Congenital myotonic dystrophy associated with a chromosome pericentric inversion

Area of Science:

• Genetics
• Pediatrics
• Clinical Medicine

Background:

• Congenital myotonic dystrophy (CMyD) is a severe form of myotonic dystrophy with significant early-onset morbidity.
• The genetic underpinnings of CMyD are complex, with mutations in the DMPK gene being a primary cause, but other factors may contribute to its presentation.
• Chromosomal abnormalities have been infrequently associated with CMyD, necessitating further investigation into their role.

Observation:

• This report details two cases of CMyD in infants, each associated with a distinct pericentric chromosomal inversion.
• Case 1 involved a male infant with 46,XY,inv(9)(p11q13), inherited from an asymptomatic father, while the mother had clinical myotonic dystrophy (MyD) without chromosomal aberration.
• Case 2 involved a female infant with 46,XX,inv(4)(p15.31q25), whose mother had clinical MyD and the same inversion, while the father was unaffected.

Findings:

• The presence of pericentric inversions, specifically inv(9) and inv(4), in these CMyD cases suggests a potential link between these chromosomal rearrangements and the disease.
• The variable inheritance patterns observed (e.g., affected mother with normal chromosomes, affected child with affected parent carrying the inversion) highlight the complex genetic interactions in CMyD.
• These findings contribute to the understanding of the genetic heterogeneity and potential etiological factors involved in congenital myotonic dystrophy.

Implications:

• These cases suggest that pericentric inversions may represent a contributing factor or a specific subtype in the pathogenesis of congenital myotonic dystrophy.
• Further research into the mechanisms by which these inversions influence gene expression or function related to myotonic dystrophy is warranted.
• Identifying such chromosomal abnormalities could aid in genetic counseling and understanding the diverse clinical spectrum of CMyD.