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Título

MORC2 related neuropathy associated with autonomic dysfunction

RESUMO

Case report: A 27-year-old female, borned from non-consanguineous and healthy parents. She presented in her first decade of life with distal and proximal asymmetrical weakness, sensory loss, generalized arreflexia. She also presented cognitive impairment. Nerve conduction studies revealed sensory and motor axonal neuropathy. WES revealed a class 5 variant in the MORC2 gene (NM_001303257.2:c.754C>T ; p.Arg252Trp) confirming the diagnosis of CMT2Z. Sanger sequencing of her parents confirmed it was a de novo variant. At 26 years old, she reported episodes of recurrent abdominal pain, early satiation, bloating, nausea, vomiting, constipation and progressive weight loss. Blood pressure standing and lying, as well as heart rate due valsalva maneuver were normal. Gastric emptying scintigraphy showed that gastric emptying time T1/2 was greater than 30 minutes, with gastric retention of about 70% of the content at the end of the study, confirming gastrointenstinal specific autonomic dysfunction.

Discussion: Charcot-Marie-Tooth disease type 2Z is a rare form of autosomal dominant axonal neuropathy. Clinical findings include sensory impairment, distal and proximal weakness, distal atrophy and muscle cramps. Also, there are reports of global hypotonia, including MORC2-related disorder in the differential of non-51 SMA. Additionally, intellectual disability, hearing loss, microcephaly, pyramidal signs and brain atrophy have been reported. MORC2 protein regulates DNA transcription and is important for cytoplasmatic function. In a literature review, dysautonomia is not reported in patients with CMT2Z, but it is well established the secondary involvement of MORC2 in mitochondrial function and maintenance. Additionally, there is a Leigh-Like case previously reported sin association to MORC2.

Final comments: We report a case of CMT2Z caused by a de novo MORC2 gene mutation in a patient presenting with gastrointestinal isolated dysautonomia. We hypothesized that this mutation may affect mitochondiral machinery. Further data studies are necessary to elucidate the relationship between mutation in MORC2 gene and dysautonomia.

Palavras Chave

Charcot-Marie-Tooth disease ; axonal CMT; autonomic dysfunction; hereditary neuropathy