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Cleft Lip

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Description: Cleft lip is a congenital facial deformity characterized by a physical split or separation of the upper lip.
Type: Cleft lip is a congenital malformation. The genetic transmission of cleft lip is complex and multifactorial, involving a combination of genetic and environmental factors. It does not follow a simple Mendelian inheritance pattern. Instead, multiple genes and their interactions, along with environmental influences, contribute to the development of the condition.
Signs And Symptoms: ### Signs and Symptoms of Cleft Lip:
1. **Visible Opening or Split**: An obvious physical gap or split in the upper lip, which may be unilateral (one side) or bilateral (both sides).
2. **Nose Shape Deformities**: Abnormalities in the shape of the nose, as the cleft may extend to the nasal cavity.
3. **Feeding Difficulties**: Challenges with sucking and eating, particularly in newborns.
4. **Speech Problems**: Potential speech and language delays, including difficulty with articulation.
5. **Dental Issues**: Misalignment of teeth or malformation of the gums.
6. **Ear Infections and Hearing Loss**: Increased risk due to associated problems with the Eustachian tube.
7. **Social and Emotional Impact**: Possible psychological effects due to appearance and speech difficulties.
Prognosis: Prognosis for cleft lip is generally very favorable with appropriate treatment. Surgical intervention is typically performed within the first few months of life, and additional surgeries may be needed as the child grows. With modern medical care, most children with cleft lip can achieve normal function and appearance.
Onset: Cleft lip is a congenital condition, meaning it is present at birth.
Prevalence: The prevalence of cleft lip varies by geographic region, ethnicity, and socioeconomic status, but it generally occurs in approximately 1 in 1,000 live births worldwide.
Epidemiology: Cleft lip and palate occurs in about 1 to 2 per 1000 births in the developed world.Rates for cleft lip with or without cleft palate and cleft palate alone varies within different ethnic groups.
According to CDC, the prevalence of cleft palate in the United States is 6.35/10000 births and the prevalence of cleft lip with or without cleft palate is 10.63/10000 births. The highest prevalence rates for cleft lip, either with or without cleft palate are reported for Native Americans and Asians. Africans have the lowest prevalence rates.
Native Americans: 3.74/1000
Japanese: 0.82/1000 to 3.36/1000
Chinese: 1.45/1000 to 4.04/1000
White Americans: 1.43/1000 to 1.86/1000
Latin Americans: 1.04/1000
Africans: 0.18/1000 to 1.67/1000Cleft lip and cleft palate caused about 3,800 deaths globally in 2017, down from 14,600 deaths in 1990.Prevalence of "cleft uvula" has varied from 0.02% to 18.8% with the highest numbers found among Chippewa and Navajo and the lowest generally in Africans.
Intractability: Cleft lip is not considered intractable. It can be effectively treated with modern surgical techniques. Most cases see significant improvement in both function and appearance after surgery, especially when performed by experienced medical professionals. Additional treatments may include dental care, speech therapy, and psychological support, leading to a generally positive long-term prognosis.
Disease Severity: Cleft lip severity can vary widely. It can range from a small notch in the lip to a significant separation that extends into the nose. The severity is generally categorized as mild, moderate, or severe, depending on the extent of the cleft and associated functional and aesthetic concerns.
Healthcare Professionals: Disease Ontology ID - DOID:9296
Pathophysiology: Cleft lip is a congenital deformity that occurs due to incomplete fusion of the maxillary and medial nasal processes during embryonic development, typically between the 4th and 7th weeks of pregnancy. This failure of fusion results in a physical gap or split in the upper lip, which can vary from a small notch to a large opening that extends into the nose. The exact cause involves a combination of genetic and environmental factors, such as nutritional deficiencies, exposure to certain chemicals or medications, or genetic syndromes. The pathophysiology encompasses disruption in the migration and proliferation of neural crest cells, which are essential for the formation of facial structures.
Carrier Status: Cleft lip is a congenital condition characterized by a split or opening in the upper lip, which can occur on one or both sides. Carrier status is typically not applicable for isolated cleft lip as it is often multifactorial, involving both genetic and environmental factors. Specific genetic syndromes associated with cleft lip may have identifiable carrier statuses, but for nonsyndromic cleft lip, carrier status is not generally defined.
Mechanism: Cleft lip is a congenital condition characterized by an opening or split in the upper lip. This occurs when the tissue that forms the lip does not join completely before birth.

**Mechanism:**
1. During embryonic development, the facial structures form between the 4th and 7th weeks of pregnancy. If the tissue that makes up the lip does not come together fully, a cleft lip occurs.
2. This failure can result in a small notch or an extensive opening that reaches the nose.

**Molecular Mechanisms:**
1. **Genetic Factors:** Multiple genes are involved in the formation of facial structures. Variations or mutations in these genes can disrupt the normal fusion process.
- **MSX1** (Msh homeobox 1): Related to craniofacial development.
- **IRF6** (Interferon regulatory factor 6): Involved in epithelial differentiation.
- **TP63** (Tumor protein p63): Plays a role in the development of limbs and craniofacial structures.

