Dados do Trabalho

Título

CONGENITAL MYASTHENIC SYNDROME DUE TO A MUTATION IN THE RAPSN GENE

Apresentação dos casos

Male patient, the result of an unplanned and unattended pregnancy. He
was born at full term, by vaginal delivery. He described a laborious delivery and
developed an epileptic seizure in the first few hours of life. During hospitalization, he
had several neonatal complications, including respiratory failure, requiring mechanical
ventilation. Neurological examination revealed global hypotonia, a myopathic face,
associated with proximal weakness and reduced reflexes, with cognitive impairment
expected for his age. He developed significant swallowing disorders, requiring
gastrostomy and tracheostomy. An investigation for congenital infection was carried out
and ruled out. MRI of the skull showed widening of the cerebrospinal fluid space in the
bilateral frontotemporal region with slight accentuation of the Sylvian fissures. Since the
neuroimaging findings did not justify the neurological condition and the clinical picture
was suggestive of neuromuscular disease, he underwent genetic investigation, with a
46XY karyotype, and molecular testing was carried out with the identification of a
probably pathogenic variant in RAPSN - chr11:47.469.402; NM_005055.5:c.493 G>A:p.
(Val165Met) and a pathogenic variant in RAPSN - chr11:47.469.631;
NM_005055.5;C.264C>A:p. (Asn88Lys). A diagnosis of congenital myasthenic
syndrome was made. Pyridostigmine was started, with improvement in the neurological
condition, acquiring some motor milestones, such as cephalic support, trunk support
with support, improvement in limb strength.

Discussão

MCS encompasses a group of genetic diseases with a heterogeneous
phenotype, resulting in defects in genes that code for neuromuscular junction proteins.
The severity and course of the disease are highly variable. In this case, the patient had
early onset symptoms, with a myopathic face, global hypotonia, delayed
neuropsychomotor development and significant bulbar symptoms not justified by other
causes. A genetic test for neuromuscular disease was carried out, with a diagnosis of
MCS due to a mutation in the RAPSN gene.

Comentários finais

We report a case of SMC with a mutation in the RAPSN gene, with a
clinical picture of hypotonia since the neonatal period, associated with bulbar
symptoms. Early diagnosis of this form of presentation is vitally important, as patients
have an excellent response to treatment with pyridostigmine and a good long-term
prognosis.

Referências

Engel AG, Shen XM, Selcen D, Sine SM. Congenital myasthenic syndromes:
pathogenesis, diagnosis, and treatment. Lancet Neurol. 2015 Apr;14(4):420-34. doi:
10.1016/S1474-4422(14)70201-7. Erratum in: Lancet Neurol. 2015 May;14(5):461. doi:
10.1016/S1474-4422(15)00010-1. PMID: 25792100; PMCID: PMC4520251.
Finsterer J. Congenital myasthenic syndromes. Orphanet J Rare Dis. 2019 Feb
26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424; PMCID:
PMC6390566.

Abicht A, Müller JS, Lochmüller H. Congenital Myasthenic Syndromes Overview. 2003
May 9 [updated 2021 Dec 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA,
Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews ®  [Internet].
Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301347.

Palavras Chave

congenital myasthenic syndrome; hypotonic baby syndrome; RAPSN gene mutation