ESPE Abstracts

Background: Neurofibromatosis-Noonan Syndrome (NFNS) is a distinct entity which has variable features of both neurofibromatosis 1 (NF1) and Noonan syndrome (NS). In majority of cases NF1 mutations have been demonstrated. Short stature is one of the major causes for these patients requiring medical attention. GH deficiency (GHD) may accompany in some cases with NF1 or NS cases, however there are rare case reports on NFNS receiving GH therapy.

Objective and hypotheses: We hypothesized that GHD may accompany NFNS and the patients with NFNS should be evaluated for GHD.

Method: A case with NFNS having NF1 gene defect and fulfilling the criteria of GHD is presented.

Results: A 13-year-old girl presented with short stature. Physical examination revealed multiple café-au-lait spots, axillary freckling, relative macrocephaly suggesting NF1, and dysmorphic facial features, short and webbed neck, low posterior hairline, cubitus valgus, brachy and clinodactly, widely spaced nipples suggesting NS. Her height SDS was −4.4 and height velocity SDS −3.4. Puberty was at Tanner stage 3. Karyotype analysis was 46,XX. Her father also had features of both NF1 and NS. The genetic analysis of the patient and the father both revealed a truncating mutation in the NF1 gene c.7846C>T(M82814), p.Arg2616X (AAA59924). Peak GH response was 3.9 ng/ml in stimulation tests; IGF1 and IGFBP3 SDS levels <−3. She had neither hypothyroidism nor adrenal insufficiency. MRI of cranium showed lesions of NF in cerebral peduncles and globus pallidus, and pituitary gland was hypoplasic. Since the patient fulfilled the criteria of GHD, GH treatment was started. Height velocity during the first year of GH treatment was 8 cm/year.

Conclusion: Short stature is a feature of NFNS, however in some cases it can be caused by GHD. GH therapy may be beneficial in patients with NFNS who are diagnosed as GHD.