Genetic testing for lymphedema in RASopathies

Open access

Abstract

Variants affecting the function of genes in the RAS–mitogen-activated protein kinase (MAPK) signal transduction pathway have been identified as responsible for a group of developmental syndromes known as RASopathies. Noonan (NS) and cardiofaciocutaneous syndromes (CFC) represent the most frequent and best characterized RASopathies. Many cases of RASopathies are associated with lymphatic malformations that finally may result in lymphedema. We developed the test protocol “Lymphedema in RASopathies” on the basis of the latest research findings and diagnostic protocols on lymphatic malformation in RASopathies. The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

1. Rauen KA. The RASopathies. Annu Rev Genomics Hum Genet 2013; 14: 355-69.

2. Kaplan MS, Optiz JM, Cosset FR. Noonan’s syndrome: A case with elevated serum alkaline phosphatase levels and malignant schwannoma of the left forearm. Am J Dis Child 1968; 116(4): 359-66.

3. Wyre HW Jr. Cutaneous manifestations of Noonan’s syndrome. Arch Dermatol 1978; 114(6): 929-30.

4. Allanson JE. Noonan syndrome. J Med Genet 1987;24(1):9-13.

5. Sharland M, Burch M, McKenna WM, Patton MA. A clinical study of Noonan syndrome. Arch Dis Child 1992; 67(2):178-183.

6. Smpokou P, Tworog-Dube E, Kucherlapati RS, Roberts AE. Medical complications, clinical findings and educational outcomes in adults with Noonan syndrome. Am J Med Genet A 2012; 158A(12): 3106-3111.

7. Joyce S, Gordon K, Brice G, Ostergaard P, Nagaraja R, Short J, Moore S, Mortimer P, Mansour S. The lymphatic phenotype in Noonan and Cardiofaciocutaneous syndrome. Eur J Hum Genet. 2016; 24(5): 690-6.

8. Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, Hählen K, Hasle H, Licht JD, Gelb BD. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 2003; 34(2): 148-50.

9. Stark M, Assum G, Krone W. A small deletion and an adjacent base exchange in a potential stem-loop region of the neurofibromatosis 1 gene. Hum Genet 1991; 87(6): 685-87.

10. Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet 2002; 70(6): 1555-63.

11. Rauen KA. Cardiofaciocutaneous syndrome. In: RA Pagon, MP Adam, HH Ardinger, SE Wallace, A Amemiya, LJH Bean, et al., editors. GeneReviews. 2016. Seattle (WA).

12. Brouillard P, Boon L, Vikkula M. Genetics of lymphatic anomalies. J Clin Invest 2014; 124(3): 898-904.

13. Allanson JE, Roberts AE. Noonan Syndrome. In: RA Pagon, MP Adam, HH Ardinger, SE Wallace, A Amemiya, LJH Bean, et al., editors. GeneReviews. 2001. Seattle (WA).

Journal Information

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 55 55 12
PDF Downloads 19 19 2