FG syndrome update 1988: note of 5 new patients and bibliography.

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.