Inherited focal, episodic neuropathies: HNPP and HNA

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Neuromolecular Med. 2006;8(1-2):159-74.

Inherited focal, episodic neuropathies: hereditary neuropathy with

liability to pressure palsies and hereditary neuralgic amyotrophy.

Chance PF.

Division of Genetics and Developmental Medicine, Children's Hospital

and Regional Medical Center, Departments of Pediatrics and Neurology,

University of Washington School of Medicine, Box 356320, Room RR247,

Seattle, Washington 98195.

Hereditary neuropathy with liability to pressure palsies (HNPP; also

called tomaculous neuropathy) is an autosomal-dominant disorder that

produces a painless episodic, recurrent, focal demyelinating

neuropathy. HNPP generally develops during adolescence, and may cause

attacks of numbness, muscular weakness, and atrophy. Peroneal

palsies, carpal tunnel syndrome, and other entrapment neuropathies

may be frequent manifestations of HNPP.

Motor and sensory nerve conduction velocities may be reduced in

clinically affected patients, as well as in asymptomatic gene

carriers. The histopathological changes observed in peripheral nerves

of HNPP patients include segmental demyelination and tomaculous

or " sausage-like " formations.

Mild overlap of clinical features with Charcot-Marie-Tooth (CMT)

disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed

as having CMT1. HNPP and CMT1 are both demyelinating neuropathies,

however, their clinical, pathological, and electrophysiological

features are quite distinct.

HNPP is most frequently associated with a 1.4-Mb pair deletion on

chromosome 17p12. A duplication of the identical region leads to

CMT1A.

Both HNPP and CMT1A result from a dosage effect of the PMP22 gene,

which is contained within the deleted/duplicated region. This is

reflected in reduced mRNA and protein levels in sural nerve biopsy

samples from HNPP patients.

Treatment for HNPP consists of preventative and symptom-easing

measures. Hereditary neuralgic amyotrophy (HNA; also called familial

brachial plexus neuropathy) is an autosomal-dominant disorder causing

episodes of paralysis and muscle weakness initiated by severe pain.

Individuals with HNA may suffer repeated episodes of intense pain,

paralysis, and sensory disturbances in an affected limb. The onset of

HNA is at birth or later in childhood with prognosis for recovery

usually favorable; however, persons with HNA may have permanent

residual neurological dysfunction following attack(s).

Episodes are often triggered by infections, immunizations, the

puerperium, and stress. Electrophysiological studies show normal or

mildly prolonged motor nerve conduction velocities distal to the

affected brachial plexus. Pathological studies have found axonal

degeneration in nerves examined distal to the plexus abnormality. In

some HNA pedigrees there are characteristic facial features,

including hypotelorism.

The prognosis for recovery of normal function of affected limbs in

HNA is good, although recurrent episodes may cause residual deficits.

HNA is genetically linked to chromosome 17q25, where mutations in the

septin-9 (SEPT9) gene have been found.