TaoMedAI/RareMedData huggingface dataset:
Bilateral multicystic dysplastic kidney (ORPHA:97364)
A rare lethal form of multicystic dysplastic kidney (MCDK), a congenital anomaly of the kidney and urinary tract (CAKUT), in which both kidneys are large, distended by non-communicating multiple cysts and non-functional.
Epidemiology
The prevalence and incidence of bilateral MCDK are unknown.
Clinical description
Bilateral MCDK may be suspected antenatally at routine ultrasound scans, with the majority detected around the 20th week of gestation. It is considered a lethal entity, and most pregnancies are terminated. When born, such infants present with features of the Potter sequence (constellation of signs resulting from prolonged in utero oligohydramnios) including severe pulmonary hypoplasia and severe renal failure, limb anomalies and facial dysmorphic features, and generally die shortly after birth.
Etiology
MCDK results from disrupted nephrogenesis but the exact pathogenic mechanism is still unknown. Disturbed formation of nephrons could result from impaired fetal urine flow early in development. Mutations in the HNF1B gene (17q12), coding for hepatocyte nuclear transcription factor 1beta, are known to cause unilateral MCDK and have only rarely been reported for bilateral cases. MCDK is also linked to gestational diabetes and to the use of some medications during pregnancy, such as anti-epileptic drugs.
Diagnostic methods
Diagnosis is mainly based on prenatal ultrasound showing large hypoechogenic, non-communicating cysts within an irregularly outlined kidney with no visible renal pelvis. A tiny remnant kidney can be observed if the cysts have involuted. In addition, oligo/anhydramnios is present as a sign of poor functional renal development.
Differential diagnosis
Differential diagnoses include bilateral pelviureteric junction obstruction, in which the largely dilated calices may appear to be cysts. Posterior urethral valves may result in oligo/anhydramnios, and the megaureter may be mistaken for renal cysts.
Antenatal diagnosis
Ultrasonographic screening can detect MCDKs from midway through gestation.
Genetic counseling
Both sporadic and familial cases have been observed. In familial cases, transmission is autosomal dominant with a recurrence risk of 50%.
Management and treatment
As the absence of functional renal tissue results in anhydramnios with pulmonary hypoplasia (Potter sequence), which is generally lethal shortly after birth, most pregnancies with bilateral MCDK will be terminated. When children with bilateral MCDK survive the early postnatal period, renal replacement therapy will be needed.
Prognosis
Bilateral MCDK is considered a lethal entity.

                            Last update: 
                            March 2020


                            - Expert reviewer(s): 
                            Pr M.F. [Michiel] SCHREUDER | ERKNet*


                                * European Reference Network
Bilateral polymicrogyria (ORPHA:268940)
Bilateral polymicrogyria is a rare cerebral malformation due to abnormal neuronal migration defined as a cerebral cortex with many excessively small convolutions. It presents with developmental delay, intellectual disability, seizures and various neurological impairments and may be isolated or comprise a clinical feature of many genetic syndromes. It may also be associated with perinatal cytomegalovirus infection.
Bile acid CoA ligase deficiency and defective amidation (ORPHA:276066)
Bile acid CoA ligase deficiency and defective amidation is an anomaly of bile acid synthesis (see this term) characterized by fat malabsorption, neonatal cholestasis and growth failure.
Epidemiology
Prevalence is unknown. Only 8 cases have been reported.
Clinical description
Patients present with a history of neonatal cholestasis, fat and fat-soluble vitamin malabsorption (rickets or bleeding secondary to hypoprothrombinemia) and growth failure.
Etiology
Several mutations in the bile acid-CoA ligase gene have been found in most patients with this defect.
Genetic counseling
The mode of transmission of these mutations is not known.

