OMIM ID:
Muscular Dystrophy, Congenital, with Cataracts and Intellectual Disability
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Cataracts have been diagnosed by 6 months of age and may be congenital in origin. Several patients have had strabismus.
Systemic Features
Progressive muscle weakness begins in early childhood. Hypotonia is usually present at birth followed by atrophy of the proximal muscles (especially in the lower limbs). Muscle weakness progresses for several years and may stabilize but not before severe gait difficulties occur. Most adult patients are confined to a wheelchair. No cardiac involvement occurs although respiratory weakness is often present. Serum creatine kinase is usually elevated and biopsied muscle fibers show dystrophic changes and increased variability in fiber size with vacuolization.
Other signs in some individuals are contractures, scoliosis, seizures, short stature, cognitive deficits (usually mild), and spinal rigidity. Paradoxically, some patients have limb spasticity and hyperreflexia with pyramidal signs. No cerebellar signs are present.
Genetics
Inheritance
This condition results from homozygous or compound heterozygous mutations in the INPP5K gene (17p13).
See Marinesco-Sjogren Syndrome for a disorder with a somewhat similar clinical presentation plus cerebellar signs. It is caused by a different mutation, however.
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.