DO: 14711;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq28 | ?FG syndrome 2 | 300321 | X-linked | 3 | FLNA | 300017 |
A number sign (#) is used with this entry because FG syndrome-2 (FGS2) is caused by mutation in the gene encoding filamin A (FLNA; 300017) on chromosome Xq28.
Although the phenotypic spectrum and severity of FG syndrome is wide, the cardinal features include congenital hypotonia, delayed speech development, relative macrocephaly, dysmorphic facies, and anal anomalies or severe constipation (Unger et al., 2007).
For a general phenotypic description and a discussion of genetic heterogeneity of FG syndrome, see FGS1 (305450).
Briault et al. (1999) reported a French boy with FG syndrome. His maternal uncle was mentally retarded. The proband had mental retardation, facial anomalies, prominent forehead, hypotonia, failure to thrive, constipation, and anteriorly placed anus, while his maternal uncle had mental retardation, facial anomalies, constipation, and bronchopulmonary infections, but no macrocephaly, frontal bossing, or anal anomalies.
Unger et al. (2007) reported an 18-month-old German boy with severe constipation, large rounded forehead, prominent ears, frontal hair upsweep, and mild delay in language acquisition. The parents declined brain MRI studies.
In a French boy with FG syndrome and in his mentally retarded maternal uncle, Briault et al. (1999) identified an X-chromosome inversion, inv(X)(q12q28). Using FISH in further studies of this family, Briault et al. (2000) identified 2 clones that crossed the breakpoints, one located at Xq11.2 and the other at Xq28 (FGS2).
In a German boy with FGS2, Unger et al. (2007) identified a hemizygous mutation in the FLNA gene (P1291L; 300017.0028). His asymptomatic mother also carried the mutation, which was absent in 100 control chromosomes. Unger et al. (2007) also suggested that a patient reported by Hehr et al. (2006) with a FLNA mutation (300017.0024) and periventricular heterotopia, facial dysmorphism, and constipation may have also had FGS2.
Briault, S., Odent, S., Lucas, J., Le Merrer, M., Turleau, C., Munnich, A., Moraine, C. Paracentric inversion of the X chromosome [inv(X)(q12q28)] in familial FG syndrome. Am. J. Med. Genet. 86: 112-114, 1999. [PubMed: 10449643] [Full Text: https://doi.org/10.1002/(sici)1096-8628(19990910)86:2<112::aid-ajmg4>3.0.co;2-3]
Briault, S., Villard, L., Rogner, U., Coy, J., Odent, S., Lucas, J., Passage, E., Zhu, D., Shrimpton, A., Pembrey, M., Till, M., Guichet, A., Dessay, S., Fontes, M., Poustka, A., Moraine, C. Mapping of X chromosome inversion breakpoints [inv(X)(q11q28)] associated with FG syndrome: a second FG locus [FGS2]? Am. J. Med. Genet. 95: 178-181, 2000. [PubMed: 11078572] [Full Text: https://doi.org/10.1002/1096-8628(20001113)95:2<178::aid-ajmg17>3.0.co;2-v]
Hehr, U., Hehr, A., Uyanik, G., Phelan, E., Winkler, J., Reardon, W. A filamin A splice mutation resulting in a syndrome of facial dysmorphism, periventricular nodular heterotopia, and severe constipation reminiscent of cerebro-fronto-facial syndrome. (Letter) J. Med. Genet. 43: 541-544, 2006. [PubMed: 16299064] [Full Text: https://doi.org/10.1136/jmg.2005.038505]
Unger, S., Mainberger, A., Spitz, C., Bahr, A., Zeschnigk, C., Zabel, B., Superti-Furga, A., Morris-Rosendahl, D. J. Filamin A mutation is one cause of FG syndrome. Am. J. Med. Genet. 143A: 1876-1879, 2007. [PubMed: 17632775] [Full Text: https://doi.org/10.1002/ajmg.a.31751]