                            Last update: 
                            January 2011


                            - Expert reviewer(s): 
                            Pr James HEUBI
Biliary atresia with splenic malformation syndrome (ORPHA:244283)
Biliary atresia with splenic malformation syndrome (BASM) designates the association of biliary atresia (see this term) and splenic abnormalities (mainly polysplenia and less frequently asplenia, double spleen). Cardiac defect, situs inversus and a preduodenal portal vein can also be present. It represents the embryonal or syndromic form of biliary atresia. It affects newborns or infants and is characterized by jaundice, pale stools, dark urine, failure to thrive, hepatomegaly, coagulopathy, anemia and often palpable spleen.
Biotin-thiamine-responsive basal ganglia disease (ORPHA:65284)
A rare genetic neurological disorder characterized by subacute encephalopathy with confusion, seizures, and movement disorder, often following a history of febrile illness. Imaging may reveal bilateral lesions in the basal ganglia. The disease usually becomes symptomatic in childhood and is life-threatening if left untreated, but symptoms can be reversed and progression prevented by treatment with high doses of biotin and thiamine.
Bipartite talus (ORPHA:364198)
A rare, genetic bone disorder characterized by the presence of two non-fused talar bone fragments, with the posterior fragment located at the level of the posterior talar process. Patients may present with foot and/or ankle pain (exercise-induced or not), repetitive ankle sprains, chronic ankle ligamentous laxity, restricted ankle motion (i.e. plantar flexion, eversion, and inversion), and mild swelling.
Björnstad syndrome (ORPHA:123)
Björnstad syndrome is characterized by congenital sensorineural hearing loss and pili torti.
Epidemiology
Less than fifty cases have been reported so far.
Clinical description
The hearing loss usually becomes evident very early in life, often in the first year. Pili torti, a condition in which the hair shaft is flattened and twisted, makes the hair very brittle and patients develop hair loss in the first two years of life.
Etiology
Björnstad syndrome is caused by mutations in the BCS1L gene. Mutations in this gene also cause GRACILE syndrome (see this term).
Genetic counseling
Björnstad syndrome is transmitted as an autosomal recessive condition.

                            Last update: 
                            September 2007


                            - Expert reviewer(s): 
                            Dr Pascal REYGAGNE
Blake pouch cyst (ORPHA:98922)
Blake pouch cyst is a non-syndromic, usually benign, cystic malformation of the posterior fossa characterized by a midline outpouching of the superior medullary velum into the cisterna magna that results from failure of the rudimental fourth ventricular tela choroidea to regress during embryogenesis. Patients can be asymptomatic or present in childhood or adulthood with clinical manifestations of hydrocephalus, such as headache, hypotonia, vertigo, syncope, vomiting, blurred or double vision, nystagmus, papilledema, and delayed gait development.
Bleeding diathesis due to a collagen receptor defect (ORPHA:73271)
A rare, genetic coagulation disorder characterized by a mild to moderate bleeding tendency due to impaired platelet activation and aggregation in response to collagen, or impaired platelet-vessel wall interaction, resulting from a collagen receptor defect. Patients manifest with ecchymoses, epistaxis, menorrhagia, and/or post-traumatic and post-surgery bleeding complications. Laboratory analysis reveals prolonged bleeding time and, occasionally, mild thrombocytopenia.
Bleeding diathesis due to thromboxane synthesis deficiency (ORPHA:220443)
A rare, genetic, isolated constitutional thrombocytopenia disease characterized by impaired platelet aggregation resulting from a defect in thromboxane synthesis or signaling, manifesting with mild to moderate mucocutaneous, gastrointestinal or surgical bleeding (e.g. easy bruising, prolonged epistaxis, excessive bleeding after a tooth extraction).
Bleeding disorder due to CalDAG-GEFI deficiency (ORPHA:420566)
Bleeding disorder due to CalDAG-GEFI deficiency is a rare hematologic disease due to defective platelet function and characterized by mucocutaneous bleeding starting in infancy (around 18 months of age), presenting with prolonged and severe epistaxis, hematomas and bleeding after tooth extraction. Massive menorrhagia and chronic anemia have also been reported.
Bleeding disorder due to P2Y12 defect (ORPHA:36355)
P2Y12 defect is a rare hemorrhagic disorder characterized by mild to moderate bleeding diathesis with easy bruising, mucosal bleedings, and excessive post-operative hemorrhage due to defect of the platelet P2Y12 receptor resulting in selective impairment of platelet responses to adenosine diphosphate.
Epidemiology
To date, 14 patients have been described in the world literature.
Clinical description
P2Y12 defect is a congenital disorder that manifests by mildly to severely prolonged bleeding time, easy bruising, mucosal bleeding (epistaxis, gastric mucosa bleeding, gum bleeding, etc.), menorrhagia, and bleeding complications after trauma and minor or major surgery.
Etiology
P2Y12 defect is caused by mutations in the  P2RY12 gene (3q24-q25) which result in the premature truncation of the P2Y12 receptor or in the synthesis of a dysfunctional P2Y12 receptor. ADP activates platelets through its interaction with two G protein-coupled receptors, P2Y1 and P2Y12. The P2Y1 receptor mediates mobilization of ionized calcium and is responsible for ADP-induced shape change andweak and transient aggregation, while the P2Y12 receptor is responsible for the completion and amplification of the response to ADP and to all platelet agonists including thromboxane A2, thrombin, and collagen. P2Y12 receptor thus plays a central role in the formation and stabilization of a thrombus.
Genetic counseling
Transmission of P2Y12 deficiency is autosomal recessive. Genetic counseling should be offered to at-risk couples (where both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child.

