ORPHA: 648; DO: 0060585;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 7q34 | Noonan syndrome 7 | 613706 | Autosomal dominant | 3 | BRAF | 164757 |
A number sign (#) is used with this entry because this form of Noonan syndrome (NS7) is caused by heterozygous mutation in the BRAF gene (164757).
Cardiofaciocutaneous syndrome (CFCS; 115150) and LEOPARD syndrome-3 (613707) can also be caused by mutation in the BRAF gene, indicating that they are allelic disorders.
For a general phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950).
Noonan syndrome is a developmental disorder characterized by reduced postnatal growth, dysmorphic facial features, cardiac defects, and variable cognitive defects (summary by Sarkozy et al., 2009).
Sarkozy et al. (2009) reported 5 unrelated patients with Noonan syndrome-7. Common clinical features included poor neonatal growth, variable feeding difficulties, short stature, mild to moderate cognitive defects, skeletal anomalies, and hypotonia. Dysmorphic facial features included dolichocephaly, prominent forehead, hypertelorism, and low-set ears with thickened helices. Two patients had congenital cardiac defects, pulmonary stenosis and atrial septal defect, respectively, and 3 had hyperpigmented cutaneous lesions.
In 5 (1.9%) of 270 patients with a clinical diagnosis of Noonan syndrome, Sarkozy et al. (2009) identified 4 different heterozygous de novo mutations in the BRAF gene (164757.0022, 164757.0023, 164757.0025, and 164757.0026).
Sarkozy, A., Carta, C., Moretti, S., Zampino, G., Digilio, M. C., Pantaleoni, F., Scioletti, A. P., Esposito, G., Cordeddu, V., Lepri, F., Petrangeli, V., Dentici, M. L., and 15 others. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Hum. Mutat. 30: 695-702, 2009. [PubMed: 19206169] [Full Text: https://doi.org/10.1002/humu.20955]