Alternative titles; symbols
SNOMEDCT: 109409003; ICD10CM: Q75.03; ORPHA: 3366;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 8p11.23 | Trigonocephaly 1 | 190440 | Autosomal dominant | 3 | FGFR1 | 136350 |
A number sign (#) is used with this entry because of evidence that trigonocephaly-1 (TRIGNO1) is caused by heterozygous mutation in the FGFR1 gene (136350) on chromosome 8p11.
Individuals with trigonocephaly have a keel-shaped forehead with wide biparietal diameter, resulting in a triangular shape of the head. Trigonocephaly results from premature closure of the metopic sutures and usually occurs sporadically (summary by Frydman et al., 1984).
Genetic Heterogeneity of Isolated Trigonocephaly
Also see trigonocephaly-2 (TRIGNO2; 614485), caused by mutation in the FREM1 gene (608944) on chromosome 9p22.
Frydman et al. (1984) described trigonocephaly unassociated with functional brain abnormalities as a distinct autosomal dominant entity. The craniosynostosis was limited to the metopic region, giving a prow appearance to the forehead. Male-to-male transmission was noted. The trait was observed in 6 persons in 4 sibships of 3 generations and by implication in another, the original progenitor, who had affected descendants by each of 2 wives. The propositus was ascertained bt birth because of omphalocele. In addition to trigonocephaly, he had minor ear, vertebral, and genital abnormalities. His father had mild microcephaly and both had minor eye abnormalities. None of the other 4 affected individuals had any other malformations. Frydman et al. (1984) stated that it was unclear whether the malformations in the propositus were due to clinical variability of a syndrome or merely reflected an ascertainment bias.
Hennekam and Van den Boogaard (1990) described trigonocephaly due to craniosynostosis of the metopic suture in 2 brothers. The father and paternal grandfather were also affected, and a paternal aunt may have been affected.
Jehee et al. (2005) studied 36 patients with syndromic and 40 patients with nonsyndromic trigonocephaly. In the nonsyndromic patients, the male-to-female ratio was 1.8:1 and 4 patients (10%) had familial recurrence of the disorder with consanguinity present in 1 family. Microdeletion screening at 9p24-p22 and 11q23-q24 was carried out in all patients; no deletions were found in nonsyndromic patients.
The transmission pattern of trigonocephly in a patient reported by Kress et al. (2000) was consistent with autosomal dominant inheritance.
Kress et al. (2000) screened 10 patients with nonsyndromic trigonocephaly for mutations in exon 5 of FGFR1 gene, exons 8 and 10 of the FGFR2 gene (176943), exon 7 of the FGFR3 gene (134934), and exon 1 of the TWIST1 (601622) gene (all regions known to be involved in autosomal dominant craniosynostosis syndromes). They identified 1 patient with a heterozygous ile300-to-thr (I300T) mutation in the FGFR1 gene (136350.0011).
Frydman, M., Kauschansky, A., Elian, E. Trigonocephaly: a new familial syndrome. Am. J. Med. Genet. 18: 55-59, 1984. [PubMed: 6741996] [Full Text: https://doi.org/10.1002/ajmg.1320180109]
Hennekam, R. C. M., Van den Boogaard, M.-J. Autosomal dominant craniosynostosis of the sutura metopica. Clin. Genet. 38: 374-377, 1990. [PubMed: 2282717] [Full Text: https://doi.org/10.1111/j.1399-0004.1990.tb03598.x]
Jehee, F. S., Johnson, D., Alonso, L. G., Cavalcanti, D. P., de Sa Moreira, E., Alberto, F. L., Kok, F., Kim, C., Wall, S. A., Jabs, E. W., Boyadjiev, S. A., Wilkie, A. O. M., Passos-Bueno, M. R. Molecular screening for microdeletions at 9p22-p24 and 11q23-q24 in a large cohort of patients with trigonocephaly. Clin. Genet. 67: 503-510, 2005. [PubMed: 15857417] [Full Text: https://doi.org/10.1111/j.1399-0004.2005.00438.x]
Kress, W., Petersen, B., Collmann, H., Grimm, T. An unusual FGFR1 mutation (fibroblast growth factor receptor 1 mutation) in a girl with non-syndromic trigonocephaly. Cytogenet. Cell Genet. 91: 138-140, 2000. [PubMed: 11173846] [Full Text: https://doi.org/10.1159/000056834]