OMIM ID:
Leukodystrophy, Hypomyelinating, 15
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Severe optic atrophy with marked vision loss is commonly present. Hypermetropia and nystagmus have also been reported.
Systemic Features
The clinical features of 4 unrelated patients are highly variable. Onset of clinical signs is also variable and most are progressive. Several patients have presented in the first month of life with microcephaly and delayed motor development. Progressive cerebellar signs of ataxia with dystonia, dysphagia and motor signs from infancy has been seen. Other patients with cognitive deterioration and progressive neurologic deficits may present late in the first decade of life at which time ataxia, dysarthria, spasticity, and pyramidal signs nay also be noted. Dystonic and athetoid movements and intention tremor have been reported in some patients.
Brain MRIs in older individuals in the second decade of life reveal hypomyelinating leukodystrophy with thinning of the corpus callosum and cerebellar atrophy.
Genetics
Inheritance
Homozygous or compound heterozygous mutations in the EPRS (1q41) gene are responsible for this autosomal recessive disorder.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.