Hereditary Neuropathy With Liability to Pressure Palsies

253 Hereditary neuropathy with liability to pressure palsy is a rare autosomal dominant disorder characterized by multiple episodes of focal demyelinating neuropathies after minor trauma to peripheral nerves. It usually appears in early adulthood with recurrent attacks of pain, numbness, and muscular weakness along the distribution of the clinically affected nerve. Segmental demyelination and thickenings of the myelin sheath are the pathologic findings. Electrophysiologic studies show a nonuniform mild demyelinating neuropathy with prolonged distal latencies. Genetic tests are available to aid in diagnosis as molecular analysis has identified a deletion in the chromosome 17p11.2 in the majority of these patients. There is a paucity of information in the orthopaedic literature regarding hereditary neuropathy with liability to pressure palsy. A case report is presented of a patient with this disorder to promote awareness and recognition that this entity should be considered in patients with multiple nerve palsies. Hereditary neuropathy with liability to pressure palsies is characterized by periodic motor and sensory findings and often by nerve palsies after minor compression injuries or trauma of a peripheral nerve. Hereditary neuropathy with liability to pressure palsies manifests as an autosomal dominant multifocal neuropathy usually appearing during adolescence, with recurrent attacks of numbness, muscular weakness, and paresthesias that usually improve and recover within a few months. Segmental demyelination and thickenings of the myelin sheath (tomaculous or sausage-like structures) are typical histopathologic findings in hereditary neuropathy with liability to pressure palsy.1 Most patients have deletion of chromosome 17p11.2 and a genetic test is available for this condition.4 Although this entity is described in the genetic and neurologic literature, the case presented here is the first to the authors’ knowledge to be reported in the orthopaedic literature.

Hereditary neuropathy with liability to pressure palsy is a rare autosomal dominant disorder characterized by multiple episodes of focal demyelinating neuropathies after minor trauma to peripheral nerves. It usually appears in early adulthood with recurrent attacks of pain, numbness, and muscular weakness along the distribution of the clinically affected nerve. Segmental demyelination and thickenings of the myelin sheath are the pathologic findings. Electrophysiologic studies show a nonuniform mild demyelinating neuropathy with prolonged distal latencies. Genetic tests are available to aid in diagnosis as molecular analysis has identified a deletion in the chromosome 17p11.2 in the majority of these patients. There is a paucity of information in the orthopaedic literature regarding hereditary neuropathy with liability to pressure palsy. A case report is presented of a patient with this disorder to promote awareness and recognition that this entity should be considered in patients with multiple nerve palsies.
Hereditary neuropathy with liability to pressure palsies is characterized by periodic motor and sensory findings and often by nerve palsies after minor compression injuries or trauma of a peripheral nerve. Hereditary neuropathy with liability to pressure palsies manifests as an autosomal dominant multifocal neuropathy usually appearing during adolescence, with recurrent attacks of numbness, muscular weakness, and paresthesias that usually improve and recover within a few months. Segmental demyelination and thickenings of the myelin sheath (tomaculous or sausage-like structures) are typical histopathologic findings in hereditary neuropathy with liability to pressure palsy. 1 Most patients have deletion of chromosome 17p11.2 and a genetic test is available for this condition. 4 Although this entity is described in the genetic and neurologic literature, the case presented here is the first to the authors' knowledge to be reported in the orthopaedic literature.

CASE REPORT
A 41-year-old right-hand dominant woman presented with a 1-week history of inability to extend her wrist and fingers on the right side. She gave a history of catching a falling patient in the course of her work as a physical therapist. This involved forceful muscle contraction of her upper extremities, but no direct trauma or external compression.
The patient had a history of two previous nerve palsies. Three years before this incident the patient felt pain in the right shoulder the day after a vigorous game of tennis. Scapular winging was present. A diagnosis of long thoracic nerve palsy was made. This resolved after 9 months of careful observation. One year before that episode, the patient felt leftsided neck pain 1 day after abdominal surgery. Lack of trapezius function was seen and the diagnosis of spinal accessory nerve palsy was made. This was confirmed by electrodiagnostic studies and resolved after 4 months of observation. The patient is unaware of any nerve palsies in blood relatives. Her father died of amyotrophic lateral sclerosis.
Physical examination of the right upper extremity revealed 5 ⁄ 5 triceps and brachioradialis, 3 ⁄ 5 extensor carpi radialis longus, and 0 ⁄ 5 extensor carpi radialis brevis, extensor digitorum communis, extensor carpi ulnaris, extensor pollicis longus, extensor pollicis brevis, and abductor pollicis longus. There was decreased sensation over the radial nerve distribution of the hand. Pulses were normal. Tinel's sign was present over the spiral groove of the humerus. The patient's electromyographic study was severely abnormal and consistent with posterior interosseus neuropathy. Testing for the chromosome 17p11.2 deletion was negative. Physical examination at 4 months continued to show a positive Tinel's sign, motor strength similar to initial presentation, and improvement in sensation to light touch.
The patient was treated with nonsteroidal antiinflammatory drugs and a low profile extension outrigger splint at the initial presentation. Her symptoms began to subside by 6 months and resolved by 8 months with full return of radial motor and sensory nerve function. Repeat electrodiagnostic studies were not done as the patient was asymptomatic and refused.

