Handbook of Genetic Counseling/Opitz BBB - G Syndrome

Opitz BBB - G Syndrome (Opitz Oculo-Geito-Laryngeal Syndrome, Hypertelorism-Hypospadias Syndrome, Opitz-Frias Syndrome) Contracting Acknowledge prior phone contact What have you been told about why your were referred to genetics? What questions or concerns would you like us to address today? Set agenda for session Genetic Etiology Genetic heterogeneity X-linked loci mapping to Xp22.3 and possibly Xq22 Only males affected Sons of affected males can't be affected, daughters must be carriers Women have 50% chance for each pregnancy to inherit the mutation Sons of carrier women have 25% chance of being affected Autosomal dominant inheritance at 22q11.2 Molecular genetics Xp22.3 form is caused by mutation in MID1 gene Gene product is midin Midin is associated with microtubules throughout cell cycle Xq22 form is caused by mutation in MID2 gene (recently identified) Gene structure and protein product almost identical to MID1 Expressed in heart, but MID1 is not Unsure of clinical implications at this point Gene on chromosome 22 has not been determined yet Spontaneous mutations are rare Almost 100% penetrance Incidence Over 50 families reported in literature since 1965 Many families have not been reported Clinical Features Hypospadias (93%) Hypertelorsim (91%) Dysphagia (81%) - may be more common in X-linked form Developmental delay (43%) Kidney anomalies (42%) Laryngotracheal Esophageal cleft (LTE) (38%) Cleft lip and palate (32%) Strabismus (28%) Heart defects (27%) Patent ductus arteriosus Atrial septal defect Conotruncal anomalies Imperforate anus (21%) - may be more common in X-linked form Undescended testes (20%) Hypotonia - usually improves over time Other characteristic facial findings: Widow's peak hairline Ear abnormalities (72%) Low set Prominent or rotated ears Broad or flat nose Small chin Associated findings Urinary tract problems Large fontanels Underdevelopment of corpus collasum Lung abnormalities Lipomas Diastasis recti Usually clinically indistinguishable regardless of etiology Natural History Great variation in range of severity Males tend to be more severely affected than females Women usually only mildly affected Rarely symptoms are sever enough to cause death in infancy Usually normal growth and normal life span Testing Usually clinical diagnosis is most reliable Research testing for genes on X chromosome and chromosome 22 Mutations have been identified in some families with X-linked Opitz If mutation is identified, other at risk relatives can be tested Dr. Maximilian Muenke lab offers blood test for changes in MID1 Have found changes in 10 of 40 families studied Working to find gene on Xq22 Prenatal diagnosis can be offered once change in MID1 identified Polyhydramnios may be sign of affected fetus Some features may be observed on level II ultrasound after 22 weeks Surveillance, management, and treatment options No "treatment" available Surgical repair of heart defects, hypospadias, imperforate anus, LTE cleft, and some other findings when necessary OT, PT, and speech therapy when necessary Children with learning difficulties or mental retardation can obtain special services Differential Diagnosis FG syndrome Brachio-skeletal-genital syndrome Hypospadias and hypertelorism may be isolated or findings in many other syndromes Psychosocial Issues Guilt Difficulty dealing with child with many medical issues Fear of recurrence in future pregnancies Financial burden Changes in lifestyle, missed time at work to care for child with medical issues or mental retardation Support/Resources Pamphlet on Opitz Syndrome Vanderbilit University Medical Center DD-2205, MCN, Division of Medical Genetics Nashville, TN 37232-2578 Available on line: www.opitznet.org/modopitz.html Opitz Family Network PO Box 515 Grand Lake Colorado 80447 Phone: 970-627-8935 Email: opitznet@mac.com http://gle.egsd.k12.co.us/opitz/index.html National Organization for Rare Disorders Phone: 800-999-6673 http://www.nord-rdb.com/~orphan References Gorlin RJ, Cohen MM, Hennekam RCM. "Opitz oculo-genito-laryngeal syndrome." Syndromes of the Head and Neck. (2001): 988-990. Jones KL. "Opitz Syndrome." Smith's Recognizable Patterns of Human Malformation. (1997): 133-135. Opitz Family Network. (2002) http://gle.egsd.k12.co.us/opitz/index.html Notes The information in this outline was last updated in 2001.