ClinVar

Description

We report the case of a 7-month-old Moroccan male child presenting with congenital hypotonia, muscle weakness, dropped head syndrome, and normal heart function. In the literature, the NM_170707.4(LMNA):c.1718C>T (p.Ser573Leu) (dbSNP: rs60890628) variant in exon 11 of the LMNA gene has been identified in individuals across multiple forms: In the heterozygous state with dilated cardiomyopathy (Taylor 2003 PMID:12628721, Pasotti 2008 PMID:18926329, Dal Ferro 2017 PMID: 28416588, Burstein 2021 PMID: 32746448), hypertrophic cardiomyopathy (Francisco 2017 PMID: 28874324). Moreover, patients with Limb-Girdle or Emery-Dreifuss muscular dystrophy (Benedetti 2007 PMID: 17377071, Bernasconi 2018 PMID: 29693488), and familial partial lipodystrophy (Lanktree 2007 PMID: 17250669) were also reported. In the homozygous state, this variant has been reported in an individual with arthropathy, tendinous calcinosis, and progeroid features (Van Esch 2006 PMID: 16278265) with no cardiac involvement. The heterozygous missense c.1718C>T variant was not found in 138 Moroccan clinical exomes (in-house database), and It was classified as a pathogenic variant with PP5, PM1, PM2, PP2, PP3, and PS2 rules according to the recommendations of ACMG/AMP. We report for the first time a new phenotype associated with a de novo variant in exon 11 of the LMNA gene: Congenital muscular dystrophy. We assume that it is a strong candidate variation responsible for the phenotype in our patient.