Handbook of Genetic Counseling/FG Syndrome
Introduction and Contracting Edit
- 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
- 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 Edit
- 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 Edit
- 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 Edit
- 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 Edit
- 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"
- 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)
- 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 Edit
- 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 Edit
- 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.
- 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 Edit
- http://www.gle.egsd.k12.co.us/opitz/opitznord.html -- (information about Opitz G/BBB syndrome)
- Opitz JM, FG syndrome. Orphanet encyclopedia, September 2001: http://orphanet.infobiogen.fr/data/patho/GB/uk-FG.html
- http://www.fg-syndrome.org (FG Syndrome Family Alliance web site)
- This site seems to be biased towards the opinions of Dr. Opitz which are not shared by all medical professionals.
The information in this outline was last updated in 2002.