MMDS4 is a hereditary form of progressive neurological regression recently reported in 5 families.
Abnormal neurological function is evident by about 6 months of age. Infants never achieve normal milestones such as sitting and head-holding and, in fact, regress with increasing disability. Spasticity sets in and muscles become stiff. Brain imaging shows widespread and diffusely abnormal electrical activity. Examination of muscle biopsies reveals nonspecific degenerative changes.
There are no evident physical abnormalities externally. The majority of children do not live beyond the age of 5 years.
Changes (mutations) in both members of a specific pair of genes are required to cause this disorder. Parents with a single mutation are clinically normal. However, when two such parents have children there is a 25% risk for each child to inherit the condition.
The gene product is important to the assembly and function of cellular organelles known as mitochondria which are an important source of energy for cellular operations.
Because there are no external signs such as deformities, there is no reason to suspect any disease at birth. However, within several months when the child fails to develop normally or seems abnormally slow, a neurologist may be able to identify a problem. However, no findings necessarily point to the specific diagnosis and gene studies are necessary to confirm the specific problem.
No treatment is available and supportive care is the only help available.