Unraveling the Overlapping Spectrum of Hereditary Neuropathies: Clinical and Genetic Insights From the UAE

TL;DR

This study explores the clinical and genetic diversity of hereditary neuropathies in the UAE, emphasizing the need for comprehensive diagnostic approaches.

Contribution

The paper provides new clinical and genetic insights into HSMNs in the UAE population through detailed case studies.

Findings

Patients exhibited a range of symptoms from episodic focal neuropathies to progressive motor impairment.

Genetic testing identified mutations including PMP22 duplications, deletions, GJB1, and SH3TC2.

Phenotypic overlap between HNPP and CMT was observed, highlighting diagnostic challenges.

Abstract

Hereditary sensory and motor neuropathies (HSMNs) remain underreported in the United Arab Emirates (UAE), where overlapping clinical features often delay diagnosis. These case series describe the clinical and genetic diversity of HSMNs through the evaluation of five Emirati male patients, aged 18-47 years diagnosed with Charcot-Marie-Tooth disease (CMT) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP), focusing on phenotypic variability and diagnostic challenges. Patients presented with a range of symptoms, from episodic focal neuropathies to progressive distal weakness and motor impairment. Clinical assessment, electrophysiological studies and genetic testing revealed a number of underlying mutations, including PMP22 duplications (CMT1A), PMP22 deletions (HNPP), GJB1 mutation (CMTX), and SH3TC2 mutation (CMT4C). The CMT4C case exhibited early-onset scoliosis and severe neuropathy, while others exhibited milder or episodic symptoms. One HNPP patient with a PMP22 deletion exhibited progressive deficits resembling CMT, emphasizing the phenotypic overlap between HNPP and CMT. Electrophysiological studies showed demyelinating polyneuropathy with varying degrees of axonal involvement. These findings highlight the challenges posed by HSMNs and the importance of integrating clinical assessment, electrophysiological evaluation, and comprehensive genetic testing for accurate diagnosis and management. This multidisciplinary approach is critical for distinguishing between CMT and HNPP, offering clarity in cases with atypical or overlapping phenotypes and supporting the need for personalized care.

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