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Multiple café au lait spots in familial patients with MAP2K2 mutation.
Am J Med Genet A. 2014 Feb; 164A(2):392-6.AJ

Abstract

Recent advances in genetic diagnostic technologies have made the classic disease nosology highly complicated. This situation is exemplified by rasopathies, among which neurofibromatosis type 1 and Noonan syndrome represent prototypic entities. The former condition is characterized by multiple café au lait spots and neurofibromas, while the latter is characterized by distinct facial features, webbed neck, congenital heart disease, and a short stature. On rare occasions, the features of both neurofibromatosis and Noonan syndrome co-exist within an individual; such patients are diagnosed as having neurofibromatosis-Noonan syndrome. Here, we report familial patients with multiple café au lait spots and Noonan syndrome-like facial features. A mutation analysis unexpectedly revealed a mutation in MAP2K2 in both the propositus and his mother. The propositus fulfilled the diagnostic criteria for neurofibromatosis type 1, but his mother did not. Their phenotype was not consistent with that of cardio-facio-cutaneous syndrome, which is classically known to be associated with MAP2K2 mutations. The mother of the propositus had cervical cancer at the age of 23 years, consistent with the oncogenic tendency associated with rasopathies. The phenotypic combination of multiple café au lait spots and Noonan syndrome-like facial features suggested a diagnosis of neurofibromatosis-Noonan syndrome. Whether this condition represents a discrete disease entity or a variable expression of neurofibromatosis type 1 has long been debated. The present observation suggests that some perturbation in the RAS/MAPK signaling cascade results in multiple café au lait spots, a key diagnostic phenotype of rasopathies, although the exact mechanism remains to be elucidated.

Authors+Show Affiliations

Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

24311457

Citation

Takenouchi, Toshiki, et al. "Multiple Café Au Lait Spots in Familial Patients With MAP2K2 Mutation." American Journal of Medical Genetics. Part A, vol. 164A, no. 2, 2014, pp. 392-6.
Takenouchi T, Shimizu A, Torii C, et al. Multiple café au lait spots in familial patients with MAP2K2 mutation. Am J Med Genet A. 2014;164A(2):392-6.
Takenouchi, T., Shimizu, A., Torii, C., Kosaki, R., Takahashi, T., Saya, H., & Kosaki, K. (2014). Multiple café au lait spots in familial patients with MAP2K2 mutation. American Journal of Medical Genetics. Part A, 164A(2), 392-6. https://doi.org/10.1002/ajmg.a.36288
Takenouchi T, et al. Multiple Café Au Lait Spots in Familial Patients With MAP2K2 Mutation. Am J Med Genet A. 2014;164A(2):392-6. PubMed PMID: 24311457.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple café au lait spots in familial patients with MAP2K2 mutation. AU - Takenouchi,Toshiki, AU - Shimizu,Atsushi, AU - Torii,Chiharu, AU - Kosaki,Rika, AU - Takahashi,Takao, AU - Saya,Hideyuki, AU - Kosaki,Kenjiro, Y1 - 2013/12/05/ PY - 2013/05/20/received PY - 2013/09/13/accepted PY - 2013/12/7/entrez PY - 2013/12/7/pubmed PY - 2014/9/12/medline KW - MAP2K2 KW - Noonan syndrome KW - cafe au lait spots KW - neurofibromatosis type 1 KW - neurofibromatosis-Noonan syndrome KW - rasopathies SP - 392 EP - 6 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 164A IS - 2 N2 - Recent advances in genetic diagnostic technologies have made the classic disease nosology highly complicated. This situation is exemplified by rasopathies, among which neurofibromatosis type 1 and Noonan syndrome represent prototypic entities. The former condition is characterized by multiple café au lait spots and neurofibromas, while the latter is characterized by distinct facial features, webbed neck, congenital heart disease, and a short stature. On rare occasions, the features of both neurofibromatosis and Noonan syndrome co-exist within an individual; such patients are diagnosed as having neurofibromatosis-Noonan syndrome. Here, we report familial patients with multiple café au lait spots and Noonan syndrome-like facial features. A mutation analysis unexpectedly revealed a mutation in MAP2K2 in both the propositus and his mother. The propositus fulfilled the diagnostic criteria for neurofibromatosis type 1, but his mother did not. Their phenotype was not consistent with that of cardio-facio-cutaneous syndrome, which is classically known to be associated with MAP2K2 mutations. The mother of the propositus had cervical cancer at the age of 23 years, consistent with the oncogenic tendency associated with rasopathies. The phenotypic combination of multiple café au lait spots and Noonan syndrome-like facial features suggested a diagnosis of neurofibromatosis-Noonan syndrome. Whether this condition represents a discrete disease entity or a variable expression of neurofibromatosis type 1 has long been debated. The present observation suggests that some perturbation in the RAS/MAPK signaling cascade results in multiple café au lait spots, a key diagnostic phenotype of rasopathies, although the exact mechanism remains to be elucidated. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/24311457/Multiple_café_au_lait_spots_in_familial_patients_with_MAP2K2_mutation_ L2 - https://doi.org/10.1002/ajmg.a.36288 DB - PRIME DP - Unbound Medicine ER -