Novel IGSF1 mutation in three brothers with Central Hypothyroidism and Macroorchidism

BRASLAVSKY D; SCAGLIA PA; JOUSTRA, S.D.; CHIESA A; WIT, J.M.; 1; DOMENE, H.; LOSEKOOT, M.; BERGADÁ I

Playa del Carmen

Congreso; XXIV Reuniòn de la Sociedad Latinoamericana de Endocrinología Pediátrica; 2014

Sociedad Latinoamericana de Endocrinoologia Pediatrica

Introduction: IGSF1 Deficiency Syndrome is an X-linked syn- drome caused by loss-of-function mutations or deletions in Ig superfamily member 1 (IGSF1, OMIM 300888). The main clinical characteristics are congenital hypothyroidism of central origin (C-CH) and macroorchidism from late adolescence. Other fea- tures are prolactin deficiency, transient GH deficiency, delayed growth spurt and pubarche, and increased body mass index (BMI). Subjects and Methods: A family composed by 3 young adults, born to non-consanguineous parents, referred in adolescence for growth retardation and delayed puberty. Mother?s menarche 14.5 yrs. Mid-parental Height 0.4 SDS. Case 1. At 13.4 yrs: height ?0.8 SDS, BMI 1.6 SDS, Tanner stage G1, testicular volume (TV) 2/2 ml, bone age (BA) 11 yrs, TSH 5.1 mU/L, T4 4.2 ng/dl, FT4 0.55 ug/dl, Prolactin 1.8 ng/ml. Pubertal onset occurred at 14.5 yrs. GH test (at TV of 12 ml, Tanner P2, and serum testosterone (T) 230 ng/dl): GHmax 5.4 ng/ml (Normal reference >10 ng/ml). rhGH treatment started at 15.7 yr for 2.7 yrs. Case 2. At 14.0 yrs: height ?1.2 SDS, BMI 2.1 SDS, Tanner stage G1, TV 3/3 ml, BA 12.5 yrs, TSH 1.6 mU/L, T4 5.4 ng/dl, T3 94 ng/dl, Prolactin