                            Last update: 
                            January 2014


                            - Expert reviewer(s): 
                            Pr Marco CATTANEO
Bleeding disorder in hemophilia A carriers (ORPHA:177926)
A rare bleeding disorder in association with carrier mutations in the F8 gene (Xq28) encoding coagulation factor VIII (FVIII), with a biological activity of FVIII ≥40 IU/dL and characterized clinically by abnormal bleeding as a result of minor injuries or following trauma, surgery or tooth extraction. Spontaneous hemorrhages may occur occasionally. Heavy menstrual bleeding is the most frequent type of bleed in the carriers.
Bleeding disorder in hemophilia B carriers (ORPHA:177929)
A rare bleeding disorder in association with carrier mutations in the F9 gene (Xq27.1) encoding coagulation factor IX (FIX), with a biological activity of FIX ≥40 IU/dL and characterized clinically by abnormal bleeding as a result of minor injuries or following trauma, surgery or tooth extraction. Spontaneous hemorrhages may occur occasionally. Heavy menstrual bleeding is the most frequent type of bleed in the carriers.
Blepharonasofacial malformation syndrome (ORPHA:1252)
Blepharonasofacial syndrome is a rare otorhinolaryngological malformation syndrome characterized by a distinctive mask-like facial dysmorphism, lacrimal duct obstruction, extrapyramidal features, digital malformations and intellectual disability.
Epidemiology
Blepharonasofacial syndrome has been reported in 3 families to date.
Clinical description
The facies has a mask-like appearance due to weakness of facial muscles, and lacrimal duct obstruction is characteristic. Clinical features also include telecanthus (with temporal displacement of lacrimal puncta), bulky nose, broad nasal bridge, sometimes a hypoplastic midface, longitudinal cheek furrows, trapezoidal upper lip and malformation of the ears. Intellectual disability, cutaneous syndactyly, torsion dystonia, increased deep tendon reflexes, Babinski sign, poor coordination, and joint laxity are also observed.
Etiology
Inheritance is thought to be either autosomal or X-linked dominant.

                            Last update: 
                            January 2014
Blepharophimosis-intellectual disability syndrome, MKB type (ORPHA:293707)
A rare, X-linked, syndromic, intellectual disability disorder affecting only boys and characterized by global development delay with little or no speech, urogenital abnormalities, including scrotal hypoplasia, micro penis, and cryptorchidism, autistic behavior, and facial dysmorphism. Most typical facial features are ptosis, blepharophimosis, a bulbous nasal tip, a long philtrum, and maxillar hypoplasia with full cheeks. Other variable features include microcephaly, hearing loss, dental anomalies, and hyperextensible joints.
Blepharophimosis-intellectual disability syndrome, Ohdo type (ORPHA:2728)
A multiple congenital malformation syndrome characterized by blepharophimosis, ptosis, dental hypoplasia, hearing impairment and intellectual disability.
Epidemiology
So far, less than 30 patients have been reported worldwide.
Clinical description
Abnormal ears, microcephaly, and growth retardation have been reported occasionally. Male patients may show cryptorchidism and scrotal hypoplasia.
Genetic counseling
Most reported cases are sporadic, except the original cases of Ohdo who described two affected sisters and a first cousin, favoring autosomal recessive inheritance. Autosomal dominant, X-linked- and mitochondrial inheritance have also been suggested.

