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Basel-Vanagaite-Smirin-Yosef syndrome
Disease definition
A rare, genetic intellectual disability syndrome characterized by severe global developmental delay with intellectual disability, microcephaly, growth retardation, ocular defects such as congenital cataract, and nevus flammeus simplex on the forehead. Cardiac, urogenital, and skeletal abnormalities, as well as seizures are present in most patients. Dysmorphic craniofacial features include sparse hair, downslanting palpebral fissures, hypertelorism, broad and overhanging nasal tip and short philtrum, among others.
ORPHA:464738
Classification level: Disorder- Synonym(s): -
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal, Antenatal
- ICD-10: Q87.8
- OMIM: 616449
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
Summary
Epidemiology
To date, 22 patients have been described with common clinical features and biallelic variants in MED25.
Clinical description
Patients present with some common clinical features. From infancy, almost all have severe global developmental delay with inability to walk and speech, and is followed by intellectual disability (ID). Dysmorphic craniofacial features include sparse hair, high forehead, high frontal hairline, sparse eyebrows, epicanthus, hypertelorism, broad and overhanging nasal tip, short philtrum, exaggerated cupid's bow, retrognathia/micrognathia and nevus flammeus simplex of the forehead. Microcephaly, short stature and feeding difficulties are also reported in some patients, and mandibular prognathia has been reported in various adult individuals from the same family. Other common features that have been described and include 2-3 toe syndactyly, congenital heart diseases (septal defects), urogenital and ocular anomalies (cataract, microcornea, microphthalmia), hypotonia and seizures. Cleft palate, hearing loss, hypospadias, kyphosis / scoliosis, camptodactyly, adducted thumb, tapered fingers with ulnar deviation, overlapping fingers / toes and hyperconvex nails have been described more rarely. Brain imaging abnormalities such as thin corpus callosum, ventriculomegaly and cerebral atrophy are common. Polymicrogyria has recently been reported as a distinctive neuro-radiological finding.
Etiology
The syndrome is caused by homozygous variants in the MED25 gene (19q13.33), coding for a component of the mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes.
Diagnostic methods
Diagnosis is based on clinical examination, brain imaging, cytogenetic and molecular studies.
Differential diagnosis
Differential diagnosis include other genetic syndromes characterized by intellectual disability accompanied by eye and brain abnormalities.
Antenatal diagnosis
Prenatal diagnosis is possible where a known pathogenic variant has previously been identified in a family member.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing variant) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
Management requires a lifelong multidisciplinary approach and includes physical, occupational and speech therapy, in particular non-verbal methods of communication. Treatment is symptomatic and supportive. Antiepileptic drugs may be used to control seizures. Particular attention should be paid to monitoring feeding and growth, particularly as feeding problems tend to occur early on.
Prognosis
Some adult patients are reported; however, current data is limited with regard to life expectancy. Prognosis depends on disease severity.
A summary on this disease is available in Español (2020) Français (2020) Nederlands (2020)
Additional information