Cleft lip and palate is the most common congenital abnormality seen in the Department of Plastic Surgery, Singapore General Hospital. A total of 461 operative cases seen over a period of 5 years (1977 to 1981) is analysed. There is a relatively high incidence in the Singapore population of 2.0 per 1000 live births. In both cleft lip and cleft palate deformities, there is no significant difference in the sex distribution. The cleft patterns show that 78% of the cases are unilateral clefts, 53% are left sided, 25% are right sided and 22% of the cases are bilateral clefts.
The Combined Cleft Clinic at the University Hospital, Kuala Lumpur was organised in 1992. The team consists of Plastic Surgeon, Orthodontists, Speech therapist, Ear, Nose and Throat Surgeon, Audiologist, medical officers and the nurses. We attend the clinic on a regular basis. Specialists from other medical and dental disciplines as well as the members of the Cleft Lip and Palate Association of Malaysia (CLAPAM) do occasionally participate in this set-up.The team members formulate treatment plans for each cleft patient, monitor the patient's growth and development and manage the patient at different stages according to the individual needs. To date, the idea of team approach and an establishment of a centre towards management of cleft patients seem to be the most ideal as the patients are benefiting total treatment and care from various specialists from only one place. The experience of University Hospital as a centre for cleft patients is discussed.
Several studies have shown evidence for the contribution of interferon regulatory factor 6 (IRF6) variants to the risk of nonsyndromic oral clefts in Asians; however, this has not included the Malay population. The current study attempts to address this research gap using allele and haplotype transmission disequilibrium analyses. The results showed a strong transmission distortion for multiple haplotypes to patients with nonsyndromic cleft lip with or without cleft palate. Haplotypes carrying the 243 bp allele of D1S2136 and common alleles at the rs861019 and rs2235371 were over-transmitted to patients. By contrast, haplotypes consisting of the 251 bp allele of D1S2136 and the rare allele at rs2235371 were more under-transmitted. Furthermore, several variants and haplotypes showed excess maternal transmission, but none of them attained statistical significance in maternal relative risk analyses. In contrast, a significant child genotype effect was observed for several haplotypes, indicating fetal genotype could be the major genetic contribution rather than maternal genotype. The present study therefore further supports a role for IRF6 variants in clefting in this Southeast Asian population. Overall, Asian genetic backgrounds are most likely more susceptible to the haploinsufficiency of IRF6 variants. These variants may contribute to the condition either themselves, or they may be in linkage disequilibrium with other casual variants.
We describe a chromosome 6 uniparental disomy (UPD6) in a boy, discovered during a screening for the genetic cause of cleft lip and palate. In the medical literature, almost all documented cases of UPD6 are paternal in origin, and only four were maternal. We present here a report of complete maternal chromosome 6 uniparental heterodisomy. Haplotype analysis was performed using highly polymorphic short tandem repeat (STR) markers that span both arms of chromosome 6. Analysis of these markers revealed the presence of two maternal alleles but no paternal allele, indicating an instance of maternal uniparental heterodisomy. Chromosome analysis of peripheral blood lymphocytes confirmed a normal male karyotype. Advanced maternal age at the time of the infant's birth and heterodisomy of markers around the centromere favors a meiosis-I error. No specific phenotype has been reported for maternal UPD6. Therefore, the cleft lip and palate in the present case probably occurred due to other risk factors. This report provides further evidence that maternal UPD6 has no specific clinical consequences and adds to the collective knowledge of this rare chromosomal finding.