Clinical Characteristics
Ocular Features
Nystagmus with optic atrophy is usually present and one individual had glaucoma.
Systemic Features
This is an early-onset and progressive neurodegenerative disorder. Hypotonia may be present at birth. A spastic gait and difficulty walking is noted in early childhood and most individuals never walk unassisted. Yong adults have spastic paresis with extensor plantar responses and clonus has been reported. Distal muscle atrophy in the lower extremities has been noted. Speech is dysarthric. Brain imaging has been normal in some patients whereas others have mild atrophy of the cerebellum and the corpus callosum. Cognitive impairment is variable with some individuals showing poor school performance while others are described as mentally retarded.
Genetics
Inheritance
Homozygous mutations in the MAG gene (19q13.12) are responsible for this 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.