There are some 400 known syndromes associated with cleft lip and/or palate. A study (1970) ((Fraser, F. C. (1970) The genetics of cleft lip and palate. American Journal of Human Genetics. 22:336-352.)) by F. C. Fraser noted that approximately 3% of all cases of clefting were associated with known syndromes. A Danish study (1988) (( Jensen, B. L. et al. (1988) Cleft Lip and Palate in Denmark, 1976-1981: Epidemiology, variability, and early somatic development. Cleft Palate Journal. 25:258-269.)) indicated a figure of 4.3% and concluded that this figure probably underestimated the true frequency with which other anomalies were associated with facial clefting. A study carried out in Singapore (1999) ((Yi, N.N., Yeow, V.K., Lee, S.T. (1999) Epidemiology of cleft lip and palate in Singapore–a 10-year hospital-based study. Ann Acad Med Singapore Sept, 28(5):655-9.)) indicated that associated congenital deformities occurred in 1.5% of the total cleft population.
22q11.2DS is the most common genetic syndrome associated with palatal clefts and congenital velopharyngeal dysfunction. The most commonly occurring palatal anomalies are submucous and occult submucous cleft palate.
These anomalies, particularly the occult submucous, are difficult to diagnose in the absence of nasendoscopic evaluation and often go undetected until later childhood for assessment of velopharyngeal dysfunction. It is recommended that the closure of the palate is done early and before the development of meaningful speech for improved outcome. Therefore, individuals who are diagnosed with 22q11.2DS should be assessed by a cleft-palate team as early as possible.
The hypernasal speech associated with 22q11.2DS was described in the 1950s. Approximately 75 per cent of individuals with 22q11.2DS have hypernasal speech and 62 per cent have articulation problems. In the majority of cases, the onset of speech is delayed, with more significant difficulties associated with expressive language compared to receptive language abilities. Intensive articulation therapy in conjunction with palatal surgery is essential to restore normal speech and resonance.
Apert syndrome (AP) is a rare genetic disorder which involves distortion of the head and face and webbing of the hands and feet. Characteristics include prematurely fused cranial sutures, sunken mid-face, fused fingers and toes, short wide head, high prominent forehead, flattened back of skull, and prominent eyes. About 30% of children diagnosed as having AP also have a cleft palate. Other associated problems may include ear infections, problems with vision, and noisy breathing. ((FACES: The National Craniofacial Association (USA) http://www.faces-cranio.org/Disord/Apert.htm [link verified 09/06/2014]))
Early surgery to separate the plates in the skull releases pressure and allows for brain growth. A surgical procedure known as the LeFort procedure is carried out when the child has grown substantially to correct the concave appearance of the mid-face region. Surgery is also carried out to separate the fingers, though it is not usually carried out to separate the toes unless they inhibit movement.
AP is caused by a genetic mutation in the FGFR2 gene on chromosome 10 early in pregnancy. Studies suggest that AP occurs more often in children with older fathers. AP occurs in 1 in 100,000 to 160,000 live births. ((Special Child by The Resource Foundation for Children with Challenges (RFCC) (USA) http://www.specialchild.com/archives/dz-020.html [link verified 09/06/2014]))
Pierre Robin Sequence
Pierre Robin Sequence (sometimes referred to as Pierre Robin Syndrome) is a common variation of simple cleft palate. The baby has a combination of cleft palate, a small underdeveloped lower jaw (retrognathia) and a falling of the tongue into the back of the mouth (glossoptosis). This never occurs in combination with cleft lip and is never inherited or passed on.
The incidence is one child in every 30,000. The milder form of the sequence is relatively common whereas the more developed form is quite rare where the baby may have some problems breathing due to the tongue partially obstructing breathing because of its position at the back of the mouth.
It is commonly accepted that the cause of this sequence is that the baby has been cramped in the womb with the head pressed more firmly onto the chest than usual. This physically holds back the lower jaw growth and pushes the tongue up into the roof of the mouth, stopping the natural closure of the palate in the early days of development.
This would explain the fact that almost all the babies’ jaws catch up in growth over the first year of life and that this is not an inherited condition.
Repair of the cleft palate is often carried out at 9 or 12 months of age when the jaw has grown forward. This is to diminish any chance that if the operation is carried out earlier it might push the tongue back further into the back of the throat bringing on breathing problems.
A small number of babies who have breathing problems at birth because the jaw is so small may need nursing on their face in a special frame for some time while the jaw develops and normal breathing is restored.
It is important that babies with breathing problems are seen by a paediatrician and a plastic surgeon.
Speech and Feeding
The child may see a speech and language therapist in the early stages if there are feeding difficulties. Some Pierre Robin babies have difficulty in getting their feeding established due to their cleft and small mandible. If this is not the case, parents should ensure that the child is taken to the speech and language therapist at about the age of 8 months. The therapist will not be able to do much direct work with the child at this stage but can advise parents on how best to develop communication directly. A referral to a speech therapist is not always automatic and often the parent will have to request one.
