FG syndrome update 1988: Note of 5 new patients and bibliography

Abstract

At the eve of its mapping, the pre-molecular picture of the FG syndrome is heavily biased towards the severe end of the phenotypic spectrum because present knowledge is largely based on propositi. It is an X-linked, incompletely recessive, complexly pleiotropic syndrome with considerably variable expressivity. Though a true multiple congenital anomalies/mental retardation (MCA/MR) syndrome, severe malformations are uncommon and involve mostly the anus (60%) and non-colonic GI defects (33%), hypospadias (25%), cleft palate (6%), rarely a congenital heart defect. The complex CNS dysfunctions of congenital hypotonia and all of its sequelae, MR, and occasional seizures, must be attributed to a developmental CNS defect which is rarely demonstrated at pre-mortem, and which is known to involve agenesis of the corpus callosum in some 25% of appropriately studied patients (mostly propositi). Thus, the diagnosis is largely made on a specific constellation of minor anomalies and mild malformations in a hypotonic boy with severe constipation and a very characteristic facial appearance and behavioral phenotype. In about 1/3 of cases, carrier manifestations may be detected physically. New hemizygote manifestations seen in this review of 5 new patients include abnormal eruption of teeth, diastasis between upper central incisors, apparent gynecomastia, cleft lip, and nasolacrimal and helicine fistulae. Only a half hundred or so FG syndrome patients are known, but we suspect the syndrome is much more common than realized, and because of the unfortunate recurrence risk potential, deserves careful consideration in every appropriate case. RFLP mapping studies are urged in order to aid diagnosis of "mild" cases, and prenatal and carrier detection.

Paracentric inversion of the X chromosome [inv(X)(q12q28)] in familial FG syndrome

“…FG syndrome (MIM 305450) is a rare X-linked incomplete recessive condition comprising congenital hypotonia, mental retardation, macrocephaly, constipation and/or anal anomalies, and such facial anomalies as prominent forehead, frontal hair upsweep, and hypertelorism [Opitz et al, 1988]. Linkage analyses in 10 families [Briault et al, 1997] demonstrated heterogeneity and assigned one gene (FGS1) to chromosome region Xq12-q21.31.…”

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

“…One example is FG syndrome, which has a gene map locus of Xq12-q21.31. Patients with FG syndrome are affected with mental retardation, disproportionately large head, hypospadia, cleft lip/palate, cogenital hypotonia, and ACC (Opitz et al, 1988;Dessay et al, 2002). Interestingly, ephrinB1 is localized to this same locus (Xq12-q13.1), although it is unclear whether ephrinB1 is responsible for the ACC phenotype.…”

Esophageal dysmotility in brothers with an FG-like syndrome

“…Over 50 boys with the syndrome have been reported, and up to one-third of obligate carrier females have some of the facial features [Keller et al, 1976;Opitz et al, 1988;Thompson et al, 1985].…”

“…The phenotype is better known and includes boys with less severe manifestations [Opitz et al, 1988]. There was suggestion of phenotypic overlap with the fragile X syndrome [Loesch et al, 1992;Puissan et al, 1996].…”

“…Symptoms of gastro-esophageal reflux (GER) are strikingly common, are associated with severe failure to thrive in infancy, and are often manifested by prolonged screaming attacks and unsettled feeding behavior. Esophageal stenosis secondary to reflux was described Opitz et al [1988] in a boy with FG syndrome and severe gastrointestinal disease with multiple small intestinal atresias. Noncolonic gastrointestinal manifestations, such as pyloric stenosis and atresias, occur in up to 30% of boys with FG syndrome in some series [Opitz et al, 1988;Thompson and Baraitser, 1987].…”