Pai syndrome (ORPHA:1993)
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 ophthalmological 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.

                            Last update: 
                            October 2019


                            - Expert reviewer(s): 
                            Dr Damien LEDERER