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