Handbook of Genetic Counseling/Opitz BBB - G Syndrome

Opitz BBB - G Syndrome

(Opitz Oculo-Geito-Laryngeal Syndrome, Hypertelorism-Hypospadias Syndrome, Opitz-Frias Syndrome)

Contracting

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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.