ZTTK Syndrome

A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of developmental delay, intellectual disability and mild to moderate facial dysmorphism in association with variable brain malformations including abnormal gyration patterns, ventriculomegaly, white matter abnormalities, hypoplasia of the corpus callosum and cerebellar hemispheres. Musculoskeletal abnormalities include hemivertebrae, scoliosis or kyphosis, contractures, and joint laxity. Ocular involvement includes strabismus, hypermetropia and cortical visual impairment. Hypotonia may also be associated. Additional clinical manifestations may include seizures, short stature urogenital malformations, heart defects and gastrointestinal malformations. The disorder is due to a heterozygous de novo SON mutation (21q22.11), which encodes for a protein required for proper RNA splicing. Whilst the disease is autosomal dominant, all reported cases have occurred sporadically.