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Handbook of Genetic Counseling/Opitz BBB - G Syndrome

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Opitz BBB - G Syndrome

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

Contracting

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  • 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

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  • 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

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  • Over 50 families reported in literature since 1965
  • Many families have not been reported

Clinical Features

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  • 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

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    • 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

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    • 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

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    • 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

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  • FG syndrome
  • Brachio-skeletal-genital syndrome
  • Hypospadias and hypertelorism may be isolated or findings in many other syndromes

Psychosocial Issues

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  • 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

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  • 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

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  • 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

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The information in this outline was last updated in 2001.

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