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. 2009 Nov;11(11):769-75.
doi: 10.1097/GIM.0b013e3181bd3d90.

FG syndrome, an X-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing

Robin Dawn Clark  1 , John M Graham Jr, Michael J Friez, Joe J Hoo, Kenneth Lyons Jones, Carole McKeown, John B Moeschler, F Lucy Raymond, R Curtis Rogers, Charles E Schwartz, Agatino Battaglia, Michael J Lyons, Roger E Stevenson
Affiliations

FG syndrome, an X-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing

Robin Dawn Clark et al. Genet Med. 2009 Nov.

Abstract

FG syndrome is a rare X-linked multiple congenital anomaly-cognitive impairment disorder caused by the p.R961W mutation in the MED12 gene. We identified all known patients with this mutation to delineate their clinical phenotype and devise a clinical algorithm to facilitate molecular diagnosis. We ascertained 23 males with the p.R961W mutation in MED12 from 9 previously reported FG syndrome families and 1 new family. Six patients are reviewed in detail. These 23 patients were compared with 48 MED12 mutation-negative patients, who had the clinical diagnosis of FG syndrome. Traits that best discriminated between these two groups were chosen to develop an algorithm with high sensitivity and specificity for the p.R961W MED12 mutation. FG syndrome has a recognizable dysmorphic phenotype with a high incidence of congenital anomalies. A family history of X-linked mental retardation, deceased male infants, and/or multiple fetal losses was documented in all families. The algorithm identifies the p.R961W MED12 mutation-positive group with 100% sensitivity and 90% specificity. The clinical phenotype of FG syndrome defines a recognizable pattern of X-linked multiple congenital anomalies and cognitive impairment. This algorithm can assist the clinician in selecting the patients for testing who are most likely to have the recurrent p.R961W MED12 mutation.

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Figures

Fig. 1
Fig. 1
Pedigrees of 10 families with FG syndrome (see Figures, Supplemental Digital Content 1 and 2, http://links.lww.com/GIM/A87 and http://links.lww.com/GIM/A88.). Family 1 has not been reported previously. Family 2, III-1 was included in the report of Briault et al. Family 3, IV-1 was reported by Lyons et al. Family 4, III-2, III-4, III-5, III-9, and III-10 (the original FG family) were reported first by Opitz and Kaveggia. Family 4, III-11 was first reported by Riccardi et al. as patient I-6. Family 5, II-1, II-3, and II-10 were reported by Keller et al. Family 6, III-3 was reported by McCardle and Wilson as J.B. Family 7 was reported by Graham et al. as Family 1. Family 8 was reported by Graham et al. as Family 3. Family 9 was reported by Graham et al. and by Opitz et al. as Family 3, Patient 4. Family 10 was reported by Graham et al.
Fig. 2
Fig. 2
a–d, Family 1, Patient IV-2, at age 2 years 3 months, 11 years 10 months, and 18 years.
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References

    1. Opitz JM, Kaveggia EG. Studies of malformation syndromes of man 33: the FG syndrome. An X-linked recessive syndrome of multiple congenital anomalies and mental retardation. Z Kinderheilkd. 1974;117:1–18. - PubMed
    1. Risheg H, Graham JM, Jr, Clark RD, et al. A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nat Genet. 2007;39:451–453. - PubMed
    1. Lyons MJ, Graham JM, Jr, Neri G, et al. Clinical experience in the evaluation of 30 patients with a prior diagnosis of FG syndrome. J Med Genet. 2009;46:9–13. - PubMed
    1. Keller MA, Jones KL, Nyhan WL, Francke U, Dixson B. A new syndrome of mental deficiency with craniofacial, limb and anal abnormalities. J Pediatr. 1976;88:589 –591. - PubMed
    1. Riccardi VM, Hassler E, Lubinsky MS. The FG syndrome: further characterization, report of a third family, and of a sporadic case. Am J Med Genet. 1977;1:47–58. - PubMed

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