Genetic analysis of syndromic and non-syndromic

cleft lip and cleft palate

 Cleft lip and palate (CL/P) is one of the most prevalent congenital anomaly associated
with caraniofacial region. It is characterised by the lack of integrity in the alveolar bone,
lip muscles and hard and soft palate.

 Globally, it affects about 1 in 700 live births; but, among Asian and American
communities, the frequency may reach 1 in 500.

 Majority (70%) of CL/P are non syndromic in nature (NSCLP), whereas 30% of CL/P
cases manifest as syndromic ones (SCLP) (Stainer et al., 2004).

 Genetically CL/P acts as monogenic as well as chromosomal syndrome and is inherited

as autosomal recessive, autosomal dominant and X linked disorder (Kalay et al., 2012).

 Multiple genes (MSX1, TBX22, IRF6, TGFA, TGFb3) and chromosomal abnormalities
(22q11.2 deletion, 8q22.1-8q24.3 del, 5p15.33 dup, 17p13.3 dup) have been reported in
SCLP and NSCLP.
 Objectives

 Collection of blood samples, pedigree and clinical history of affected individuals.

 Screening of suspected subjects for chromosomal abberations by Karyotyping.

 Genetic analysis of individuals for frequent syndromic [Van der Woude syndrome, Velocardiofacial

syndrome VCF, popliteal pterygium syndromes] and non syndromic cleft lip with or without cleft

palate by multiple ligand probe dependent assay/polymerase chain reaction.

 Chromosomal microarray analysis to detect novel deletions and duplications associated with

syndromic and non syndromic CL/P.

 Whole exome sequencing to decipher novel monogenic causes of syndromic and non syndromic

CL/P.

• All this process will take 3-4 months as all the patients will be subjected to complete genetic

screening