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Disease Profile

Median cleft of upper lip with polyps of facial skin and nasal mucosa

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Pai syndrome; Median cleft of the upper lip-corpus callosum lipoma-midline facial cutaneous polyps syndrome; Median cleft of the upper lip-corpus callosum lipoma-cutaneous polyps syndrome

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 1993

Definition
A rare frontonasal dysplasia characterized by median cleft of the upper lip (MCL), midline polyps of the facial skin, nasal mucosa, and pericallosal lipomas. Hypertelorism with ocular anomalies are also observed, generally with normal neuropsychological development.

Epidemiology
Pai syndrome (PS) has been reported in 67 patients to date, however, the incidence seems to be underestimated.

Clinical description
PS presents at birth with a variable phenotype ranging from mild facial dysmorphism to more severe anomalies resembling frontonasal dysplasia. Most patients present with a marked hypertelorism with downward slanting palpebral fissures and may include a bifid nose in the most extreme cases. Midline cleft lip with midline nasal and facial polyps manifest generally as a bifid uvula with high palate, polyps are located over the nasal septum or extend from the nostril from an attachment to the nasal septum. These anomalies may lead to respiratory impairment, increased respiratory infections, speech impediments or early childhood difficulties in eating solids. Skin lipomas containing cartilage may be seen on the forehead. Ocular anomalies may include anterior segment dysgenesis, persistent papillary membrane, corneal leukoma, microcornea, posterior lenticonus, heterochromia iris and conjunctival lipoma. Coloboma of the iris has been reported. Neuropsychological development is usually normal, but some patients may present with epilepsy and impaired neuropsychological development. Sacral dimples may be observed at birth, and hypospadias has been reported in some male patients.

Etiology
The etiology of PS is unknown.

Diagnostic methods
PS is diagnosed strictly by clinical signs, the presence of a congenital nasal polyp plus one or more of the three following traits: MCL (with or without cleft alveolus), mid-anterior alveolar process congenital polyp and pericallosal lipoma. MRI may reveal pericallosal lipomas and an abnormal configuration of the third ventricle. An ophthalomogical exam is recommended.

Differential diagnosis
Differential diagnoses include Loeys-Dietz syndrome, oculocerebrocutaneous syndrome, frontonasal dysplasia, Goldenhar syndrome, as well as a variety of chromosomal anomalies.

Genetic counseling
One case of father to son transmission has been reported to date, but no recurrence in sibs has ever been reported. Recurrence risk in families with no history of PS is therefore thought to be low.

Management and treatment
Detection of potential oral or respiratory difficulties in newborns must be treated immediately. Multistage craniofacial surgery may be necessary in many cases. Surgical restoration of orbicular muscle continuity and excision of skin lipomas may be performed early in childhood, correction of the nasal pyramid should be performed after the pubertal growth spurt. In patients presenting with ocular anomalies, corneal or cataract surgery may improve vision in some cases, and optical iridectomy may be necessary in cases presenting with corneal leukoma. All patients should be regularly monitored for increases in intraocular pressure.

Prognosis
Both cosmetic and functional restoration of buccal and nasal anomalies is feasible and the prognosis is good for most patients.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Median cleft lip
Central cleft upper lip
0000161
Midline central nervous system lipomas
0006866
Nasal polyposis
0100582
Skin tags
0010609
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin

[ more ]

0001482
30%-79% of people have these symptoms
Abnormal oral frenulum morphology
0000190
Bifid uvula
0000193
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Telecanthus
Corners of eye widely separated
0000506
5%-29% of people have these symptoms
Aplasia/Hypoplasia of the corpus callosum
0007370
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Encephalocele
0002084
Iris coloboma
Cat eye
0000612
Midline defect of the nose
0004122
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Broad forehead
Increased width of the forehead
Wide forehead

[ more ]

0000337
High palate
Elevated palate
Increased palatal height

[ more ]

0000218

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Median cleft of upper lip with polyps of facial skin and nasal mucosa. Click on the link to view a sample search on this topic.