Clinical Characteristics
Ocular Features
Optic atrophy is seen as early as 5 years of age but may be congenital in origin as hypoplasia of the optic nerve was present in all patients. Three of 4 affected children also were myopic.
Systemic Features
This is a form of mitochondriopathy with considerable clinical heterogeneity. A single consanguineous family with 4 affected children of ages 5-16 years of age has been reported.
Common features include short stature, microcephaly (1 had macrocephaly), hearing impairment. Ataxia, dysmetria, and athetotic movements may be present. Motor and mental development are delayed as is expressive speech. Intellectual disability is present in all 4 patients. Leukoencephalopathy was seen in all patients and one had brain atrophy. Cerebellar hypoplasia was present in 2 of four patients.
Muscle mitochondria in one patient had morphologic changes. Lactate levels and lactate/pyruvate ratios were elevated in the blood and CSF fluid of three patients.
Genetics
Inheritance
Homozygous mutations in the YME1L1 gene (10p12.1) were responsible for this condition in 4 offspring of a consanguineous Saudi Arabian family. This is a nuclear encoded mitochondrial gene.
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.