Mutations in <i>PTPN11</i> could lead to a congenital myasthenic syndrome phenotype: a Noonan syndrome case series

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article
Data de publicação
2024
DOI
Scopus
Web of Science
PubMed
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Editora
SPRINGER HEIDELBERG
Autores
PUGLIESE, Alessia
MARINA, Adela Della
ROOS, Andreas
SCHARA-SCHMIDT, Ulrike
HENTSCHEL, Andreas
AZUMA, Yoshiteru
TOPF, Ana
THOMPSON, Rachel
Citação
JOURNAL OF NEUROLOGY, v.271, n.3, p.1331-1341, 2024
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Unidades Organizacionais
Fascículo
Resumo
The RASopathies are a group of genetic rare diseases caused by mutations affecting genes involved in the RAS/MAPK (RAS-mitogen activated protein kinase) pathway. Among them, PTPN11 pathogenic variants are responsible for approximately 50% of Noonan syndrome (NS) cases and, albeit to a lesser extent, of Leopard syndrome (LPRD1), which present a few overlapping clinical features, such as facial dysmorphism, developmental delay, cardiac defects, and skeletal deformities. Motor impairment and decreased muscle strength have been recently reported. The etiology of the muscle involvement in these disorders is still not clear but probably multifactorial, considering the role of the RAS/MAPK pathway in skeletal muscle development and Acetylcholine Receptors (AChR) clustering at the neuromuscular junction (NMJ). We report, herein, four unrelated children carrying three different heterozygous mutations in the PTPN11 gene. Intriguingly, their phenotypic features first led to a clinical suspicion of congenital myasthenic syndrome (CMS), due to exercise-induced fatigability with a variable degree of muscle weakness, and serum proteomic profiling compatible with a NMJ defect. Moreover, muscle fatigue improved after treatment with CMS-specific medication. Although the link between PTPN11 gene and neuromuscular transmission is unconfirmed, an increasing number of patients with RASopathies are affected by muscle weakness and fatigability. Hence, NS or LPDR1 should be considered in children with suspected CMS but negative genetic workup for known CMS genes or additional symptoms indicative of NS, such as facial dysmorphism or intellectual disability.
Palavras-chave
RASopathies, Noonan syndrome, Leopard syndrome, PTPN11, Congenital myasthenic syndrome, Neuromuscular junction
URI
https://observatorio.fm.usp.br/handle/OPI/58924
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MNE