Clinical and molecular aspects of an informative family with neurofibromatosis type 1 and Noonan phenotype

• Published in: Clinical genetics 2006-03, Vol.69 (3), p.246-253
• Main Authors: Stevenson, DA, Viskochil, DH, Rope, AF, Carey, JC
• Format: Article
• Language: English
• Subjects: Adolescent; Alleles; Biological and medical sciences; Child; Child, Preschool; Diseases of the osteoarticular system; Female; General aspects. Genetic counseling; Genes, Neurofibromatosis 1; Humans; Infant; Intracellular Signaling Peptides and Proteins - genetics; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical genetics; Medical sciences; Mutation; neurofibromatosis; Neurofibromatosis 1 - complications; Neurofibromatosis 1 - genetics; Neurology; Noonan syndrome; Noonan Syndrome - complications; Noonan Syndrome - genetics; Pedigree; Phenotype; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatases - genetics; PTPN11; pulmonic stenosis; Sequence Deletion; Tumors of the nervous system. Phacomatoses
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2006.00576.x

Neurofibromatosis–Noonan syndrome (NFNS) has been described as a unique phenotype, combining manifestations of neurofibromatosis type 1 (NF1) and Noonan syndrome, which are separate syndromes. Potential etiologies of NFNS include a discrete syndrome of distinct etiology, co‐segregation of two mutated common genes, variable clinical expressivity of NF1, and/or allelic heterogeneity. We present an informative family with an unusual NF1 mutation with variable features of NF1 and Noonan syndrome. We hypothesize that an NF1 mutant allele can lead to diagnostic manifestations of Noonan syndrome, supporting the hypothesis that NF1 allelic heterogeneity causes NFNS.