Chudley-McCullough Syndrome (CMCS) is an autosomal recessive disorder caused by variants in GPSM2 encoding G protein signaling modulator 2. This condition is characterized by a distinctive clinical phenotype that includes early-onset profound sensorineural hearing loss and agenesis of the corpus callosum, among other brain malformations. Seizures, while not commonly associated, have been reported.
Hearing loss may be congenital or rapidly progressive leading to severe or profound deafness by age 3 years. Psychomotor development is normal in most, but mild developmental delay has been observed. When hearing loss is managed early, most patients have minor or no impairment of motor and cognitive development, despite the presence of brain malformations. Results of imaging studies can include hypoplasia and/or partial agenesis of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia, polymicrogyria among others. Presentation of hydrocephalus or ventriculomegaly are variable.
Birth prevalence is unknown. The inheritance pattern is autosomal recessive with variants in the GPSM2 gene. Many reported cases are the offspring of consanguineous unions. No genotype to phenotype correlation currently exists, e.g. the presence and/or severity of brain malformations cannot be predicted.
GPSM2