Studies of malformation syndromes of man XXXIII: The FG syndrome. An X-linked recessive syndrome of multiple congenital anomalies and mental retardation

Abstract

Abstract. Three brothers and two of their male first cousins were affected with a previously apparently undefined multiple congenital anomaly, mental retardation syndrome which was designated the FG syndrome and which consists of variable growth problems with a disproportionately large head, characteristic appearance and minor anomalies, imperforate anus, mild to severe mental retardation and congenital hypotonia; pylorie stenosis, hypoplastic left heart, generalized dilatation of the urinary tract, cutaneous syndaetyly of third and fourth fingers, and severe craniosynostosis were seen each in i patient. Partial agenesis of the corpus callosum seen in 1 patient is suspected in another on the basis of EEG abnormalities. 1 boy died neonatally with congenital heart disease, and 2 others of pneumonia at 20 and 23 months. The FG syndrome is an X-linked recessive condition; heterozygotes appear grossly normal.Key words: Multiple congenital anomaly/mental retardation (MCA/MR) syndrome --Growth disturbances --Increased headsize --Hypotonia --Imperforate anus --Partial agenesis of corpus callosum --Pyloric stenosis --Generalized dilatation of urinary tract --Hypoplastie left heart defect --Syndactyly of toes and/or fingers --Craniosynostosis --X-linked inheritance. This paper reports on 5 related boys with an apparently previously undeseribed X-linked multiple congenital anomaly/mental retardation (MCA/MR) syndrome of external anomalies, characteristic appearance, visceral anomalies, skeletal defects and CNS anomaly with MR, hypotonia and unusual pattern of head growth. @ase ReportsCase l (J.J.F., propositus 1, V-5 in pedigree, Fig. 1, CWC 5-308, UW ~-Iosp. No. 370805) was born on 12 February 1959 when his parents were 27 years old. This was his mother's fifth pregnancy during which she gained 8.2 kg; she was healthy except for an upper respiratory infection and chronic cough during the 8th month. Labor began spontaneously at 37 89 weeks, and after an uneventful 3--4-hour labor, the patient, a male, was born spontaneously from a cephalic presentation with an imperforate anus, webbing of the third and fourth fingers bilaterally and a "protruberant xiphoid'. His birth weight was 2600 g, occipito-frontal head circumference (O•C) 34.3 cm, chest circumference 28 cm, and the anterior fontanel measured "3 fingers". He was otherwise thought to be normal. A primary pullthrough operation was performed on the day of birth; at surgery it was found that he had a relatively low rectal atresia with a small tract or fibrous band extending from the anterior-distal portion of the rectum to the region of the urethra. The external sphincter fibers were identified, there was adequate bowel length, and after opening the bowel much normal meconium could be evacuated before the rectal mueosa was sutured to the anus. The wound healed normally and at the iOth day dilatation of the anus was begun with some prolapse of mucosa.Postoperatively he fed rather poorly and examination showed that he had a ruddy-icteric color, a somewhat hoarse and squeaky...

Med12 is essential for early mouse development and for canonical Wnt and Wnt/PCP signaling

“…The Opitz-Kaveggia and Lujan syndromes have overlapping (mental retardation, macrocephaly) and also specific (imperforate anus in Opitz-Kaveggia, craniofacial abnormalities in Lujan) manifestations (Opitz and Kaveggia, 1974;Risheg et al, 2007;Schwartz et al, 2007). These symptoms also implicate Med12 as a subunit with gene-specific functions within the Mediator.…”

MED12 mutations in human diseases

“…In 2007, Risheg found that there are frequent mutations in the twenty-fi rst exon of MED12 of FG syndrome patients, which results in C2881T and R961W mutations in the protein. Thereafter, the relationship between FG syndrome and mutations in MED12 was confi rmed by several other groups (Opitz and Kaveggia, 1974;Risheg et al, 2007;Graham et al, 2008;Graham et al, 2010). In addition, Rump P and colleagues found that three cousins suffering from FG syndrome all bear a mutation (G958E) in MED12, suggesting that the G958E mutation may also cause FG syndrome (Rump et al, 2011).…”

“…FG syndrome, also called Opitz-Kaveggia syndrome, was fi rst reported by OpitzKaveggia in 1974 (Opitz andKaveggia, 1974). It is an X chromosome-associated genetic disease.…”

Epidemiologie genetique et effet fondateur dans la polyneuropathie sensitivo-motrice avec ou sans agenesie du corps calleux au Saguenay-Lac-St-Jean

“…L'agéné^i du corps calleux, partielle ou complète, comme symptôme ou comme maladie a été mise en relation avec plusieurs modes de transmission: lié au sexe (Menkes et al, 1964;Opitz et Kaveggia, 1974), autosomal dominant (Lynn et al, 1980) et autosomal récessif (Shapira et Cohen, 1973;Ozdirim et Renda, 1978). On doit signaler le syndrome d'Aicardi (Aicardi et al, 1965) qui pourrait s'avérer multifactoriel avec une "préférence" pour les femmes (Aicardi et al, 1969;Dennis et Bower, 1972;De Jong et al, 1976).…”