Objective: To make the first case report of SPSMA associated with TRPV4 gene mutation in the Peruvian population presented in a young Peruvian woman.

Background: The TRPV4 gene encodes a mechanosensitive ion channel involved in calcium homeostasis and cellular signal transduction. This gene is associated with hereditary neuropathies and skeletal dysplasias. A heterozygous mutation of this gene causes SPSMA. This rare disease is mainly characterized by slowly progressive weakness that affects the shoulder girdle, peroneal muscles, and facial weakness without sensory loss. It is also associated with neurogenic scapuloperoneal amyotrophy, laryngeal palsy, congenital muscle absence, and skeletal abnormalities.

Method: A 17-year-old female presented an 8-year history of progressive muscle weakness, gait instability, muscle cramps, chronic pain, retro lateral pulsion, vertigo-like sensations, and difficulty descending stairs, which was particularly challenging due to a condition that we refer to as the “Stairs Conundrum,” where her difficulty in descending stairs compounded a combination of muscle weakness and balance issues, the patient required to adopt a broader stance to maintain balance. She has antecedents of bilateral congenital hip dysplasia and pincer-type femoroacetabular impingement, for which she underwent bilateral knee surgeries on two occasions. Clinical examination revealed pale, tense skin, a slightly atrophic geographic tongue, uvula deviation to the left, and a hypophonic voice. The neurological assessment showed hypotonia, muscle weakness (3/5), bilateral Hoffman’s, Marinescu’s reflexes, positive Romberg’s sign, and cogwheel rigidity in the left hemibody.

Results: Laboratory findings indicated high CPK levels and positive anti-Jo antibodies. Whole exome sequencing demonstrated an incidental mutation in the TRPV4 gene, characterized by a heterozygous single-nucleotide variant (G>C), resulting in an amino acid substitution. She was treated with IV methylprednisolone (1 gram per day for 5 days), which led to symptom improvement.

Conclusion: The present abstract demonstrates that in the presence of neuropathic pain, weakness, and myopathy of unknown cause, a channelopathy such as TRPV4 mutation could underlie the existence of a disease such as CMT C2, SPSMA or congenital distal spinal muscular atrophy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-young-peruvian-woman-with-a-stairs-conundrum-scapuloperoneal-spinal-muscular-atrophy-spsma-due-to-a-trpv4-mutation-case-report/