Neuropediatrics 2016; 47 - P07-05
DOI: 10.1055/s-0036-1583684

Neurofibromatosis-Noonan Syndrome Due to a Newly Occurred Microdeletion 17q11.2

N. Kienle 1, K. Marquard 1, M. Blankenburg 1, C. Spaich 2, E. Fiedler 2
  • 1Pädiatrische Neurologie, Psychosomatik und Schmerztherapie, Kinderschmerzzentrum Baden-Württemberg, Zentrum für Kinder- und Jugendmedizin Olgahospital, Klinikum Stuttgart, Deutschland
  • 2Institut für Klinische Genetik, Olgahospital und Frauenklinik, Klinikum Stuttgart, Deutschland

Background: Noonan syndrome (NS; 1: 500–2,500 births) and neurofibromatosis type 1 (NF1; 1: 3,000) are among the most common genetic diseases. They belong to the neuro-cardio-facio-cutaneous syndromes, which are accompanied by an over-function of the RAS-MAPK pathway (so-called RASopathies). RAS is involved in the induction of unhindered cell growth, disturbance of apoptosis, cell invasivity, and neoangiogenesis. We describe a boy with clinical symptoms of NF1 and NS.

Methods: In a preterm 34 + 5 of gestational age with supraventricular pulmonary stenosis a Noonan syndrome was suspected. With 5 months, there was a global development disorder, brachycephaly, broad forehead with prominent metopic suture, infraorbital folds, pointed chin, low-set ears, short neck, excess skin on the neck and > 6 café-au-lait spots with a diameter > 0.5 cm. Sonography of the skull, hips, kidney and hearing screening was normal.

Results: The array CGH showed a heterozygous microdeletion on chromosome 17q11.2 with a size of 1375Mb and a microduplication 12q13.13. In the parents, only the mother had a microduplication 12q13.13.

Conclusion: Due to repeated observation of features of NS in NF1 patients it has been discussed whether neurofibromatosis-Noonan syndrome (NFNS) is a disease entity or a special form of NF1 or NS. The deletion in the NF1 gene on chromosome 17 (17q11.2) in our patient speaks for a special form of NF1 in accordance with other studies showing mutations or deletions in the NF1 gene in most cases of NFNS patients. The genetic mechanisms of this phenotype are not yet clear.