Often a child with Pierre Robin Sequence will have a hearing problem which can have an effect on speech and language development. It is important to have the child assessed for hearing loss at an early age so that the appropriate treatment can be carried out.
With the help of the plastic surgeon, paediatrician, speech therapist, audiologist, ENT surgeon and the dentist, the child with Pierre Robin Sequence can look forward to a bright future.
Stickler syndrome (SS) is a connective tissue disorder, and is associated with problems of vision, hearing, facial and cleft palate, the joints and the heart. ((SIP (Stickler Involved People) (USA) )) Problems with the eyes include near sightedness (myopia), astigmatism, and cataracts, with a substantial risk of retinal detachment. The associated heart problem is known as Mitral Valve Prolapse. Joint trouble is as a consequence of having hyperextinsible joints resulting in pain and stiffness as the child gets older. Osteoarthritis typically develops in the third or fourth decade. ((Snead, MP, Yates, JR. Clinical and molecular genetics of Stickler syndrome. Journal of Medical Genetics, May 1999, 36(5):353-9. Fulltext at http://jmg.bmj.com/cgi/content/full/36/5/353 (accessed 30 June 2007) ))
Patients usually do not have all of the symptoms and indeed SS proves difficult to diagnose because so few of the symptoms may manifest themselves. The majority of families with SS have mutations in the COL2A1 gene. (( Ref:2))
There is a 50% chance of an affected parent passing on the gene. ((The Boys Town Research Registry for Hereditary Hearing Loss, Boys Town National Research Hospital, Omaha, Nebraska, USA. http://www.boystownhospital.org/Hearing/info/genetics/syndromes/stickler.asp (accessed 30 June 2007) )) An estimated 1 in every 10,000 persons has Stickler syndrome, and many may not even know that they have it.
Irish families seeking further information should contact:
Theresa Corrigan, Tel. 042 9665548
Treacher Collins Syndrome
Also called mandibulofacial dysostosis, Treacher Collins syndrome (TCS) is an ‘autosomal dominant disorder… that results from loss-of-function mutations in the gene TCOF’. ((Dixon, J. et al. Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, treacher collins syndrome. Human Molecular Genetics 12 Jun 2000, 9(10):1473-80)) It affects the size and shape of the ears, cheekbones and jaw. The following characteristics will display to varying degrees: downslanting eyes, notched lower eyelids, underdeveloped cheek and jaw bones, and underdeveloped, malformed and/or prominent ears. Cleft palate often occurs with TCS. Breathing problems will also exist which may necessitate the insertion of a tracheostomy tube to assist breathing.
Approximately 40% of children will have hearing loss in both ears. TCS can vary in severity from something that may go unnoticed to the more severe case displaying many of the symptoms. As the child grows, most of associated problems are alleviated. Closure of the soft palate will occur at around 3 months, the cheeks and eyelids may be addressed at about 3 years of age, and ear deformities are addressed at about 5-7 years of age.
TCS occurs in approximately 1 of every 10,000 births. In about 40% of cases one parent has what is believed to be the affected gene. There is a 50% chance of the children of an affected parent having TCS.
Velocardiofacial syndrome (VCFS) is the syndrome most commonly associated with a cleft palate, most usually cleft of the soft palate. A cleft lip may also occur. The incidence of VCFS is approximately 1:2000 of live births, and it occurs in 8% of cleft palate cases ((Figures from the Velo-Cardio-Facial Syndrome Educatioal Foundation in Syracuse, New York, USA. www.vcfsef.org/ [link verified 07 May 2007])).
VCFS is also known as Shprintzen syndrome after Dr. Robert Shprintzen who first described it in 1978. Though the two terms are often used interchangeably, DiGeorge sequence and VCFS are clinically distinct but overlapping conditions.
The cause of VCFS is not known, although it is known to be a genetic disorder. Though the gene (or genes) responsible has not been identified, what has been ascertained is that a small part of chromosome 22, known as 22q11, is missing in the vast majority of individuals – approximately 82% ((According to Peter Scambler, M.D. Institute of Child Health, London, available at http://www.crosslink.net/~marchett/vcfs/gene1.htm [accessed 29 June 2000, link broken 07 May 2007])) who are diagnosed as having VCFS.
Aside from cleft palate, there are up to 184 other anomalies commonly associated with VCFS, including heart defects, unique facial characteristics (elongated face, almond-shaped eyes, small ears, wide nose), speech and feeding problems, middle ear infections, and learning difficulties. Not all anomalies are present in the child, nor is any one anomaly present in all cases. The features with which the child is born do not get progressively worse over time.
VCFS is an autosomal disorder, which means that only one parent needs to have the gene in order to pass it on to their offspring. In the case of one of the parents having the gene, there is a 50% chance of VCFS being passed on to the offspring. However, only 10-15% of cases are inherited ((Figures from the National Institute on Deafness and other Communication Disorders, part of the National Institute of Health in Bethesda, Maryland, USA. http://www.nidcd.nih.gov/health/voice/velocario.htm [verified 07 May 2007])). There is no difference in the incidence of VCFS between the sexes.