Genetic counseling: FG Syndrome

FG Syndrome

Introduction and Contracting

 * 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

 * 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

 * 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

 * 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

 * 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 impulsivness 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

 * 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

 * 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

 * 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

 * 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

 * 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.

Web info

 * 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.geocities.com/HotSprings/Spa/3687/ (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.