Congenital Hypomyelinating Polyneuropathy (HPN, 3 variants) – Golden Retriever

Congenital Hypomyelinating Polyneuropathy (HPN) is an inherited neurological disorder that primarily affects the peripheral nervous system. It is the canine variant of n Charcot-Marie-Tooth Neuropathy occurring in humans. It is characterized by abnormal development or insufficient formation of myelin sheet, which is a protective covering around nerve fibers. Myelin is essential for the proper transmission of nerve signals, and without it, nerve function is impaired.

In Golden Retrievers there are currently three mutations found in different genes that cause HPN. These are probably all inherited in an autosomal dominant way. The mutations that are tested for are found in the myelin protein zero (MPZ) gene, the myotubulin-related protein 2 (MTMR2) gene and the SH3 domain and tetratricopeptide repeats 2  gene (SH3TC2).

All three mutations (MTMR2, MPZ, SH3TC2) lead to similar symptoms: muscle weakness, ataxia, tremors, hypotonia (low muscle tone), and delayed motor development. The severity and progression of these symptoms can vary; MPZ mutations may lead to more severe muscle wasting or atrophy over time, while SH3TC2 and MTMR2 mutations tend to primarily cause weakness and coordination problems without significant muscle wasting.

The mutations can present early in life, often between 2 to 6 months of age. However, signs can sometimes be detected in younger puppies, particularly if the symptoms are more severe.