[Familial cleft lip with or without coexisting cleft palate]

Area of Science:

• Medical Genetics
• Craniofacial Surgery
• Developmental Biology

Context:

• The etiology of clefts remains incompletely understood, with a suspected complex and heterogeneous origin.
• Clinical observations suggest a familial predisposition to clefts, despite the absence of identified causative genes.
• A significant cohort of 3180 children treated for cleft lip and/or palate between 1972-2001 provided data for this study.

Purpose:

• To investigate the etiological factors and inheritance patterns of cleft lip and palate (CLP) and isolated cleft palate (CP).
• To identify distinct genetic groups within cleft populations and assess recurrence risks.
• To explore correlations between cleft type, parental cleft status, and child's sex.

Summary:

• Analysis of 540 children with positive family histories revealed two distinct genetic groups: CLP and CP, each with different recurrence risks.
• A significant correlation was found between cleft type, child's sex, and the cleft status of affected parents.
• Specifically, male infants were more likely to inherit cleft lip or CLP from affected mothers/fathers, while isolated cleft palate showed a higher incidence in female infants.

Impact:

• This research contributes to a deeper understanding of cleft inheritance mechanisms.
• Findings may enable more precise predictions of cleft occurrence in future generations.
• The data holds potential for developing cleft prevention strategies and informing genetic counseling.