Clefts occur when the upper lip and the palate (the roof of the mouth) fail to join normally when the baby is in the womb. CLEFT researchers have been looking into a rare disorder of palate development that was found in a family from Egypt five years ago and have since been able to identify the cause of this as being due to a variant in a gene called FOXF2. This is an amazing and exciting discovery and the findings have just been published in a paper written by Dr Rimante Seselgyte (pictured above) and Professor Philip Stanier and colleagues, published in the Journal of Dental Research.

In 2015, Youssef (age 3) was brought to London by his family to see Mr Brian Sommerlad, CLEFT Chairman and plastic surgeon, at Great Ormond Street Hospital.

Youssef had a history of sometimes bringing milk up through his nose while breastfeeding in infancy and was showing signs of not meeting his speech and language milestones, along with hypernasality (increased airflow through the nose which causes abnormal resonance in the voice). Speech delays are common in children with cleft palates, along with problems of hearing and orthodontics, but can usually be overcome with an operation to repair the palate along with speech therapy.

Mr Sommerlad noted that the boy's uvula (the dangling bit at the back of the soft palate) was missing and there were some other abnormalities of the opening from the mouth to the throat. Youssef was successfully operated on and during subsequent appointments held in both the UK and Egypt, it came to light that seven other members on his father's side of the family had the same condition. It is always interesting to researchers when multiple family members present with the same condition and this family is of no exception. CLEFT researchers realised that the family history could be highly significant and a project to examine the family’s genes was undertaken. It was confirmed that this was inherited condition and data from the whole family was to pinpoint the causal gene.

Following the surgery and some speech therapy in Egypt, Youssef's speech is now normal and he is doing well at school.

This important piece of work has taken four years to research and identify and is another piece in the jigsaw trying to identify the causes of clefts. It is part of a global effort to identify the genes responsible for congenital abnormalities. Professor Stanier said "The discovery of a new gene responsible for palate development is very exciting. It will be important to find out if further families share a similar palate defect as a consequence of variants in this gene."

The FOXF2 research is one of the many projects currently funded by CLEFT, paid for with money raised by our donors and fundraisers.

PAPERS PUBLISHED

See a summary of the findings in the Journal of Dental Research vol.98, 6: pp. 659-665. , First Published March 27, 2019 'Disruption of FOXF2 as a Likely Cause of Absent Uvula in an Egyptian Family.

Seselgyte, D. Bryant, C. Demetriou, M. Ishida, E. Peskett, N. Moreno, D. Sell, M. Lees, M. Farrall, G.E. Moore, B. Sommerlad, E. Pauws, P. Stanier

READ SUMMARY