OMIM ID:
Multiple Mitochondrial Dysfunctions Syndrome 4
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Optic atrophy is the sole ocular sign reported.
Systemic Features
Patients have the onset of severe, unrelenting neuroregression by 6 months of age. They never achieve normal milestones and eventually regress to a vegetative state. No dysmorphic features are present. Muscle spasticity has been reported. Brain imaging shows multiple nonspecific signal anomalies throughout. Biopsy of skeletal muscle shows atrophic and angulated fibers.
Mitochondrial DNA copy numbers are decreased as is the activity of respiratory complex I.
Genetics
Inheritance
Homozygous mutations in the ISCA2 gene (14q24.3) segregates with the disease in the 5 reported families. This gene codes for an essential component of mitochondrial assembly and function.
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.