GLI2 |
Dominant |
IGHD or CPHD |
↓ |
Ectopic/NV |
Polydactyly, HPE, craniofacial malformations |
(1616. Franca MM, Jorge AA, Carvalho LR, Costalonga EF, Vasques GA, Leite CC, et al. Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and ectopic posterior pituitary lobe without holoprosencephaly. J Clin Endocrinol Metab. 2010;95(11):E384-91.) |
FGF8 |
Recessive |
HH, IGHD or CPHD |
↑ or NL |
Topic |
SOD, HPE, KS, Moebius syndrome |
(1818. McCabe MJ, Gaston-Massuet C, Tziaferi V, Gregory LC, Alatzoglou KS, Signore M, et al. Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction. J Clin Endocrinol Metab. 2011;96(10):E1709-18.) |
FGFR1 |
Dominant |
HH or CPHD |
NL or ↓ |
Ectopic or Topic |
SOD, midline craniofacial malformations, corpus callosum abnormalities |
(1717. Raivio T, Avbelj M, McCabe MJ, Romero CJ, Dwyer AA, Tommiska J, et al. Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab. 2012;97(4):E694-9.) |
PAX6 |
Dominant |
IGHD or CPHD |
↓ |
Topic |
Midline craniofacial malformations, ophthalmologic abnormalities |
(5858. Takagi M, Nagasaki K, Fujiwara I, Ishii T, Amano N, Asakura Y, et al. Heterozygous defects in PAX6 gene and congenital hypopituitarism. Eur J Endocrinol. 2015;172(1):37-45.) |
GLI3 |
Dominant |
IGHD or CPHD |
A or ↓ |
Topic |
Pallister-Hall syndrome |
(5959. Johnston JJ, Sapp JC, Turner JT, Amor D, Aftimos S, Aleck KA, et al. Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations. Hum Mutat. 2010;31(10): 1142-54.) |
ARNT2 |
Recessive |
CPHD |
↓ |
Topic |
Brain, eye, kidney and urinary tract abnormalities, corpus callosum abnormalities |
(2020. Webb EA, AlMutair A, Kelberman D, Bacchelli C, Chanudet E, Lescai F, et al. ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies. Brain. 2013;136(Pt 10):3096-105.) |
CDON |
Dominant |
CPHD |
A |
Topic or Ectopic |
HPE, maternal ethanol exposure worsens the phenotype |
(2222. Bashamboo A, Bignon-Topalovic J, Rouba H, McElreavey K, Brauner R. A nonsense mutation in the hedgehog receptor CDON associated with pituitary stalk interruption syndrome. J Clin Endocrinol Metab. 2016;101(1):12-5.) |
GPR161 |
Recessive |
IGHD or CPHD |
↓ |
Ectopic |
|
(6060. Karaca E, Buyukkaya R, Pehlivan D, Charng WL, Yaykasli KO, Bayram Y, et al. Whole-exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome. J Clin Endocrinol Metab. 2015;100(1):E140-7.) |
IGSF1 |
X-linked |
CPHD |
NL |
Topic |
Macroorchidism, undetectable prolactin |
(2121. Sun Y, Bak B, Schoenmakers N, van Trotsenburg AS, Oostdijk W, Voshol P, et al. Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement. Nat Genet. 2012;44(12):1375-81.) |
PROKR2 |
Dominant or recessive |
HH, IGHD or CPHD |
NL or ↓ |
Topic or Ectopic |
SOD, Hirschsprung disease |
(1717. Raivio T, Avbelj M, McCabe MJ, Romero CJ, Dwyer AA, Tommiska J, et al. Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab. 2012;97(4):E694-9.) |
TGIF1 |
Dominant |
CPHD |
↓ |
Ectopic |
HPE, midline craniofacial malformations |
(6161. Tatsi C, Sertedaki A, Voutetakis A, Valavani E, Magiakou MA, Kanaka-Gantenbein C, et al. Pituitary stalk interruption syndrome and isolated pituitary hypoplasia may be caused by mutations in holoprosencephaly-related genes. J Clin Endocrinol Metab. 2013;98(4):E779-84.) |
TCF7L1 |
Dominant |
IGHD |
↓ |
NV |
SOD |
(6262. Gaston-Massuet C, McCabe MJ, Scagliotti V, Young RM, Carreno G, Gregory LC, et al. Transcription factor 7-like 1 is involved in hypothalamo-pituitary axis development in mice and humans. Proc Natl Acad Sci U S A. 2016;113(5):E548-57.) |
PROK2 |
Dominant |
CPHD |
NL |
Ectopic |
Digenic |
(1414. Zwaveling-Soonawala N, Alders M, Jongejan A, Kovacic L, Duijkers FA, Maas SM, et al. Clues for polygenic inheritance of pituitary stalk interruption syndrome from exome sequencing in 20 patients. J Clin Endocrinol Metab. 2018;103(2):415-28.) |