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Cleft lip and/or palate (non-syndromic)
This condition affects the face and mouth, impacting feeding, speech, and appearance. It is one of the most common birth variations, affecting around 1 in 700 babies born in the UK, and is typically managed through surgery and multidisciplinary care.
Overview
Cleft lip and/or palate (CL/P) is a condition that occurs when parts of the face, specifically the upper lip and/or the roof of the mouth (palate), do not fuse together completely during the early stages of a baby's development in the womb. When only the lip is affected, it is called a cleft lip. When only the palate is affected, it is a cleft palate. If both are affected, it is a cleft lip and palate. Non-syndromic CL/P means that the cleft occurs as an isolated condition, without other birth variations or symptoms that would suggest an underlying genetic syndrome [PMID:33678564].
This condition can vary widely in its presentation, from a small notch in the lip to a complete separation extending into the nose and/or along the entire palate. Although it is a physical difference present from birth, advancements in medical and surgical care mean that most individuals with non-syndromic CL/P can achieve excellent outcomes with appropriate management.
Symptoms & clinical features
The primary clinical features of non-syndromic cleft lip and/or palate are visible differences in the upper lip and/or the palate. A cleft lip may appear as a small notch or a complete separation that extends to the nostril. A cleft palate involves an opening in the roof of the mouth, which can affect the hard palate (bony front part), the soft palate (muscular back part), or both. Sometimes, a cleft palate may not be immediately visible, especially if it only affects the soft palate muscles under the mucous membrane, known as a submucous cleft [PMID:33261680].
Beyond the visible differences, some common challenges associated with CL/P can include difficulties with feeding in infants, as the oral cavity's structure may prevent effective sucking. Speech development can also be affected, potentially leading to nasal-sounding speech or difficulties forming certain sounds. Dental issues, such as missing, malformed, or misaligned teeth, are also frequently observed. Additionally, individuals with cleft palate may be more prone to middle ear infections due to issues with Eustachian tube function, which can sometimes impact hearing [PMID:33261680].
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Affected organs
Non-syndromic cleft lip and/or palate primarily affects the anatomical structures of the head and neck, specifically those involved in forming the upper lip and the roof of the mouth. This includes the maxilla (upper jaw bone), the premaxilla (small bone at the very front of the upper jaw), and muscles and tissues of the upper lip and palate.
The condition can also indirectly affect the ears, leading to a higher susceptibility to middle ear infections (otitis media) due to impaired function of the muscles that open the Eustachian tube. This tube helps drain fluid from the middle ear. Speech centres in the brain are not directly affected, but speech production difficulties are a common consequence due to altered oral anatomy.
Risks & severity
The severity of non-syndromic cleft lip and/or palate can range from a minor notch in the lip to a wide, complete separation of both the lip and palate. The extent of the cleft often determines the complexity of surgical repair and the degree of associated functional challenges, such as feeding and speech difficulties.
Non-syndromic CL/P is considered a multifactorial condition, meaning it is influenced by a combination of genetic and environmental factors. Its exact prevalence is approximately 1 in 700 live births in the UK. While serious in its impact on development and quality of life without intervention, it is generally not life-threatening. Individuals with non-syndromic CL/P typically have a normal life expectancy. For families with one child affected, the chance of another child having a cleft may be slightly increased compared to the general population, although specific risks vary based on genetic and environmental factors [PMID:31405822].
Genetic causes
Non-syndromic cleft lip and/or palate is described as a polygenic or complex condition. This means it is influenced by multiple genes acting together, often in combination with environmental factors. Many genes have been suggested to play a role in the development of CL/P, and research continues to explore these contributions.
Among the genes that have been associated with an increased risk of non-syndromic CL/P are IRF6, MSX1, and VAX1. The IRF6 gene provides instructions for making a protein that is important for the development of facial structures, particularly during the fusion of the lip and palate. Changes in IRF6 are known to be a significant genetic risk factor for CL/P. MSX1 is involved in tooth development and craniofacial morphogenesis. Variants in MSX1 can affect palate formation. VAX1 also plays a role in early embryonic development, including the formation of facial structures. Pathogenic variants in these genes are thought to disrupt a complex network of developmental processes, leading to the formation of a cleft.