                            Last update: 
                            May 2009
Blepharophimosis-intellectual disability syndrome, Verloes type (ORPHA:293725)
A rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by congenital microcephaly, severe epilepsy with hypsarrhythmia, adducted thumbs, abnormal genitalia, and normal thyroid function. Hypotonia, moderate to severe psychomotor delay, and characteristic facial dysmorphism (including round face with prominent cheeks, blepharophimosis, large, bulbous nose with wide alae nasi, posteriorly rotated ears with dysplastic conchae, narrow mouth, cleft palate, and mild micrognathia) are additional characteristic features.
Blepharophimosis-intellectual disability syndrome/genitopatellar overlap syndrome (ORPHA:597746)
A rare developmental defect during embryogenesis characterized by the presence of major features of both blepharophimosis-intellectual disability syndrome and genitopatellar syndrome. These major features may include blepharophimosis, ptosis, hypomimia, skeletal features like patellar a/hypoplasia and renal and/or genital malformations.
Blepharophimosis-ptosis-epicanthus inversus syndrome plus (ORPHA:572333)
A rare disorder of the ocular adnexa characterized by an extended phenotype of blepharophimosis, ptosis, epicanthus inversus and telechantus syndrome (BPES). When BPES is caused by a microdeletion encompassing other genes in addition to the causative gene FOXL2, the patient has additional features including intellectual disability, external genital anomaly, spastic diplegia, and speech delay. Acquired microcephaly can also be observed.
Blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome (ORPHA:2057)
A rare syndrome characterised by the association of blepharophimosis and ptosis, V-esotropia, and weakness of extraocular and frontal muscles with syndactyly of the toes, short stature, prognathism, and hypertrophy and fusion of the eyebrows.
Blepharoptosis-myopia-ectopia lentis syndrome (ORPHA:1259)
A rare, genetic, lens position anomaly disease characterized by bilateral congenital blepharoptosis, ectopia lentis and high grade myopia. Additional reported manifestations include abnormally long eye globes and signs of levator aponeurosis disinsertion. There have been no further descriptions in the literature since 1982.
Blepharospasm-oromandibular dystonia syndrome (ORPHA:93964)
A focal dystonia involving symmetrical benign essential blepharospasm (BEB) and oromandibular dystonia.
Blindness-scoliosis-arachnodactyly syndrome (ORPHA:171844)
This syndrome associates progressive visual loss with scoliosis or kyphoscoliosis and arachnodactyly of the fingers and toes.
Epidemiology
The syndrome has been described in four patients (three males and one female) from the same family.
Clinical description
The male patients presented with the complete phenotype while the female patient suffered only from blindness.
Etiology
No mutations were found in the FBN1, TGFBR1 and TGFBR2 genes which are associated with other syndromes presenting similar clinical findings (i.e. Marfan syndrome; see this term).
Genetic counseling
Transmission seems autosomal dominant.

                            Last update: 
                            October 2009
Blomstrand lethal chondrodysplasia (ORPHA:50945)
Blomstrand lethal chondrodysplasia (BLC) is a neonatal osteosclerotic dysplasia characterized by advanced endochondral bone maturation, very short limbs, dwarfism and prenatal lethality.
Epidemiology
To date, less than 10 cases have been described in the literature.
Clinical description
BLC is a congenital disorder characterized by a low birth weight, facial dysmorphism (widely spaced and protruding eyes (which typically show cataract), depressed nasal bridge, short columella, long philtrum, macroglossia, protruding tongue, severe micrognathia), short trunk, narrow thorax and severe rhizo-meso-acromelic shortness of the limbs. Other anomalies also observed include tooth and mammary gland development defects, hypoplastic lungs, aorta coarctation, and bowel malrotation. Two forms of BCL, have been described: type I which is the severe, classical form and type II which has less severe features (such as absence of short trunk or, severely shortened arms but moderately shortened legs).
Etiology
BLC is caused by inactivating homozygous or compound heterozygous mutations in PTH1R (3p22-p21.1) which encodes the parathyroid hormone (PTH)/parathyroid-hormone-related peptide (PTHrP) receptor (PTH1R). These mutations result in the decrease in binding or response to PTH and PTHrP.
Diagnostic methods
Diagnosis is based on the clinical and radiological characteristics which show generalized increase in bone density with advanced ossification, severe shortness of the long bones with wide metaphyses and club-shaped distal ends, long narrow thorax, calcified hyoid bone and laryngeal cartilage and underdeveloped viscerocranium. Histopathological examination shows an important acceleration of the endochondral ossification in tubular bones, narrow cartilages of the epiphyses and large epiphyseal ossification centers. Diagnosis is confirmed by the genetic screening of PTH1R.
Differential diagnosis
Differential diagnosis includes primary failure of tooth eruption (see this term) and other lethal short limbed dwarfisms.
Antenatal diagnosis
Prenatal diagnosis is achieved by sonographic examination showing polyhydramnios, hydrops fetalis and a fetus with very short limbs, nuchal edema, macroglossia, a protuberant abdomen, internal anomalies and markedly advanced endochondral bone formation.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child.
Prognosis
Both forms of BLC are lethal either prenatally or shortly after birth.

