Charcot-Marie-Toothe Disease presenting with tremor; a rare presentation of hereditary polyneuropathy

Abstract

Abstract Background: Charcot-Marie-Toothe (CMT) disease is a spectrum of inherited disorders caused by abnormalities in genes that are expressed in peripheral nerve myelin and/or axons. Typical features include both motor and sensory nerve manifestations with distal leg weakness, foot deformities (pes cavus, hammer toes), and sensory deficits. Postural tremor as a manifestation of CMT is seldom present, except in a variant of CMT1 (Roussy-Levy Syndrome), whose presentation includes postural tremor, gait ataxia, distal muscle atrophy, pes cavus, areflexia, and mild distal sensory loss. Case Presentation: We present a 34-year-old right-handed male patient with tremor of the hands of 6 months duration. Associated with this, he has difficulty walking and weakness of the distal extremities bilaterally, initially and prominently involving the lower limbs. The patient says that his way of walking has been different as long as he remembers (slapping against the ground whenever he walks). The patient has no history of diabetes, hypertension, or any other chronic illness, and he has no family history of such illness. Physical examination revealed mild distal muscle weakness (4+/5 on upper limbs, while 3/5 on lower limbs), pes cavus deformity, absent ankle reflexes and mild vibratory sensory loss. We noted a postural tremor, that attenuates when the patient assumes anatomic position. The tremor is limited to the hands. NCS of Upper and lower Limbs showed moderate to severe motor axonal and demyelinating Polyneuropathy (Axonal > Demyelinating)- Suggestive of axonal predominant hereditary polyneuropathy. Subsequently done genetic testing revealed copy number changes (Heterozygous Deletion) on the MPZ and MFN2 Genes could be associated with CMT1B and CMT2A respectively; while the PMP22 gene showed ambiguous copy number changes (decrease) on exons 2 and 3. Tying the clinical, electrophysiologic and genetic findings, a consideration of CMT2A with postural tremor was made. Conclusion: The present case describes a 34-year-old male patient with CMT2A presenting with neuropathic postural tremor, which is a rare presentation of a common hereditary polyneuropathy. This case highlights the fact that tremors can be associated with peripheral neuropathy syndromes, and a high index of suspicion is needed to rightly diagnose our patients.