OMIM ID:
Charcot-Marie-Tooth Disease with Glaucoma
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Optic atrophy can be an ocular manifestation of CMT disease, especially in the X-linked forms, but this variant is the only one in which early-onset glaucoma is a feature. It may begin at birth in some patients who have features of congenital glaucoma such as buphthalmos, while in other family members, including juveniles, only elevated intraocular pressures were reported. Optic nerve damage seems to occur rapidly.
Systemic Features
This is a sensorineural disease of myelination that causes a polyneuropathy with muscular weakness and sensory deficits. CMT4B2 is characterized by abnormal myelin sheath folding. Symptoms of lower limb weakness and evidence of muscle atrophy commonly appear in the middle of the first decade with progression to upper limb involvement. Areflexia follows with development of pes cavus and hammertoes. Motor nerve conduction velocities may be severely reduced and muscle biopsies show severe loss of myelinated fibers and focal myelin sheath folding.
Genetics
Inheritance
This seems to be an autosomal recessive disorder although only a few families have been reported. Homozygous mutations in the SBF2 gene (sometimes called MTMR13) (11p15.4) were found in these CMT families with early-onset glaucoma (604563). This gene codes for SET binding factor 2 important to the normal development of the trabecular meshwork. Not all SBF2 mutations cause glaucoma though. Of course, it is possible that the occurrence of glaucoma is incidental and not part of CMT4B2 at all.
A clinically similar neurological condition without glaucoma, CMT4B1 (601382), has been reported to be caused by a mutation in MTMR2 located at 11q22 (601382).
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.