DISCUSSION
Hereditary neuropathy with liability to pressure palsies is well described in the genetic and neurologic literature. 2,5,6,9 It is less well-known to hand surgeons. An extensive literature search did not reveal any references to this diagnosis in the hand or orthopaedic literature. Hereditary neuropathy with liability to pressure palsies is an autosomal dominant disorder. Affected patients sustain nerve palsies after seemingly minimal trauma including pregnancy and delivery. These palsies generally re-solve without surgical intervention. Typically, patients experience multiple palsies with time. This usually manifests in adolescence and 20to 30-year old patients, although it has been reported in patients as young as 4 years of age. 1,9 Electrophysiologic tests show that the nerve conduction velocities may be locally slowed in or near anatomic pressure points. The hallmark is nonuniform mild demyelinating neuropathy with prolonged distal latency, which is out of proportion to nerve conduction velocity slowing. 8 The classic pattern is the presence of focal nerve lesions in the clinically affected nerves superimposed on a generalized neuropathy affecting motor and sensory fibers in clinically unaffected nerves. 8 Tyson et al 9 also showed that nerve conduction studies were either normal outside clinically affected territories, or showed evidence of patchy or generalized axonal neuropathy. 9 Nerve biopsy shows segmental demyelination, remyelination, focal thickenings of the myelin sheath termed tomacula, and a variable degree of axonal loss. 10 Genetic testing for the deletion of chromosome 17p11.2 involves Southern blotting and fluorescent in situ hybridization analysis. 5 The deletion of chromosome 17p11.2 in hereditary neuropathy with liability to pressure palsies appears to be the reciprocal meiosis product of the 17p11.2 duplication seen in Charcot-Marie-Tooth disease Type 1. 2,4,6,9 Charcot-Marie-Tooth disease, the most common peripheral neuropathy, also shows slow nerve conduction velocities with prolonged distal latencies in patients with Type 1 disease but the electrophysiologic examination shows a uniform demyelination neuropathy and the clinical picture also is distinctly different. Patients present in the first or second decade of life with foot drop and slowly progressive distal muscle atrophy and foot deformities including pes cavus and hammertoes. 1 Intrinsic muscle wasting in the hands begins later and patients may acquire a stocking-glove decrease in vibration, pain, temperature sensation, and absent deep tendon reflexes. These patients have been classified by genetic loci according to deoxyribonucleic acid (DNA) link-Clinical Orthopaedics age studies into A, B, and C. 1 Patients who carry a duplication of chromosome 17p11.2 have been shown to have Charcot-Marie-Tooth peripheral neuropathy Type 1A and, conversely, patients with deletions of the same region have been shown to have hereditary neuropathy with liability to pressure palsies. 3 A European collaborative study found that 84% of patients with hereditary neuropathy with liability to pressure palsies tested positive for this chromosomal deletion, 6 and 71% of patients with Charcot-Marie-Tooth disease Type 1 had the 17p11.2 duplication. 6 The chromosome 17p11.2 locus includes a peripheral myelin protein 22 gene that seems to determine the phenotypic consequences mentioned above. 3 Several patients with Charcot-Marie-Tooth disease Type 1 have tested negative for duplication of chromosome 17p11.2, but have had a point mutation in the peripheral myelin protein 22 gene on DNA testing. 1 Similarly, Nicholson et al 7 reported on a patient with hereditary neuropathy with liability to pressure palsy who did not possess the chromosome 17p11.2 deletion but did have a point mutation of the peripheral myelin protein 22 gene, which effectively caused a functional deletion of the gene. Therefore, patients who appear clinically to have hereditary neuropathy with liability to pressure palsies but are negative for the 17p11.2 deletion may have a point mutation in the peripheral myelin protein 22 which causes the same effect as the larger deletion and this may have been the case in the patient presented above.
Awareness by hand and upper extremity surgeons of hereditary neuropathy with liability to pressure palsies is important. The diagnosis of this entity should be considered in patients with multiple nerve palsies, either occurring together or separately, and in patients with a single nerve palsy and a positive family history for multiple nerve palsies. This awareness will lessen the chance of nonproductive surgery, heighten precautions to protect peripheral nerves in patients at risk, and enhance patient education through genetic counseling.