnosis.
Differential diagnosis
Clinical overlap between Aase-Smith syndrome I and Gordon syndrome (see this term) has been suggested, due to the presence of distal arthrogryposis and cleft palate in both syndromes.
Genetic counseling
Autosomal dominant inheritance is suggested.
Management and treatment
In the absence of a specific treatment, supportive care and surgical correction should be offered.

                            Last update: 
                            July 2007
ABeta amyloidosis, Arctic type (ORPHA:324723)
A form of hereditary cerebral hemorrhage with amyloidosis characterized by an age of onset of 54-61 years and progressive Alzheimer's disease-like dementia. This subtype is due to a mutation in the APP gene (21q21.2), encoding the beta-amyloid precursor protein. This mutation causes an increased accumulation of amyloid-beta protein in the walls of the arteries and capillaries of the meninges, cerebellar cortex and cerebral cortex, leading to the weakening and eventual rupture of these vessels.
ABeta amyloidosis, Dutch type (ORPHA:100006)
A form of hereditary cerebral hemorrhage with amyloidosis characterized by severe cerebral amyloid angiopathy (CAA), predominantly hemorrhagic strokes and dementia.
Epidemiology
The prevalence is unknown. It has been seen in three Dutch families, that are most likely related (before 17th century), to date. Approximately 200-300 patients are known to be affected.
Clinical description
HCHWA-D presents with hemorrhagic stroke between the ages of 39-76 years (average age 50 years). In one third of cases, the initial stroke is fatal, recurrent strokes are seen in those who survive and patients often suffer from serious disability. Cognitive decline can be a presenting symptom in some cases but often occurs after the initial or recurrent strokes. Dementia is seen in the majority of patients with HCHWA-D over the age of 40. Epilepsy is also seen in half of patients who have already experienced a previous stroke.
Etiology
HCHWA-D is due to a mutation in the APP gene on chromosome 21q21.2, encoding the beta-amyloid precursor protein. The mutation leads to extensive amyloid-beta deposition in the meningocortical arterioles, causing them to weaken and rupture.
Diagnostic methods
The diagnosis is clear when a patient presents with a lobar hemorrhage and is known to come from an affected family. Imaging studies show diffuse white matter damage as well as hemorrhages. Genetic testing reveals a mutation in the APP gene.
Differential diagnosis
Differential diagnoses include other conditions that could cause intracerebral hemorrhage such as coagulopathies, vasculitis (see these terms), CNS neoplasms, cerebral vascular malformations, ischemic stroke and antecedent trauma.
Antenatal diagnosis
Antenatal diagnosis is possible but is rarely performed.
Genetic counseling
As HCHWA-D is inherited autosomal dominantly, genetic counseling is possible when a family member is diagnosed with the disease. Pre-symptomatic genetic testing is possible.
Management and treatment
There is currently no acute or preventive treatment for HCHWA-D. Symptomatic treatment (with corticosteroids and antiepileptic drugs) can be given. On pragmatic grounds, antihypertensive treatment is recommended for those with mild to moderate hypertension.
Prognosis
The prognosis is poor. HCHWA-D is often fatal, either acutely at first presentation or, on average, 10 years after symptom onset and after multiple strokes.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Joost HAAN  - Pr G.M. [Gisela] TERWINDT
ABeta amyloidosis, Iowa type (ORPHA:324708)
A form of hereditary cerebral hemorrhage with amyloidosis characterized by age of onset between 50-66 years of age, memory impairment, myoclonic jerks, expressive dysphagia, short-stepped gait, personality changes, and lobar intracerebral hemorrhages. This subtype is due to a mutation in the APP gene (21q21.2), encoding the beta-amyloid precursor protein. This mutation causes an increased accumulation of amyloid-beta protein in the walls of the arteries and capillaries of the meninges, cerebellar cortex and cerebral cortex, leading to the weakening and eventual rupture of these vessels.
