41P Rigid spine syndrome revealing nemaline myopathy caused by a novel mutation in cofilin-2 gene (CFL2)

• Published in: Neuromuscular disorders : NMD Vol. 43; p. 104441
• Main Authors: Farhat, E., Miladi, N., Chaabouni, M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-10-2024
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2024.07.248

Rigid spine syndrome is a classically childhood-onset progressive and non-painful limitation of the neck and trunk flexion leading to postural abnormalities. Myopathies related to mutations in EMD, LMNA, SEPN1, COL6 and FHL1 genes are the most frequent causes. We report the case of a 10-year-old boy, born of consanguineous Libyan parents, who presents since the age of 7 years difficulties in the neck extension and progressive spine straightness. Motor and intellectual development were normal. On examination he showed a cachectic phenotype, spontaneous trunk flexion, prominent rigid spine, scapular winging, and flat retracted thorax. We found no spontaneous limb joint contractures. Weakness was more prominent in the cervicodorsal spine, and mild in the proximal upper limb muscles. Amyotrophy involved preferentially neck, trunk, and deltoid muscles. The patient is ambulant; however, his sport performance was limited and often complains about excessive fatigue. Creatine kinase levels were normal, and EMG showed myogenic pattern. On the deltoid muscle biopsy, we found the presence of numerous nemaline bodies confirming the diagnosis of nemaline myopathy (NM). The whole exome sequencing revealed the presence of a homozygous variant in the Cofilin-2 (CFL2) gene, a rare cause of autosomal recessive NM. The variant we found: NM_021914.7:c.115T>G p.(Cys39Gly), is classified as a variant of uncertain significance (class 3) according to the recommendations of ACMG. However, we considered it as a potentially relevant result, since the CFL2 gene is reported essentially in patients with NM, and the presence of multiple nemaline bodies on the patient's muscle biopsy.