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Handbook of Genetic Counseling/FG Syndrome

< Handbook of Genetic Counseling

FG Syndrome

Introduction and Contracting

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  • Can you explain to me in your own words why you were referred to genetics?
  • What questions if any do you have for us today
  • What are your main concerns at this time
  • Outline the session and what will occur
    • Medical and developmental history
    • Family history (pedigree)
    • Dr. will physically examine him
    • We will explain any conclusions if any that we have reached and discuss what we think might be the explanation for the concerns and problems

Pedigree

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  • Basic 3 generation pedigree unless specific findings come up and may need explore maternal side further due to X-linked pattern of FG syndrome
  • birth defects
  • pregnancy loss
  • poor muscle tone
  • chronic constipation
  • hearing loss
  • vision problems
    • kidney problems
    • problems with the digestive tract
    • other chronic health problems
    • mental retardation of learning difficulties
    • large head size
    • broad thumbs and toes
    • fingernails that grow over tips of fingers
    • behavioral problems

Overview of FG

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  • X-linked recessive condition
  • First described 1974 by Drs. John M. Opitz and Elizabeth G. Kaveggia
  • Named after initials of first patients described
  • Multiple congenital anomaly/mental retardation syndrome
  • Characterized by MR, macrocephaly, congenital hypotonia, macrocephaly, facial dysmorphism and anomalies of the digestive tract
  • No features are pathognomonic

FG syndrome physical characteristics

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  • prenatal oligohydrammios
  • High degree of variability of physical features
  • Hypotonia with joint hyperlaxity evolves into spasticity with joint contractures later in life
  • chronic constipation is a distinctive major finding in FG (usually resolves during mid-childhood)
  • hearing loss
  • vision problems
  • genital abnormalities (cryporchidism)
  • respiratory problems
  • congenital heart defects uncommon but include hypoplastic left heart, small VSD; VSD and mitral and aortic valve defect (Opitz, 1988)
  • agenesis of the corpus collosum
  • anteriorly positioned or imperforate anus
  • kidney problems
  • large head
  • broad thumbs and toes
  • characteristic fingerprint patterns
  • webbed fingers and toes
  • skeletal defects (occasionally including craniosynostosis and scoliosis)
  • sacral pit
  • tethered cord and Chiari I malformations
  • wide set eyes
  • broad nasal bridge
  • low set simple ears that are small, rounded, and protruding
  • thin upper lip and fuller lower lip
  • cowlicks and a widow's peak hairline

Developmental and behavioral features of FG syndrome

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  • delayed acquisition of speech and motor skills
  • Individuals with FG Syndrome tend to be outgoing, talkative, and crave lots of attention
  • May be easily frustrated and are prone to temper tantrums
  • Hyperactivity and impulsiveness have been reported
  • Most function in mild to moderate range of MR other reports state it is usually severe MR
    • Some clinicians feel MR is universal finding in FG, but others feel there is a wide range of cognitive ability and some are in normal range
  • Often language skills are underdeveloped
  • "Autistic-like" behaviors have been discussed. This may be due to a common trait of the FG Syndrome--- sensory integrative dysfunction. However, they are not believed to be autistic
    • Frequent fascinations with mechanical objects and toys, tendency to self-absorption

Life expectancy

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  • Death during infancy as high as 1/3 of patients due to bronchopulmonary problems and/or heart defects
  • "Once they survived infancy death is rare"

Genetics

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  • presumably due to mutations on the X chromosome
  • presumed to cause disruption in the development of the fetus
    • X-linked recessive
    • Heterogeneous condition
    • mapped one gene (FGS1) to Xq13 (Briault et al.) in some families using linkage analysis
    • evidence for another gene locus (FGS2) at Xq28 or Xq11q12 based on fact these are breakpoints of an inversion that segregate with FG phenotype (Briault et al., 2000)
    • Dr. Opitz lists a potential third gene (FGS3) at Xp22.3 (Opitz, Sep, 2001)
    • 9 candidate genes excluded in three families (A Lossi, A Fatima, S Briault, C Moraine, C Schwartz, 2000)

Diagnosis

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  • Clinical diagnosis
  • No molecular testing available (Opitz, 2001)
  • Diagnosis based on clustering of symptoms with no symptom being pathognomonic
  • Some believe it is not uncommon and may account for many cases of unexplained X-linked MR

Genetic Testing

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  • Linkage analysis is possible in large families with multiple affected family members
  • Prenatal testing and carrier testing only possible through such linkage analysis described above

Differential Diagnosis

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  • Fragile X syndrome
    • shares feature of protruding ears and X-linked MR as well as behaviors that are sometimes described by people as "autistic like"
  • ATR-X syndrome (X-linked alpha thalassemia, mental retardation)
    • have severe MR, congenital hypotonia, genital abmormalities and a small head
    • differs from FG because those with FG have macrocephaly, friendly personality and hyperactivity
  • Williams syndrome
    • shares personality and behavioral features with FG
    • different in that there is presence of "salient anxiety and internalizing symptoms in WS"
  • G/BBB syndrome (Opitz syndrome)
    • Considerable overlap in features of G/BBB and FG syndromes
    • Features that are shared with FG include: sensorineural dysfunction, behavioral problems, imperforate anus, hypoplasia or agenesis of the corpus callosum, kidney abnormalities, cryptorchidism, heart (cardiac) defects, and mental retardation.
    • One form of G/BBB syndrome is inherited in X-linked recessive fashion and is due to mutations in MID1 gene
    • Other symptoms of G/BBB include; dysphagia, cleft palate and or cleft lip (which are not usually seen in FG). Pulmonary agenesis or hypoplasia and tetralogy of Fallot have been seen only in the G/BBB syndrome so far.

References

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  • John Opitz, Antonio Richieri-da Costa, Jon M. Asse, and Paul J. Benke. FG Syndrome Update 1988: Note of 5 New Patients and Bibliography. American Journal of Medical Genetics. 30:309-328 (1988).
  • S Ozonoff et al. Behavior Phenotype of FG syndrome: Cognition, Personality, and Behavior in Eleven Affected Boys. American Journal of Medical Genetics 97:112-118 (2000).
  • S Briault, et al. Mapping of X Chromosome Inversion Breakpoints Associated with FG Syndrome. American Journal of Medical Genetics. 95:178-181 (2000).
  • A Lossi, A Fatima, S Briault, C Moraine, C Schwartz Exclusion of Nine Candidate Genes for Their Involvement in X-linked FG Syndrome (FGS1) in Three Families. Letter to the Editor. American Journal of Medical Genetics 94:386-388. (2000).
  • JM Grahm Jr. Clinical and Behavioral Characteristics in FG Syndrome. American Journal of Medical Genetics. 85:470-475 (1999).
  • S Briault et al. A Gene for FG Syndrome Maps in the Sq12-q21.31 Region. American Journal of Medical Genetics. 73:87-90 (1997).

Web info

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Notes

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The information in this outline was last updated in 2002.

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