Alternative titles; symbols
SNOMEDCT: 771338002; ORPHA: 251290;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q35.2 | Parietal foramina with cleidocranial dysplasia | 168550 | Autosomal dominant | 3 | MSX2 | 123101 |
A number sign (#) is used with this entry because of evidence that parietal foramina with cleidocranial dysplasia is caused by heterozygous mutation in the MSX2 gene (123101) on chromosome 5q35.
See 119600 for a discussion of cleidocranial dysplasia and 168500 for a discussion of parietal foramina.
Eckstein and Hoare (1963) reported mother and son with parietal foramina and clavicular hypoplasia. Golabi et al. (1983) reported a second family with 3 generations affected including male-to-male transmission.
Garcia-Minaur et al. (2003) described a 3-generation family segregating parietal foramina with cleidocranial dysplasia. Affected family members exhibited classic parietal foramina and short abnormal clavicles with tapering lateral ends. They had mild craniofacial dysmorphism with a broad forehead and central bossing, which was more evident in the children.
The transmission pattern of PFMCCD in the families reported by Golabi et al. (1983) and Garcia-Minaur et al. (2003) was consistent with autosomal dominant inheritance.
In a 3-generation family segregating parietal foramina with cleidocranial dysplasia, Garcia-Minaur et al. (2003) identified heterozygosity for a frameshift mutation in the homeodomain of the MSX2 gene predicting a termination codon 75 triplets downstream (123101.0007). The authors concluded that PFMCCD is etiologically distinct from classic cleidocranial dysplasia, which is caused by mutations in the RUNX2 gene (600211), and is allelic to PFM1 (see 168500), in which MSX2 mutations had previously been identified. Garcia-Minaur et al. (2003) also noted that the clavicular involvement was mild and difficult to assess on physical examination, and suggested that this finding may be more commonly associated with PFM than previously believed and may be characteristic of affected individuals with MSX2 rather than ALX4 (605420) mutations.
Eckstein, H. B., Hoare, R. D. Congenital parietal 'foramina' associated with faulty ossification of the clavicles. Brit. J. Radiol. 36: 220-221, 1963.
Garcia-Minaur, S., Mavrogiannis, L. A., Rannan-Eliya, S. V., Hendry, M. A., Liston, W. A., Porteous, M. E. M., Wilkie, A. O. M. Parietal foramina with cleidocranial dysplasia is caused by mutation in MSX2. Europ. J. Hum. Genet. 11: 892-895, 2003. [PubMed: 14571277] [Full Text: https://doi.org/10.1038/sj.ejhg.5201062]
Golabi, M., Carey, J., Hall, B. Parietal foramina-cleidocranial dysplasia: an autosomal dominant syndrome--report of second affected family. (Abstract) Proc. Greenwood Genet. Center 2: 116 only, 1983.