Endocrine Abstracts

Introduction: The Dandy-Walker complex (DW) comprises a rare intracranial malformation of the posterior fossa and multiple organ anomalies. The association with endocrine pathology is rare - described in isolated cases (Kallman syndrome, primary hypothyroidism (PH) and central precocious puberty). Noonan syndrome (NS) is a genetic disease usually diagnosed at birth, with variable phenotype. Most cases have AD transmission, with the PTPN11 gene mutation responsible for 50%.

Case report: Male patient referred for consultation at 16 years due to short stature and delayed puberty. At 1st evaluation: height 148.5cm (-3.1 SD), weight 41 Kg, pubertal stage P3, testicular volume 10mL; facial dimorphisms (hypertelorism, bulbous nose, triangular face), and 5th finger’s brachydactyly. Past medical history of congenital diaphragmatic hernia, intestinal occlusion at 11 months, strabismus, delayed developmental milestones and unilateral cryptorchidism (surgically corrected at 12y). Family target height of 165 cm. He denied olfactory dysfunction. Of the complementary diagnostic exams: bone age of 13y1month; FSH <0.3 mIU/ml; LH <0.1 mIU/ml; total and free testosterone (TT/FT) 2.2 ng/ml (2,7-11) and 3.3 pg/ml (13-40); LHRH stimulation test with FSH 15.7 mIU/ml and LH 14.5 mIU/ml post stimulation; primary hypothyroidism (TSH 5.7 uIU/ml; T4L 0.7 ng/dl – started LT4 25 mg); 46XY karyotype; brain MRI showed “patency of the olfactory bulbs, identifying both olfactory sulci, without hypothalamic-pituitary alterations; increase in fourth ventricle dimensions, focal increase in retrocerebellar extra-axial space - DW variant”. Genetic study (CGH-array) without alterations. He started induction of puberty with testosterone enanthate 125 mg monthly, until 20y, with a final height of 162.1 cm (-2 SD), P5 Tanner stage, and testicular volume of 25mL. Lost of follow up until 30y. At 30y: FSH 11 mUI/ml, LH 4.5 mUI/ml, and TT 5,3 ng/ml; new genetic study by total exomic sequencing, with identification of the variant c.1472C>T p.(Pro491Leu), in heterozygosity, in the PTPN11 gene, classified as pathogenic – Noonan Syndrome type 1.

Conclusion: This case illustrates the rare association of a patient with NS, DW variant and delayed puberty. The diagnosis of NS only at adulthood shows how genetic testing has improved over the years. The DW variant explains diaphragmatic hernia, intestinal obstruction, hypertelorism, and eventually the PH. NS explains facial dimorphism, cryptorchidism and learning difficulties, as well as short stature and delayed puberty. Diagnosis of NS is of particular importance for surveillance of comorbidities and genetic counseling.