Pelizaeus-Merzbacher Disease, Connatal Form

The connatal form of Pelizaeus-Merzbacher disease (PMD) is the most severe form of PMD (see this term).

Epidemiology

PMD has an estimated prevalence of 1/400,000. The connatal form accounts for approximately 10 to 15 % of all cases of PMD. It predominantly affects males.

Clinical description

Connatal PMD presents, from birth, with hypotonia, nystagmus, respiratory distress, stridor, feeding difficulties and sometimes seizures. Subsequently, there is profound motor and cognitive delay and spastic quadriparesis. Patients never learn to walk, have limited language skills and usually die from respiratory complications by the second decade.

Etiology

The connatal form of PMD is due to missense mutations of the PLP1 gene (on Xq22) that cause hypomyelination of the central nervous system with profound myelin loss. PLP1 encodes the proteolipid protein (PLP), the most abundant protein of the myelin sheath in the central nervous system, and its alternatively spliced isoform (DM20).

Genetic counseling

The disease has an X-linked inheritance pattern.