OMIM ID:
Leukodystrophy, Hypomyelinating, 13
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Several individuals in one family have been observed with optic atrophy, nystagmus and visual impairment.
Systemic Features
Head circumference is normal at birth but later in childhood falls behind in growth. Neurodevelopment seems to plateau without regression. Feeding difficulties may be present from birth and may require gastroscopy tube placement. Motor skills are delayed and expressive language may never develop. General irritability and increased muscle tone with hyperreflexia are usually present eventually resulting in joint contractures.
EEGs , electromyography, and nerve conduction studies have been normal in 3 patients. A brain MRI in one patient showed a leukodystrophic pattern in periventricular areas. Variable cardiac malfunctions such as heart failure, LVH, and pericarditis were observed in several patients.
Sudden death following a short febrile illness has been reported to occur in three of the six affected children before the age of 15 years.
Genetics
Inheritance
Homozygous mutations in the C11ORF73 gene (11q14.2) are responsible for this disorder. Three unrelated families of Ashkenazi Jewish descent have been reported.
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.