Epilepsy, Hearing Loss, And Mental Retardation Syndrome

A number sign (#) is used with this entry because of evidence that epilepsy, hearing loss, and mental retardation syndrome (EHLMRS) is caused by homozygous or compound heterozygous mutation in the SPATA5 gene (613940) on chromosome 4q28.

Description

Epilepsy, hearing loss, and mental retardation syndrome is an autosomal recessive disorder characterized by severe neurologic impairment including intellectual disability, intractable epilepsy, microcephaly, abnormal muscle tone, and sensorineural hearing loss. Most affected individuals are nonambulatory, cannot sit unassisted, and have no speech development. More variable features include feeding difficulties, poor growth, cortical visual impairment, spasticity, scoliosis, immunodeficiency, and thrombocytopenia (summary by Tanaka et al., 2015).

Clinical Features

Tanaka et al. (2015) reported 14 children from 10 families with a severe neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, microcephaly, and seizures. The patients ranged in age from 2 to 19 years. All patients had abnormal electroencephalograms (EEGs), and all but 1 had tonic-clonic, myoclonic, and/or absence seizures. Twelve patients had hypotonia, 3 had hypertonia, and 7 had spasticity. Most were nonambulatory, could not sit unsupported, and were nonverbal. Vision was variably impaired in all patients; 7 had cortical visual impairment. All patients also had sensorineural hearing impairment. Microcephaly was observed in at least 12 individuals, including 4 with congenital microcephaly and 4 with acquired microcephaly. Brain MRI was abnormal in 7 patients, showing variable diffuse atrophy, cortical atrophy, thin corpus callosum, and hypomyelination. Three patients had thrombocytopenia and 4 had immunodeficiency. Muscle biopsy of 2 patients was suggestive of a possible mitochondrial disorder.

Inheritance

The transmission pattern of EHLMRS in the families reported by Tanaka et al. (2015) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 14 children from 10 families with epilepsy, hearing loss, and mental retardation syndrome, Tanaka et al. (2015) identified homozygous or compound heterozygous mutations in the SPATA5 gene (see, e.g., 613940.0001-613940.0005). The mutations were found by whole-exome sequencing and segregated with the disorder in the families. Functional studies of the variants were not performed.