Myopathy, Mitochondrial Anomalies, and Ataxia
Patient Information
Characteristics
Background and History
This is an inherited abnormality of nervous system development. Mitochondria, located inside cells, are often referred to as energy factories and they may be dysfunctional as well. There is widespread dysfunction of the nervous system.
Clinical Correlations
Short stature and delayed nervous system with unsteadiness (ataxia) are seen from early childhood. Patients may never walk and speech is often absent. Muscles are weak and infants may appear “floppy”. Patients often have some intellectual disability. The face appears elongated and facial muscles can appear frozen. The lower jaw can be underdeveloped or enlarged while the palate is highly arched. Some sensory (touch) deficits can be present and there may be random purposeless movements of the digits and limbs, including a tremor. Behavioral abnormalities including anxiety, depression, and schizophrenia have been reported.
The eyes appear small and deeply set. The retina may have abnormal pigmentation and the optic nerves may be pale suggesting impaired visual function but visual acuities have not been reported.
Genetics
Inheritance
Three families have been reported. In two families genetic and pedigree studies suggest autosomal dominant inheritance in which the risk to additional sibs is 50%. In the remaining family the gene mutation in both members of a specific gene are changed (mutated) consistent with autosomal recessive inheritance where the parents (presumably carrying a single mutation) have a 25% chance that each of their children would inherit this condition.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
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.
Diagnosis and Prognosis
This disorder likely has its onset prenatally although the evidence for neurological disease is likely subtle at birth. Neurologists, pediatricians, and ophthalmologists should collaborate in the diagnosis. As there is no single biochemical test that is useful to make the diagnosis ultimately genetic studies to identify the mutation is the only useful method to make the diagnosis.
No treatment has been reported. Physical and speech therapy may be beneficial.
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