# 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.