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Título

A CASE REPORT OF A DE NOVO MUTATION IN TPM3 GENE CAUSING DOMINANT CONGENITAL MUSCULAR DYSTROPHY 4A (CMYP4A)

Apresentação do caso único

3y9m (F) began investigation due to delayed neuropsychomotor development, in which she sat at 11 months and walked without support at 1 year and 9 months, followed by developmental regression at 2 years old, when she stopped walking. Associated with this, she also had recurrent pneumonias. Hypothesis of a neuromuscular disease was raised, a broad DNA panel was collected, which showed a probably pathogenic variant in TPM3 - heterozygosity chr1:154192012 C>G, p.Glu3Gln. Electroneuromyography was performed with myopathic pattern, without metabolic or echocardiographic laboratory changes. Currently, without sphincter control due to difficulty positioning in a seat. On clinical examination, myopathic, elongated facies, half-open mouth, global hypotonia with global strength 3+, inability to walk, global hyporeflexia and dysarthria. She's currently receiving treatment with inhaled corticosteroids for her pulmonary condition, together with motor adaptation, physiotherapy, use of an orthosis and multidisciplinary monitoring.

Discussão

CMYP4A, an autosomal dominant disease, caused by a heterozygous mutation in the TPM3 gene on chromosome 1q21. The TPM3 gene is an indispensable regulator of muscle contraction in slow muscle fibers, and its mutations have been associated with the characteristics of congenital myopathies. This change begins with symptoms in childhood. The severity of the clinical picture is variable, with the majority of those affected presenting motor delay, hypotonia, generalized muscle weakness, with normal cognitive development, in addition to respiratory impairment, with a possible need for non-invasive ventilation. Other characteristics such as deformities of the spine and chest (scoliosis, lumbar lordosis), myopathic facies (high arched palate, long and narrow face), facial weakness (hypomimia and ptosis), drop feet, hyporeflexia, reduced muscle mass are commonly observed in these patients. On the other hand, the extraocular and cardiac muscles are often spared in patients with the mutation in question. Myopathy related to TPM3 has been described since 1992, with some patients already in adulthood, but all reporting the onset of motor symptoms since early childhood, respiratory involvement and musculoskeletal changes.

Comentários finais

Until 2014, only 3 de novo mutations had been reported. Furthermore, there is an urgent need to improve the diagnosis of TPM3-related myopathy as well as understand the molecular causes of the disease, however it remains uncurable.

Referências

1. LAMBERT, Matthias R.; GUSSONI, Emanuela. Tropomyosin 3 (TPM3) function in skeletal muscle and in myopathy. Skeletal Muscle, [S.L.], v. 13, n. 1, p. 1-18, 7 nov. 2023. Springer Science and Business Media LLC. http://dx.doi.org/10.1186/s13395-023-00327-x.

2. WADDELL, Leigh B; KREISSL, Michaela; KORNBERG, Andrew; KENNEDY, Paul; MCLEAN, Catriona; LABARRE-VILA, Annick; MONNIER, Nicole; NORTH, Kathryn N; CLARKE, Nigel F. Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3. Neuromuscular Disorders, [S.L.], v. 20, n. 7, p. 464-466, jul. 2010. Elsevier BV. http://dx.doi.org/10.1016/j.nmd.2010.05.012.

Palavras Chave

Neuromuscular Disease; Congenital Muscular Dystrophy; Tropomyosin-3