ABeta amyloidosis, Italian type (ORPHA:324713)
A form of hereditary cerebral hemorrhage with amyloidosis characterized by an age of onset of 50 years of age, dementia and lobar intracerebral hemorrhage. This subtype is due to a mutation in the APP gene (21q21.2), encoding the beta-amyloid precursor protein. This mutation causes an increased accumulation of amyloid-beta protein in the walls of the arteries and capillaries of the meninges, cerebellar cortex and cerebral cortex, leading to the weakening and eventual rupture of these vessels.
ABetaA21G amyloidosis (ORPHA:324718)
A form of hereditary cerebral hemorrhage with amyloidosis characterized by an age of onset of 45 years of age, progressive Alzheimer's disease-like dementia, and lobar intracerebral hemorrhage in some patients. This subtype is due to a mutation in the APP gene (21q21.2), encoding the beta-amyloid precursor protein. This mutation causes an increased accumulation of amyloid-beta protein in the walls of the arteries and capillaries of the meninges, cerebellar cortex and cerebral cortex, leading to the weakening and eventual rupture of these vessels.
ABetaL34V amyloidosis (ORPHA:324703)
A form of hereditary cerebral hemorrhage with amyloidosis characterized by an age of onset between 50-70 years of age, recurrent lobar intracerebral hemorrhages and cognitive decline. This subtype is due to a mutation in the APP gene (21q21.2), encoding the beta-amyloid precursor protein. This mutation causes an increased accumulation of amyloid-beta protein in the walls of the arteries and capillaries of the meninges, cerebellar cortex and cerebral cortex, leading to the weakening and eventual rupture of these vessels.
Abetalipoproteinemia (ORPHA:14)
A severe, familial hypobetalipoproteinemia characterized by permanently low levels (below the 5th percentile) of apolipoprotein B and LDL cholesterol, and by growth delay, malabsorption, hepatomegaly, and neurological and neuromuscular manifestations.
Epidemiology
It is very rare, with an estimated prevalence of less than 1/1,000,000.
Clinical description
Abetalipoproteinemia manifests during the first year of life or in young childhood. It is often associated with growth delay, hepatomegaly with steatosis, diarrhea with steatorrhea, and fat malabsorption. Spastic ataxia, atypical retinitis pigmentosa, acanthocytosis, a low level of liposoluble vitamins, and major cytolysis and even cirrhosis can occur.
Etiology
Abetalipoproteinemia is a result of mutations of two alleles of the MTTP gene (MTP; 4q24). Other severe early familial hypobetalipoproteinemias are inherited in a codominant manner and are a result of mutations of two alleles of the APOB gene (2p24-p23).
Diagnostic methods
Diagnosis is based on lipid analysis, after 12 hours of fasting, carried out on the patient and their parents to measure serum levels of LDL (<0.10g/L), triglycerides (<0.20 g/L), and apolipoprotein B (<0.10g/L). Identification of steatorrhea and truncated apolipoprotein B after oral lipid intake, measurement of liposoluble vitamins (A, E, K), testing for acanthocytosis (on blood smears), complete neurological examination, hepatic ultrasound and eye examination can also be carried out. Identification of mutations of the MTTP or APOB genes confirms the diagnosis.
Differential diagnosis
Differential diagnoses include metabolic diseases with hepatic overload, with steatosis and/or hepatomegaly, atypical diseases of the central and peripheral nervous system, and secondary causes of hypocholesterolemia (iatrogenic or systemic).
Antenatal diagnosis
Prenatal diagnosis is possible when the causal mutations in both parents are known.
Genetic counseling
Abetalipoproteinemia is inherited in a recessive manner.
Management and treatment
Management should be undertaken in specialized centers.
Prognosis
The prognosis is severe, with a significantly reduced life expectancy.

