What is a case study of hereditary neuropathy with predisposition to pressure palsy (HNPP) in Charcot-Marie-Tooth (CMT) disease?

Updated: Feb 19, 2019
  • Author: Francisco de Assis Aquino Gondim, MD, PhD, MSc, FAAN; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

Answer

A clinical vignette is as follows:

A 42-year-old man was referred for evaluation of diffuse body aches. He had a history of episodic bilateral wrist drop; intermittent limb numbness, often after repetitive movements; and muscle cramps since age 20 years. On examination, he had subtle abnormalities. Panmodal sensory loss was found in a right ulnar and peroneal and left median and ulnar distribution. Power, bulk, gait, and coordination were intact, but distal hyporeflexia was present. Tinel signs were present at the wrists and elbows. No nerves could be palpated. Hammertoes and high arches were present.

Findings on routine laboratory studies, such as erythrocyte sedimentation rate, vitamin B-12, folate, rapid plasma reagin, antinuclear antibodies, rheumatoid factor, thyroid function, HgA1c, creatine kinase, and HIV antibodies, were noncontributory, but hepatitis C serology was positive. His 65-year-old mother provided a history of finger numbness and postpartum arm weakness, and she had distal hyporeflexia and decreased sensation. His 81-year-old great-aunt was similarly affected.

His daughter, aged 18 years, had numbness and tingling in the back of her legs during gym class and middle finger numbness when holding a pen or playing the flute, but she denied episodic weakness; symptom onset was at age 13 years. She had high arches and hammertoes, slightly weak finger extension, mild distal pansensory impairment, and a Romberg sign. Her 15-year-old sister was reluctant to attend gym class because of foot numbness; symptoms improved when she shook her legs. Either hand occasionally went numb, especially the right thumb when writing. Once after sitting on her cousin's shoulders, both legs were weak for 20 minutes. Her examination findings were remarkable only for weak interossei in both hands. Two younger children were asymptomatic but had distal pinprick and vibratory sense loss with normal proprioception, strength, and reflexes.

Electrodiagnostic studies in 1987, 1988, and 1996 in the father revealed multiple nerve entrapments at both median and ulnar nerves at the wrists, the ulnar nerves at the elbows, the right radial nerve at the spiral groove, and the right peroneal nerve at the fibular head. Conduction velocities were normal or low-normal except for slowing in the demyelinative range at areas of nerve entrapment, where amplitudes were also low. No significant change occurred over time in nerves studied repeatedly.

Light and electron microscopy of the father's sural nerve biopsy specimen showed prominent sausage-shaped expansion of the myelin sheath in the perinodal and internodal regions, the classic finding that gives this condition its other name—tomaculous neuropathy; thinly myelinated fibers; and reduction in large myelinated fiber density with a shift of fiber diameters to small sizes. Areas of incomplete myelin compaction and redundant loops of the myelin sheath were present. Genetic testing revealed a deletion of the 1.5-Mb gene region that harbors the PMP22 gene in all affected family members as well as in the 2 asymptomatic younger daughters.

This family illustrates the typical presentation of PMP22 deletions, but the diagnosis is not always as straightforward.


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