                            Last update: 
                            November 2014


                            - Expert reviewer(s): 
                            Pr Harald JÜPPNER  - Dr Caroline SILVE
Blount disease (ORPHA:2768)
Blount disease is characterized by disturbed growth of the inner portion of the upper tibial extremity, progressively leading to bowlegged deformity with bone angulation just below the knee (tibia varus). In 60% of cases, the condition affects both legs.
Epidemiology
Prevalence is unknown.
Clinical description
Clinically, patients with Blount disease present with bowing and length discrepancy in the lower limbs and a medial prominence of the proximal tibia. Obesity and early walking are predisposing factors for the development of the disorder.
Etiology
The underlying causes are controversial: it seems to be a multifactorial disease, but the contribution of genetic factors is unknown.
Diagnostic methods
Blount disease can only be diagnosed in children over 2 years of age, as tibia varus can occur physiologically.
Management and treatment
A severe untreated deformity can lead to early degenerative arthritis of the knee. Management must be adapted to each child: an orthopaedic therapeutic program is often the first management option, but in more severe cases associated with pain, surgery may be indicated to correct the deformity.

                            Last update: 
                            October 2006


                            - Expert reviewer(s): 
                            Dr Martine LE MERRER
Blue cone monochromatism (ORPHA:16)
Blue cone monochromatism (BCM) is a recessive X-linked disease characterized by severely impaired color discrimination, low visual acuity, nystagmus, and photophobia, due to dysfunction of the red (L) and green (M) cone photoreceptors. BCM is as an incomplete form of achromatopsia (see this term).
Epidemiology
The prevalence is estimated to be 1/100,000 worldwide.
Clinical description
BCM manifests in early infancy and predominantly affects males, with severely impaired color vision and low visual acuity (only rod and blue cone function is preserved). Additionally, photophobia, myopia, and pendular nystagmus are commonly observed. Nystagmus may wane with time.
Etiology
The disorder is caused by mutations in the red and green opsin gene cluster OPN1LW and OPN1MW (Xq28) and thus affect the corresponding cones. These mutations include deletions of the locus control region that is critical for expression of both genes. These deletions may also extend to parts of or the whole opsin gene cluster. Genomic rearrangements (unequal crossing-over) can result in single red and/or red/green hybrid genes carrying deleterious point mutations. The c.607T>C p.C203R missense mutation is commonly observed, but other missense and nonsense mutations have also been reported.
Diagnostic methods
The diagnosis of BCM is achieved by clinical ophthalmological examination, electrophysiological (i.e. electroretinography/ ERG) and psychophysical testing (i.e. color vision, dark adaptometry), where BCM patients show no response to red and green light but normal response to blue light. Mutation screening can confirm the diagnosis.
Differential diagnosis
Differential diagnosis includes achromatopsia, Leber congenital amaurosis, various types of cone dystrophies (see these terms) and cerebral achromatopsia.
Antenatal diagnosis
Prenatal diagnosis may be offered by specialized laboratories for at-risk couples. The use of prenatal diagnostic testing in BCM will vary depending on national customs and ethics.
Genetic counseling
BCM is inherited in an X-linked manner. Genetic counseling is mandatory. A carrier female has a 50% risk of transmitting the mutated allele to her offspring. Penetrance is complete with little variability in disease expression.
Management and treatment
There is no specific therapy available. Management is symptomatic and includes regular ophthalmological follow-up examinations. Patients should be informed about the possibility of using filtering glasses or contact lenses (red tinted or brown) to reduce photophobia and to improve contrast sensitivity. Low-vision aids include high-powered magnifiers for reading.
Prognosis
BCM is usually a stationary disease, yet in rare cases, macular degeneration can occur in older patients.

                            Last update: 
                            August 2013


                            - Expert reviewer(s): 
                            Dr Susanne KOHL