The IGSF1 Deficiency Syndrome: Characteristics of Male and Female Patients

SD Joustra, N Schoenmakers, L Persani, I Campi, M Bonomi, G Radetti, P Beck-Peccoz, H Zhu, TME Davis, Y Sun, EP Corssmit, NM Appelman-Dijkstra, CA Heinen, AM Pereira, Aimee Varewijck, J.A.M.J.L. Janssen, E Endert, RC Hennekam, MP Lombardi, MMAM MannensB Bak, DJ Bernard, MH Breuning, K Chatterjee, MT Dattani, W oostdijk, NR Biermasz, JM Wit, ASP van Trotsenburg

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Context: Ig superfamily member1 (IGSF1) deficiency was recently discovered as a novel X-linked cause of central hypothyroidism (CeH) and macro-orchidism. However, clinical and biochemical data regarding growth, puberty, and metabolic outcome, as well as features of female carriers, are scarce. Objective: Our objective was to investigate clinical and biochemical characteristics associated with IGSF1 deficiency in both sexes. Methods: All patients (n = 42, 24 males) from 10 families examined in the university clinics of Leiden, Amsterdam, Cambridge, and Milan were included in this case series. Detailed clinical data were collected with an identical protocol, and biochemical measurements were performed in a central laboratory. Results: Male patients (age 0-87 years, 17 index cases and 7 from family studies) showed CeH (100%), hypoprolactinemia (n = 16, 67%), and transient partial GH deficiency (n = 3, 13%). Pubertal testosterone production was delayed, as were the growth spurt and pubic hair development. However, testicular growth started at a normal age and attained macro-orchid size in all evaluable adults. Body mass index, percent fat, and waist circumference tended to be elevated. The metabolic syndrome was presen Conclusion: In male patients, the X-linked IGSF1 deficiency syndrome is characterized by CeH, hypoprolactinemia, delayed puberty, macro-orchidism, and increased body weight. A subset of female carriers also exhibits CeH.
Original languageUndefined/Unknown
Pages (from-to)4942-4952
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Issue number12
Publication statusPublished - 2013

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  • EMC MM-01-39-01

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