2. **Signaling Pathways:** Key signaling pathways implicated include:
- **BMP (Bone Morphogenetic Protein) Pathway:** Important for cellular differentiation and tissue formation.
- **FGF (Fibroblast Growth Factor) Pathway:** Involved in the proliferation and differentiation of cells.
- **SHH (Sonic Hedgehog) Pathway:** Critical for the patterning and growth of craniofacial structures.

3. **Environmental Factors:** Nutrient deficiencies, such as a lack of folic acid, and exposure to certain drugs, alcohol, or smoking during pregnancy, can interact with genetic predispositions to increase the risk.

Understanding these mechanisms provides insight into the complex interplay of genetic and environmental factors that contribute to the development of cleft lip.
Treatment: Cleft lip and palate is very treatable; however, the kind of treatment depends on the type and severity of the cleft.
Most children with a form of clefting are monitored by a cleft palate team or craniofacial team through young adulthood. Care can be lifelong and are looked after by craniofacial cleft teams often consist of: cleft surgeons, orthodontists, speech and language therapists, restorative dentists, psychologists, ENT surgeons and audio-logical physicians. Treatment procedures can vary between craniofacial teams. For example, some teams wait on jaw correction until the child is aged 10 to 12 (argument: growth is less influential as deciduous teeth are replaced by permanent teeth, thus saving the child from repeated corrective surgeries), while other teams correct the jaw earlier (argument: less speech therapy is needed than at a later age when speech therapy becomes harder). Within teams, treatment can differ between individual cases depending on the type and severity of the cleft.
Compassionate Use Treatment: Compassionate use treatment for cleft lip is typically considered when conventional surgical options are not viable or available. This may involve advanced surgical techniques or specialized care protocols that are still under investigation.

Off-label or experimental treatments might include the use of novel surgical materials, techniques, or growth factors to improve the healing process and cosmetic outcomes. Some experimental approaches also explore the use of tissue engineering and regenerative medicine to address the cleft more effectively. However, these treatments are generally subject to clinical trials and specific regulatory approvals.
Lifestyle Recommendations: Cleft lip is a congenital condition that requires medical intervention, usually surgery, to correct. Lifestyle recommendations for individuals with a cleft lip, particularly post-surgery, include:

1. **Nutrition**: Ensuring adequate nutrition can be challenging, especially for infants. Specialized feeding techniques or devices might be necessary to ensure proper intake of nutrients.
2. **Oral Hygiene**: Maintaining good oral hygiene is crucial. This includes regular dental check-ups and proper oral care routines to prevent infections and dental issues.
3. **Speech Therapy**: Engaging in speech therapy can be beneficial for improving speech development and articulation, which may be affected by the cleft lip.
4. **Regular Medical Follow-up**: Consistent follow-up appointments with healthcare providers, including surgeons, pediatricians, and other specialists, to monitor healing and ongoing health.
5. **Support Systems**: Joining support groups or networks for individuals and families dealing with cleft lip can provide emotional assistance and shared experiences.

Adopting these lifestyle recommendations can enhance overall well-being and improve quality of life for those affected by cleft lip.
Medication: Cleft lip is typically treated with surgical intervention rather than medication. However, supportive care may include pain management medications post-surgery and possibly antibiotics to prevent infection. Specific medications depend on individual cases and should be prescribed by a healthcare professional.
Repurposable Drugs: There are no widely recognized repurposable drugs specifically for cleft lip. Treatment typically involves surgical correction, which may be supported by multidisciplinary care including speech therapy, orthodontics, and psychosocial support.
Metabolites: Metabolites are small molecules involved in metabolism, acting as intermediates or end products of metabolic pathways. In the context of cleft lip, metabolic disruptions are not typically the primary focus, as it is primarily a congenital structural anomaly caused by genetic and environmental factors. Although specific metabolites associated with cleft lip are not well-defined, research into maternal nutrition and metabolic pathways, such as folate and vitamin B6, can be relevant since deficiencies in these nutrients during pregnancy have been linked to an increased risk of orofacial clefts.
Nutraceuticals: Nutraceuticals refer to foods or food components that provide health benefits beyond basic nutrition, but there is no established evidence to indicate their direct impact on cleft lip specifically. Cleft lip usually requires surgical intervention. Nutraceuticals may have general health benefits and could support overall well-being, but they are not a substitute for medical or surgical treatment of cleft lip.
Peptides: Peptides have shown potential in promoting wound healing and tissue regeneration in cleft lip surgical repairs. Studies involving bioactive peptides aim to improve the outcomes of these surgeries by enhancing tissue integration and reducing scarring. Nanotechnology can also play a role in cleft lip treatments. Nanoparticles may be used to deliver growth factors, drugs, or peptides directly to the surgical site, which can aid in the healing process and tissue regeneration. Research in these areas is ongoing to improve the efficacy and safety of treatments for cleft lip.