Inheritance pattern
Non-syndromic cleft lip and/or palate follows a polygenic or complex inheritance pattern. This means that unlike conditions caused by a change in a single gene, CL/P arises from the combined effects of several genetic variations, often interacting with various lifestyle and environmental factors. Because of this complex inheritance, it does not follow simple Mendelian patterns, such as autosomal dominant or recessive inheritance.
In most cases, parents who have a child with non-syndromic CL/P do not carry a single 'cleft gene' that they would pass on directly. The risk to close relatives is increased compared to the general population but is generally low. For example, if one child has CL/P, the chance that a subsequent child will also have it is typically around 2-5%. Genetic counsellors can provide personalised risk assessments based on individual family history.
Diagnosis & testing
The diagnosis of cleft lip is typically made at birth through a visual examination. A cleft palate, particularly a submucous cleft, might be diagnosed later if feeding difficulties, characteristic speech patterns, or recurrent ear infections arise. In some cases, a cleft lip and/or palate may be detected during prenatal ultrasound scans, especially around 18-20 weeks of pregnancy during the anomaly scan.
After birth, a specialist team, often including a paediatrician, plastic surgeon, and geneticist, will confirm the diagnosis and assess the extent of the cleft. Genetic testing is not routinely performed for isolated non-syndromic CL/P within the NHS, as it is a multifactorial condition not typically caused by a single gene variant. However, if there are additional issues or features that suggest an underlying genetic syndrome, referral to a clinical genetics service via a Genomic Medicine Centre may be considered. The NHS Genomic Medicine Service offers diagnostic testing, and relevant R-codes for syndromic clefting are available, though less so for isolated non-syndromic cases.
Management & lifestyle
Management of non-syndromic cleft lip and/or palate in the UK is provided through specialised NHS Cleft Teams. These multidisciplinary teams consist of plastic surgeons, oral and maxillofacial surgeons, orthodontists, speech and language therapists, specialist nurses, genetic counsellors, and psychologists. The typical approach involves a series of surgical procedures to repair the lip and/or palate, usually performed in stages during early childhood.
Follow-up care is long-term and covers various aspects, including ongoing speech and language therapy, orthodontic treatment to align teeth and jaws, and monitoring for hearing issues. Emotional and psychological support for the individual and their family is also an important component of care. The goal of management is to ensure optimal cosmetic appearance, speech function, hearing, and dental health. Genetic counselling is available through the NHS to discuss recurrence risks and provide information to families.
UK care pathway
In the UK, individuals diagnosed with cleft lip and/or palate are referred to one of the regional NHS Cleft Teams. These highly specialised teams provide comprehensive, coordinated care from diagnosis through to adulthood. Referrals often come from GPs, midwives, or paediatricians. Genetic counselling, offered through NHS Genomic Medicine Services, is available to families to discuss the inheritance patterns and recurrence risks associated with the condition. While R-codes exist for genetic testing in cases where a syndromic cause is suspected, non-syndromic CL/P is generally managed clinically rather than through specific diagnostic genetic testing.
Frequently asked questions
What causes non-syndromic cleft lip and/or palate?
Non-syndromic cleft lip and/or palate is considered a multifactorial condition. This means it arises from a complex combination of genetic factors, involving multiple genes like IRF6, MSX1, and VAX1, together with certain environmental influences like maternal nutrition, smoking, or some medications during pregnancy.
Will my child need multiple surgeries?
Yes, typically, children with cleft lip and/or palate require a series of surgical procedures. Cleft lip repair is usually done around 3-6 months of age, and cleft palate repair often follows between 6-12 months. Further surgeries may be needed later in childhood or adolescence for speech improvement, dental alignment, or cosmetic adjustments.
Will my child's speech be affected?
Speech development can be affected in children with cleft palate due to the altered structure of the mouth. The NHS Cleft Team includes speech and language therapists who work with children from an early age to support their speech development, and many achieve clear speech with therapy and surgery.
What are the chances of having another child with a cleft?
Since non-syndromic cleft lip and/or palate has a complex inheritance, the risk of recurrence for future children is generally low, but slightly higher than in the general population. A genetic counsellor can provide a more personalised risk assessment based on your family history.
Can cleft lip and/or palate be detected before birth?
Sometimes, a cleft lip may be detected during a routine prenatal ultrasound scan, typically around 18-20 weeks of pregnancy. Observing a cleft palate with ultrasound can be more challenging, especially if it is isolated without a cleft lip.