OMIM ID:
Encephalopathy Due To Defective Mitochondrial And Peroxisomal Fission 2
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Visual impairment and optic atrophy are usually present. Visual-evoked potentials may be negative or slowed severely. Some degree of ophthalmoparesis is often present while frank external ophthalmoplegia can develop in the second year of life. In one patient aged 7 years, MRI showed increased T2 signals in the optic radiation.
Systemic Features
Microcephaly becomes evident in the first year of life and seizures can appear in this period as well. General developmental delays are present. There may be evidence of Leigh-like basal ganglia disease. Dysphagia may require the placement of a gastroscopy tube. Truncal hypotonia can be so severe that sitting and head control are not possible. However, there is often spasticity and hyperreflexia in the limbs. EEG recordings show hypsarrhythmia.
Brain MRI may show increased T2 signaling in the global pallidus, thalamus, and the subthalamic nucleus.
Patients may never be able to sit or walk and usually do not develop speech.
Genetics
Inheritance
Homozygous or compound heterozygous truncating mutations in the MFF gene (mitochondrial fission factor) (2q36.3) is responsible for this condition. Patients with EMPF2 may have abnormally elongated and tubular mitochondria and peroxisomes in fibroblasts.
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.