Associations Between Alcohol Dehydrogenase Mutations and Cleft Lip/Palate: A Scoping Review.

Area of Science:

• Genetics
• Developmental Biology
• Pharmacogenomics

Background:

• Cleft lip with or without cleft palate (CL±P) incidence varies by genetic ancestry.
• Alcohol dehydrogenase (ADH) gene family polymorphisms differ significantly across populations.
• Limited studies suggest a link between ADH variants and CL±P risk.

Purpose of the Study:

• To conduct a scoping review on the association between ADH gene polymorphisms and CL±P risk.
• To synthesize existing evidence on ADH variants and their potential role in CL±P etiology.
• To identify gaps in current research regarding ADH, ancestry, and CL±P.

Main Methods:

• Systematic literature search of PubMed and Medline databases.
• PRISMA 2020 guidelines followed for study selection.
• Inclusion of case-control, cohort, case-series, and cross-sectional studies (1966-2024) reporting ADH polymorphisms and CL±P associations.

Main Results:

• Five studies (1630 CL±P cases) met inclusion criteria.
• Four studies linked maternal/fetal ADH1C polymorphisms to CL±P risk.
• One study found ADH1C genotype modified prenatal alcohol exposure risk for CL±P; another found no effect. A novel ADH7 duplication was also reported.

Conclusions:

• Limited evidence suggests maternal and fetal ADH polymorphisms may influence CL±P risk.
• Current data predominantly from homogenous cohorts; ancestry analysis with ADH polymorphisms is lacking.
• The interplay of genetic ancestry, ADH mutations, and CL±P remains an open research question.