Megaconial congenital muscular dystrophy secondary to novel CHKB mutations resemble atypical Rett syndrome.
J Hum Genet
; 66(8): 813-823, 2021 Aug.
Article
en En
| MEDLINE
| ID: mdl-33712684
ABSTRACT
Megaconial congenital muscular dystrophy (CMD)(OMIM #602541), related to CHKB mutation, is a rare autosomal recessive disorder. To date, only 35 confirmed patients are recorded. We present a detailed description of the clinical, histopathological, imaging, and genetic findings of five children from four Indian families. The children had moderate-to-severe autistic behavior, hand stereotypies, and global developmental delay mimicking atypical Rett syndrome. In addition, generalized hypotonia was a common initial finding. The progression of muscle weakness was variable, with two patients having a milder phenotype and three having a severe form. Interestingly, the majority did not attain sphincter control. Only patient 1 had classical ichthyotic skin changes. Muscle biopsy in two patients showed a myopathic pattern with characteristic peripherally placed enlarged mitochondria on modified Gomori trichrome stain and electron microscopy. Genetic analysis in these patients identified three novel null mutations in CHKB [c.1027dupA (p.Ser343LysfsTer86);c.224 + 1G > T (5' splice site); c.1123C > T (p.Gln375Ter)] and one reported missense mutation, c.581G > A (p.Arg194Gln), all in the homozygous state. Megaconial CMD, although rare, forms an important group with a complex phenotypic presentation and accounted for 5.5% of our genetically confirmed CMD patients. Atypical Rett syndrome-like presentation may be a clue towards CHKB-related disorder.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Síndrome de Rett
/
Colina Quinasa
/
Mitocondrias
/
Distrofias Musculares
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
J Hum Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
India