Table 2.
Genetic Basis of GnRH Deficiency and Associated Features
| OMIM ID | Isolated | KS | Syndromic | Pathogenic Variants | Associated Variants | |
|---|---|---|---|---|---|---|
| Primary/congenital | ||||||
| GNRHR/GNRH1 | 138850/152760 | X | x | |||
| KISS1R/KISS1 | 604161/603286 | X | x | |||
| TACR3/TAC3 | 162332/162330 | X | x | x | ||
| FGFR1/FGF8 | 136350/600483 | X | x | Hartsfield | x | x |
| FGF17 | 603725 | X | x | x | ||
| ANOS1 (KAL1) | 300836 | x | x | |||
| HS6ST1 | 604846 | X | x | x | ||
| IL17RD | 606807 | x | x | |||
| DUSP6 | 602748 | X | x | x | ||
| SPRY4 | 607984 | X | x | x | ||
| FLRT3 | 604808 | x | x | |||
| PROKR2/PROK2 | 607123/607002 | x | x | |||
| SEMA3A/SEMA3E/SEMA7A | 603961/608166/607961 | x | x | |||
| WDR11 | 606417 | X | x | x | ||
| CCDC141 | 616031 | X | x | x | ||
| LEPR/LEP | 601007/164160 | Severe obesity | x | |||
| PCSK1 | 162150 | Obesity, ACTH deficiency, diabetes | x | |||
| DMXL2 | 616113 | Polyendocrinopathy-polyneuropathy syndrome | x | |||
| RNF216/OTUD4 | 609948/611744 | x | Gordon Holmes | x | ||
| PNPLA6 | 603197 | x | Gordon Holmes, Oliver–Mcfarlane, Laurence–Moon | x | ||
| SOX10 | 602229 | x | Waardenburg | x | ||
| FEZF1 | 613301 | x | x | |||
| CHD7 | 608892 | X | x | CHARGE | x | |
| POLR3A/POLR3B | 614258/614366 | 4H | x | |||
| LHB | 152780 | X | x | |||
| FSHB | 136530 | X | x | |||
| NR0B1 | 300473 | Adrenal hypoplasia | x | |||
| Associated with other pituitary hormone deficiencies | ||||||
| Congenital | With or without midline defects; with or without developmental defects | |||||
| Secondary | Tumors: craniopharyngioma, germinoma, astrocytoma, glioma | |||||
| Rathke pouch cyst | ||||||
| Brain (pituitary) irradiation | ||||||
| Head trauma | ||||||
| Infiltrative diseases: hemochromatosis, histiocytosis, sarcoidosis | ||||||
| Functional, secondary to | Chronic diseases: gastrointestinal (celiac disease, inflammatory bowel disease) Endocrinopathies: hypothyroidism, hyperprolactinemia, GH deficiency Psychiatric illness: anorexia nervosa Excessive exercise, undernutrition | |||||