Hereditary Neuropathy with Liability to Pressure Palsies: A Clinical And Molecular Study in a South African Family of Indian Descent

Background Hereditary neuropathy with liability to pressure palsy (HNPP) first described in 1947, has been showed to be due to a 1.5Mb deletion, which includes the peripheral myelin protein 22 (PMP22) gene, on chromosome 17p11.2. HNPP is more common than previously thought. Objective We describe the clinical and molecular features in a three generation family where the index case became acutely disabled following surgery for cervical spondylosis. Method A total of 14 (including the index case) were examined. Eleven had clinical evidence of disease. The disability of this group ranged from asymptomatic (1), mild (4), moderate (4), severe (1) to death (1). The findings on examination ranged from a single nerve involvement to a confluent mononeuropathy multiplex. The patient who died had marked proximal and distal weakness. The immediate cause of death is unknown. On history two individuals (now deceased) were said to be affected. A further 2 subjects who were not available for examination but who provided blood for molecular analysis were said to be normal. A PCR based strategy for the determination of the PMP22 gene dose was undertaken in 15 subjects. Results Four of these individuals (2 on history and 2 on examination) who were clinically normal had no deletions. All the clinically affected individuals all exhibited the appropriate deletion. One was clinically normal but carried the deletion. Sample from a 16th individual, who was not examined, was insufficient. Conclusion This study is the first report of the existence of HNPP in South Africa. Cases are probably being missed. The correct diagnosis is important, as with appropriate measures and patient education, disability can be significantly reduced. Resume Introduction Decrite en 1947, la neuropathie hereditaire avec hypersensibilite a la pression (NHHP) est une neuropathie hereditaire sensitivomotrice a transmission autosomique dominante. Cette affection est liee a un defaut de synthese d\'une proteine de la myeline : la proteine PMP22 (peripheral myelin protein 22) en rapport dans pres de 90% des cas a une deletion de 1,5 megabases dans la region 17p11.2 incluant le gene PMP22. L\'HNPP parait plus frequent qu\'on ne le pensait. Objectif Nous decrivons les aspects cliniques et moleculaires d\'une famille sud africaine d\'origine indienne, sur trois generations, decouverte lors d\'une decompensation aigue suite a une intervention pour une myelopathie cervicarthrosique. Materiel et methodes 14 cas ont ete etudies. 11 patients avaient des signes cliniques evidents. Le groupe a ete classe selon les aspects suivants : asymptomatique, discret, modere, severe et deces. Les constatations etaient en rapport avec une atteinte tronculaire nerveuse, unique ou multiple. . Une enquete familiale a permis de realiser des examens cliniques et biologiques . Resultats Le PCR a ete pratique chez 15 patients. Quatre des patients asymptomatiques n\'avaient pas de deletion. Tous les patients symptomatiques avaient une deletion. Un patient asymptomatique etait porteur d\'une deletion.. Le patient decede de cause inconnue presentait une faiblesse proximale et distale tres marquee Conclusion Il s\'agit du premier cas rapporte en Republique Sud-Africaine sans que cela ne prejuge du nombre de cas qui est vraisemblablement sous-estime. Le diagnostic de HPPN ne doit pas etre omis compte tenu des eventuelles consequences fonctionnelles. (Af. J. of Neurological Sciences: 2003 22(1))