Malpuech facial clefting syndrome

Overview

A very rare syndrome characterized by mental and physical retardation, wide set eyes, genital abnormalities and a characteristic facial cleft.

Symptoms

* Mental retardation * Physical retardation * Facial cleft * Widely spaced eyes * Urogenital anomalies

Causes

* Cleft lip with or without cleft palate –Incidence 1/500–1/2,500 –Highest incidence among Native Americans –Defects are unilateral in 80% –More common in boys –Pathogenesis is multifactorial * Isolated cleft palate –Incidence 1/2,000 –More common in girls * Pierre-Robin sequence –Micrognathia, glossoptosis (posterior displacement of the tongue to pharynx), and cleft palate –Incidence 1/2,000–1/30,000 –Mortality 2.2–26% * Syndrome-associated cleft lip with or without cleft palate –Accounts for 30% of cases –Over 300 syndromes include this phenotype –Stickler syndrome (25%): Pierre-Robin sequence with severe progressive myopia and arthritis in young adulthood –Velocardiofacial syndrome (15%): Slender hands and fingers, cardiac defects (TOF, VSD, right aortic arch), prominent nose; deletion of 22q11.21 –DiGeorge syndrome: Thymic hypoplasia, hypoparathyroidism, cardiac defects (truncus arteriosus, interrupted aortic arch) same spectrum at velocardial facial with same deletion of 22q –Trisomy 13: Microcephaly, cutis aplasia, polydactyly cardiac defects –Trisomy 18: Low-set ears, clenched hands, rocker bottom feet, cardiac defects –van der Woude syndrome: Cleft palate associated with lip pits * Cause associated with maternal exposure to corticosteroids, phenytoin, valproic acid, thalidomide, alcohol, cigarettes, dioxin, or retinoic acid; and maternal diabetes mellitus, hormone imbalance, and vitamin deficiency

Diagnosis

o History –Prenatal and birth history –History of prenatal drug/medication use –Family history of cleft lip or palate, or other birth defects –Ethnic background * Physical exam –Location and extent of the defect –Presence or absence of submucosal cleft palate (must be palpated, because it may not be visible beneath the oral mucosa) –Dental examination –Cardiac examination + Studies –Syndromic cleft lip with or without cleft palate is detected at fetal ultrasound in 38% of cases –Nonsyndromic clefting is difficult to see on fetal ultrasound –Screening Echo for cardiac anomalies and –Chest X-ray for presence of thymus o Screenings –Neonatal and periodic hearing screening –Calcium level and immunoglobulins for DiGeorge o Dental and speech evaluations

Treatment

o Neonatal support is largely nutritional –Patients with velopharyngeal insufficiency are at risk for aspiration –Breastfeeding may or may not be possible depending on the location and size of the defect –Specialized bottles and nipples may be required to accomplish adequate feeding * Surgical correction (usually in 2–4 stages) with surgical priorities being prevention of regurgitation and aspiration, enabling of speech production, and cosmetic result –In patients with delayed surgical correction, a prosthesis may be necessary to compensate for velopharyngeal insufficiency and to enhance speech development –Speech therapy –Monitoring for otitis media –Referral to a geneticist for genetic testing and consideration of risk with subsequent pregnancies