Mental Retardation X-linked with Cerebellar Hypoplasia and Distinct Facial Appearance is an extremely rare syndrome of cerebellar dysgenesis characterized by intellectual disability, cerebellar anomalies, and distinct facial features. Affected male patients present with moderate to severe intellectual disability, major language and behavioral problems, and impairment in adaptive behavior. The distinct facial phenotype includes a long face, prominent forehead, deep-set eyes, prominent supraorbital ridges, marked infraorbital creases, strabismus, short or upturned philtrum, prognathism, and large ears. There is severe developmental delay and hypotonia, sometimes associated with early-onset complex partial or tonic-clonic seizures in nearly half of the patients. Patients may also show strabismus, dysmetria, and occasionally, ataxia. Brain findings include posterior vermis dysgenesis, vermian parasagittal cleft, cerebellar hypoplasia, cortical atrophy, and enlargement of the cerebral ventricles. Affected females have a milder version of the condition, with mild learning difficulties and congnitive impairment, strabismus, and subtle facial features. Some females may show a reduced cerebellar size.
The condition is diagnosed based on the clinical features. Other X-linked forms of mental retardation may also be associated with similar features. Therefore, a confirmatory diagnosis can only be made on the basis of molecular testing. The condition is managed using speech, occupational, and/or physical therapy. There is a potential for the use of gene therapy, especially targeted towards Rho Kinase inhibitors. However, these therapies are in very early stages of development.
