Null Syndrome

The null syndrome is part of the Pelizaeus-Merzbacher disease (PMD; see this term) spectrum and is characterized by mild PMD features associated with demyelinating peripheral neuropathy.

Epidemiology

Its prevalence is unknown. It predominantly affects males.

Clinical description

The disease manifests during childhood. Patients may have mild developmental delay, delayed sitting and walking beginning usually in the first 2 to 3 years of life, later associated with mild peripheral neuropathy, mild spastic quadriparesis, hyperreflexia, Babinski signs, ataxia, and/or mild intellectual deficit. Patients do not have nystagmus. Although they usually are ambulatory during childhood and have good speech, patients with the null syndrome tend to decline more rapidly beginning in adolescence or early adulthood compared to patients with other PMD forms.

Etiology

The syndrome is due to null mutations of the PLP1 gene (on Xq22) that cause hypomyelination of the central nervous system. 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.