Phenotypic Variability Leads to Under-recognition of HNPP

Area of Science:

• Neurology
• Genetics
• Clinical Medicine

Background:

• Hereditary neuropathy with liability to pressure palsy (HNPP) is a genetic disorder.
• A common cause of HNPP is a deletion on chromosome 17.
• Phenotypic variability can complicate diagnosis.

Purpose of the Study:

• To define the spectrum of clinical presentations in HNPP patients with the chromosome 17 deletion.
• To understand the range of symptoms and diagnostic challenges.

Main Methods:

• Clinical examination of 21 patients from 10 families.
• Genetic testing, electrophysiological studies, and sural nerve biopsies.
• Telephone questionnaires to identify symptomatic individuals.

Main Results:

• Identified phenotypes include compressive neuropathy, symmetric peripheral neuropathy, acute brachial paralysis, and mononeuropathy multiplex.
• Many patients were oligosymptomatic, contributing to a majority of undiagnosed cases.
• HNPP can be misdiagnosed as Charcot-Marie-Tooth neuropathy.

Conclusions:

• The wide range of symptoms and mild presentations of HNPP contribute to underdiagnosis.
• Increased awareness of phenotypic variability is crucial for timely diagnosis.