From the Guidelines
Cleft palate is typically considered a multifactorial inheritance disorder, meaning it results from a combination of genetic and environmental factors. While there are some cases where cleft palate follows specific inheritance patterns (such as autosomal dominant, autosomal recessive, or X-linked), most cases do not follow a simple Mendelian inheritance pattern. Instead, multiple genes interact with environmental factors during fetal development to increase susceptibility. The genetic component involves variations in several genes, which play roles in facial development. Environmental factors that may contribute include maternal smoking, alcohol consumption, certain medications, and nutritional deficiencies during pregnancy, particularly insufficient folic acid.
Key Points
- The condition can appear sporadically in families with no history of cleft palate, yet families with one affected member have an increased risk of having another affected child compared to the general population.
- The recurrence risk for siblings of an affected child is approximately 2-5%, which is higher than the general population risk but lower than would be expected with simple Mendelian inheritance 1.
- Cleft palate is a complex condition that requires a comprehensive approach to management, including genetic counseling, speech and language assessment, and surgical treatment when necessary 1.
- Palatal abnormalities, including velopharyngeal dysfunction (VPD) and submucous cleft palate (SMCP), are common in children with 22q11.2 deletion syndrome, and require early assessment and treatment 1.
Management
- Patients with cleft palate should undergo a comprehensive evaluation, including genetic counseling, speech and language assessment, and palatal examination.
- Surgical treatment can lead to significant improvements in intelligibility and quality of life.
- Intensive speech-language therapy may be necessary throughout childhood, and early implementation of augmentative communication (eg, sign language) can promote language use and help avoid frustration.
From the Research
Types of Inheritance
- Cleft palate can be caused by different types of inheritance, including monogenic and multifactorial inheritance 2, 3.
- Monogenic inheritance refers to the inheritance of a single gene that causes the condition, while multifactorial inheritance involves the interaction of multiple genetic and environmental factors 2, 4.
- Some cases of cleft palate have been found to be associated with rare disease variants in genes such as TBX22, COL2A1, FBN1, PCGF2, and KMT2D 2.
- Other studies have suggested that cleft palate may be influenced by a combination of genetic and environmental factors, including the interaction of multiple genes and environmental factors 3, 4.
Specific Types of Inheritance
- Dominant inheritance of cleft of the soft palate has been reported in some families 5.
- X-chromosome linked cleft palate gene has been identified in a large Icelandic family 6.
- Oligogenic models with as few as four loci have been proposed to explain the inheritance of cleft lip with or without cleft palate 4.