Basel-Vanagaite-Smirin-Yosef Syndrome
A number sign (#) is used with this entry because of evidence that Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS) is caused by homozygous mutation in the MED25 gene (610197) on chromosome 19q13.
DescriptionBasel-Vanagaite-Smirin-Yosef syndrome is an autosomal recessive multiple congenital anomaly disorder characterized by severely delayed psychomotor development resulting in mental retardation, as well as variable eye, brain, cardiac, and palatal abnormalities (summary by Basel-Vanagaite et al., 2015).
Clinical FeaturesBasel-Vanagaite et al. (2015) reported 7 children from 4 unrelated families living in the same small village in Israel with a severe syndromic neurodevelopmental disorder. All had severely delayed psychomotor development apparent from infancy and variable eye abnormalities, including ptosis, microcornea, and congenital cataracts. Common dysmorphic facial features included epicanthal folds, hypertelorism, short philtrum, wide cupid bow, tented upper lip, everted lower lip vermilion, sparse hair, sparse eyebrows, and nevus flammeus simplex on the forehead. None of the children was able to speak or walk independently, including the oldest, who was 13 years old. Additional features present in most, but not all, patients included cleft palate, cardiac septal defects, hypospadias, hypotonia, thin corpus callosum, cerebral ventricular dilatation, and seizures.
InheritanceThe transmission pattern of BVSYS in the family reported by Basel-Vanagaite et al. (2015) was consistent with autosomal recessive inheritance.
Molecular GeneticsIn 7 children from 4 unrelated families with BVSYS, Basel-Vanagaite et al. (2015) identified a homozygous missense mutation in the MED25 gene (Y39C; 610197.0003). The mutation was found by whole-exome sequencing and segregated with the disorder in all 3 of the families in which segregation analysis was possible. Coimmunoprecipitation studies showed that the mutation impaired MED25 interaction with the Mediator complex in mammalian cells.