Endocrine Abstracts

Background: Noonan syndrome (NS) is a relatively common disease, clinically and genetically heterogeneous. It is characterized by facial dysmorphia, growth retardation, congenital heart disease, lymphatic dysplasia, among others. The diagnosis is clinical, according to van der Burgt criteria. In 61% of cases genetic mutations in the signaling pathway of RAS-MAPK are identified.

Clinical case: BVM, male, NS suspected. At 3 years old sent to Pediatric Endocrinology for macrogenitossomy. Personal history: polyhydramnios at 22 weeks of pregnancy, amniocentesis: karyotype 46XY; term birth, weight 4090 g (1.36 SDS), length 50 cm (0.09 SDS), Apgar score 9/10 and congenital heart disease (hypertrophic cardiomyopathy and pulmonary stenosis). Heart disease corrected at 2 years by pulmonary valvuloplasty. Family history: irrelevant. Physical examination (PE): weight 17.6 kg (0.62 SDS), height 103.2 cm (1.05 SDS), growth velocity (GV) 8.2 cm/year (0.1 SDS); dolichocephaly, ptosis, hypertelorism, antimongoloidal palpebral fissures, low-set ears and hair, extended filtrum, high-arched palate, short and broad neck, pterygium colli, shield chest and cubitus valgus, edema of lower limbs, scrotum and penis, without Godet’s sign, Tanner: P1G1. Evaluation: target height 1.71 cm (−0.82 SDS). Bone age: 3 years. Laboratory: TSH 1.44 mIU/ml (RR: 0.35–5.50), IGF1 90 ng/ml (RR: 50–237), IGFBP3 4 μg/ml (RR: 0.2–6.6). Diagnosis of lymphedema. Referred to physical rehabilitation department for medical lymphatic drainage. At 15 years he returned to Endocrinology for delayed puberty. Presented progressive growth delay since 8 years, several hospitalizations for cellulitis and lymphangitis of lower limbs and genitals, and chylothorax. PE: weight 47.3 kg (−1.45 SDS), height 157.2 cm (−1.94 SDS), GV 3.5 cm/year (−2.10 SDS), lymphedema of lower limbs, scrotum and penis, Tanner P1G1. Bone age: 13 years. Laboratory: IGF1 70 ng/ml (RR: 143–996), IGFBP3 3.2 μg/ml (RR: 1.3–10), testosterone 0.1 ng/ml (RR: 3.5–13.5); LHRH test: FSH peak 11.3 IU/l, LH peak 7.1 IU/l. Testosterone therapy was initiated. Molecular study of PTPN11, SOS1, RAF1 and KRAS1 genes was negative; awaits further genetic study.

Conclusions: The case described points to clinical suspicion of Noonan syndrome and the need for regular endocrine evaluation. The GH–IGF1 and gonadal axis are the most affected. Early detection and treatment of endocrine abnormalities contributes to life quality improvement of these patients.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.