                            Last update: 
                            May 2009


                            - Expert reviewer(s): 
                            Dr Pascale BENLIAN
Ablepharon macrostomia syndrome (ORPHA:920)
An extremely rare multiple congenital malformation syndrome characterized by the association of ablepharon, macrostomia, abnormal external ears, syndactyly of the hands and feet, skin findings (such as dry and coarse skin or redundant folds of skin), absent or sparse hair, genital malformations and developmental delay (in 2/3 of cases). Other reported manifestations include malar hypoplasia, absent or hypoplastic nipples, umbilical abnormalities and growth retardation. It is a mainly sporadic disorder, although a few familial cases having been reported, and it displays significant clinical overlap with Fraser syndrome.
Abnormal number of coronary ostia (ORPHA:99089)
A rare, congenital, non-syndromic heart malformation characterized by more or less than one coronary ostium at the left and at the right aortic sinus of Valsalva. It may be asymptomatic or it leads to myocardial ischemia and technical difficulties during coronary angiography.
ABri amyloidosis (ORPHA:97345)
A rare, neurodegenerative disease characterized by progressive cognitive impairment, spastic tetraparesis, and cerebellar ataxia resulting from amyloid deposits in the brain. Spasticity with increased deep tendon reflexes and tone are early symptoms, muscular rigidity evolves later. Progressive mental deterioration usually starts with apathy and impaired memory with progression to complete disorientation.
Abruzzo-Erickson syndrome (ORPHA:921)
An orofacial clefting syndrome that is characterized by a cleft palate, ocular coloboma, hypospadias, mixed conductive-sensorineural hearing loss, short stature, and radio-ulnar synostosis.
Epidemiology
To date, 4 cases from a single family have been described in the literature.
Clinical description
Abruzzo-Erickson syndrome is a congenital disorder characterized by a cleft palate, ocular coloboma, hypospadias, mixed conductive-sensorineural hearing loss, short stature, and radio-ulnar synostosis. Additional features include ear malformation, a wide gap between the second and third metacarpals, ulnar deviation, facial asymmetry, dental abnormalities and congenital heart malformation (such as interauricular communication). These manifestations overlap with those of CHARGE syndrome, however, in contrast to CHARGE syndrome; patients with Abruzzo-Erickson syndrome do not show intellectual disability nor choanal atresia or genital hypoplasia.
Etiology
The complete etiology of Abruzzo-Erickson syndrome is still unknown but the recent identification of a novel mutation in the gene TBX22 (Xq21.1) (a gene known to cause X-linked cleft palate and ankyloglossia (CPX) co-segregating in the family strongly indicates that it is a mutation partially responsible for the phenotypic variation.
Diagnostic methods
Diagnosis is based upon clinical observations. Genetic and molecular testing allow to complete the diagnosis.
Differential diagnosis
Differential diagnosis include CHARGE syndrome.
Antenatal diagnosis
Antenatal diagnosis is theoretically possible by DNA analysis of fetal cells in maternal blood.
Genetic counseling
Abruzzo-Erickson syndrome is inherited in an X-linked recessive manner, with a carrier female having a 50 % risk of transmitting the mutation to her offspring.
Management and treatment
Correction of some abnormalities require extensive multidisciplinary craniofacial surgery.
Prognosis
Life expectancy seems normal based on long-term observations of three affected individuals in the family.

                            Last update: 
                            April 2019


                            - Expert reviewer(s): 
                            Dr Michael ABRUZZO  - Dr Robert ERICKSON
Absence deformity of leg-cataract syndrome (ORPHA:2310)
A very rare congenital limb malformation syndrome characterized by absence deformity of one leg, progressive scoliosis, short stature, and congenital cataract associated with dysplasia of the optic nerve. No intellectual deficit has been reported. There have been no further descriptions in the literature since 1968.
Absence of fingerprints-congenital milia syndrome (ORPHA:1658)
A rare syndrome characterized by neonatal blisters and milia (small white papules, especially on the face) and congenital absence of dermatoglyphics on the hands and feet. It has been reported in two kindreds (one of which contained 13 affected individuals spanning three generations) and in an unrelated individual. Some affected patients also showed bilateral partial flexion contractures of the fingers and toes, and webbing of the toes. The syndrome is inherited as an autosomal dominant trait.
Absence of innominate vein (ORPHA:99112)
A rare congenital anomaly of the great veins characterized by absence of the left brachiocephalic vein (or innominate vein), resulting in an anomalous venous vasculature. Patients are usually asymptomatic and the anomaly is typically discovered intraoperatively. An association with persistence of left superior vena cava, permanent levoatrial cardinal vein or anomaly of the inferior vena cava has been reported in some cases.