• Description

  • An X-linked recessive mental retardation syndrome.
  • Characterized by:
    • Dysmorphic features: relative macrocephaly, hypertelorism, downslanted palpebral fissures, prominent forehead with frontal hair upsweep, broad thumbs, and halluces.
    • Hypotonia, constipation, partial agenesis of the corpus callosum.
    • Some patients exhibit sensorineural hearing loss, joint laxity evolving into joint contractures.
    • Hyperactivity and talkativeness are common.

• History

  • Initially described as 'FG syndrome' by Opitz and Kaveggia in 1974, using the initials of patients' surnames.

• Genetic Heterogeneity

  • Different forms of 'FG syndrome' identified:
    • FGS2: Mutation in the FLNA gene (Xq28).
    • FGS4: Mutation in the CASK gene (Xp11).
    • FGS3: Mapped to Xp22.3.
    • FGS5: Mapped to Xq22.3.
  • MED12 gene mutation should be reserved for Opitz-Kaveggia syndrome.

• Clinical Features

  • Initial descriptions included mental retardation, large head, imperforate anus, congenital hypotonia, and partial agenesis of the corpus callosum.
  • Additional features include short stature, joint contractures, seizures, gastrointestinal defects, and congenital heart defects.
  • Features such as broad great toes and frontal upsweep of hair have been observed in unrelated families.
  • Associated features: sensorineural deafness, severe constipation, telecanthus, hypertelorism, macrocephaly, characteristic facial appearance, and personality traits.
  • Behavioral characteristics include socially oriented and attention-seeking behaviors similar to Williams syndrome.

• Diagnosis

  • Defined as an X-linked multiple congenital anomaly-cognitive impairment disorder caused by the R961W mutation in the MED12 gene.
  • Clinical criteria include small ears, characteristic facial features, congenital anomalies, and a distinctive personality.

• Mapping

  • Linkage analysis identified linkage to DXS441 at Xq13, confirming genetic heterogeneity.
  • Inversion inv(X)(q12q28) associated with FG syndrome in some families.

• Molecular Genetics

  • MED12 gene, located at Xq13, influences thyroid function and is implicated in X-linked mental retardation.

Reference

Online Mendelian Inheritance in Man (OMIM). (2024). OPITZ-KAVEGGIA SYNDROME. Retrieved June 28, 2024, from https://www.omim.org/entry/305450