ODP401 A new FGFR1 mutation causing Idiopathic Hypogonadotropic Hypogonadism and Polydactyly

Abstract

Abstract Introduction Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a heterogeneous condition with unknown genetic basis in approximately 30% of patients. We describe a case with normosmic IHH and an unreported FGFR1 mutation. Case Report A 23-year-old hispanic man, with a history of polydactyly presented to our clinic for evaluation of delayed puberty. He had no facial hair and minimal pubic and axillary hair. He reported fatigue, low libido and scant ejaculation. He denied anosmia, eating disorders, learning disability, urological malformations, obesity, galactorrhea, testicular trauma, mumps, or use of androgenic steroids. Family history was significant for polydactyly in his mother. Physical exam findings showed normal vitals, height 185 cm, BMI 24 kg/m2, eunuchoid body habitus, bilateral gynecomastia, no facial hair, scant axillary and pubic hair, prepubertal 2 ml testicles within the scrotum and a micro-penis. Serum total testosterone was 7 ng/dl (250-1100 ng/dl), free testosterone 0.9 pg/ml (9.3-26.5 pg/ml), FSH 2.2 mIU/ml (1.6-8. 0 mIU/ml), LH 0.8 mIU/ml (1.5-9.3 mIU/ml), Prolactin 4.1 ng/ml (4-15.2 ng/ml), TSH 1.68 mIU/ml (0.4-5.5 mIU/ml), free t4 1.2 ng/dl (0.8-1.7 ng/dl), growth hormone 0.3 ng/ml (0. 0-10 ng/ml), IGF-1 175 ng/ml (155-432 ng/ml), ACTH 14.6 pg/ml (7.2-63 pg/ml), cortisol (not am) 3. 0 ug/dl (6.2-19.4 ug/dl). Pituitary MRI revealed no focal sellar/suprasellar lesions with normal enhancement of the pituitary gland . DXA scan showed a low bone density for his age with Z-scores below -2. 0 in all regions. Chromosome analysis revealed a normal male 46, XY karyotype. Genetic testing of both patient and mother, using Invitae test kit, revealed an heterozygous mutation in FGFR1 gene, exon 9, variant c.1231C>A (p. Gln411Lys), not described in medical literature. A diagnosis of normosmic idiopathic hypogonadotropic hypogonadism (nIHH) was made. Testosterone cypionate IM 100 mg once weekly was initiated and after 6 months he experienced improvement in energy, libido, muscle mass, facial and body hair, and virilization of his voice. Conclusions The heterogeneity in phenotypic presentation of IHH makes its diagnosis a challenge. Furthermore, the genetic basis for these multiple phenotypes are still not fully described. We report a new FGFR1 mutation causing hypogonadism. Reference: Ferreira Gontijo, L., Latronico, A. Approach to the Patient With Hypogonadotropic Hypogonadism. JES, Vol. 98, Issue 5, 1 May 2013, P. 1781–1788. Presentation: No date and time listed