Table 4. [Syndromes Associated with Hypogonadotropic Hypogonadism]. - GeneReviews®

Syndrome	Genetic Mechanism / Associated Gene	Phenotype	Reference
Bardet-Biedl syndrome	Pathogenic variants in of one of 19 genes ¹	Developmental delay, visual impairment, postaxial polydactyly, obesity, renal impairment
CHARGE syndrome	CHD7	Coloboma, heart defect, choanal atresia, growth retardation, ear abnormalities	Pinto et al [2005], Lalani & Belmont [2009]
Combined pituitary hormone deficiency	HESX1	Various degrees of hypopituitarism	PROP1-Related Combined Pituitary Hormone Deficiency, Differential Diagnosis: Combined Pituitary Hormone Deficiencies
LHX3
LHX4
POU1F1
PROP1
Gordon-Holmes syndrome	OTUD4 PNPLA6 RNF216 STUB1	Cerebellar ataxia, dementia	Seminara et al [2002], Margolin et al [2013]
HFE-associated hereditary hemochromatosis	HFE	Cirrhosis, diabetes, cardiomyopathy, arthritis, skin hyperpigmentation
Obesity syndromes	PCSK1 (PC1)	Morbid obesity, hypocortisolism, hypoinsulinemia	Jackson et al [1997], Jackson et al [2003]
LEP	Morbid obesity	Strobel et al [1998]
LEPR	Clément et al [1998]
Prader-Willi syndrome	Loss of paternal 15q11.2	Hypotonia in infancy, developmental delay, cryptorchidism/microphallus in males, abnormal satiety, intellectual disability	Cassidy et al [2012]
TUBB3 E410K syndrome (See Tubulinopathies Overview.)	TUBB3	Congenital fibrosis of the extraocular muscles, facial weakness, developmental delay, sensorimotor polyneuropathy, stereotyped midface hypoplasia, intellectual disabilities & vocal cord paralysis, tracheomalacia & cyclic vomiting	Chew et al [2013], Balasubramanian et al [2015]
X-linked adrenal hypoplasia congenita	NR0B1	Adrenal failure
Xp22.3 contiguous gene deletion syndrome	Xp22.3 microdeletion	KS, icthyosis, short stature, intellectual disability, chondrodysplasia punctata, digital synkinesia	Bick et al [1989], Hou [2005]

Syndrome

Genetic Mechanism / Associated Gene

Phenotype

Reference

Bardet-Biedl syndrome

Pathogenic variants in of one of 19 genes ¹

Developmental delay, visual impairment, postaxial polydactyly, obesity, renal impairment

CHARGE syndrome

CHD7

Coloboma, heart defect, choanal atresia, growth retardation, ear abnormalities

Pinto et al [2005], Lalani & Belmont [2009]

Combined pituitary hormone deficiency

HESX1

Various degrees of hypopituitarism

PROP1-Related Combined Pituitary Hormone Deficiency, Differential Diagnosis: Combined Pituitary Hormone Deficiencies

LHX3

LHX4

POU1F1

PROP1

Gordon-Holmes syndrome

OTUD4
PNPLA6
RNF216
STUB1

Cerebellar ataxia, dementia

Seminara et al [2002], Margolin et al [2013]

HFE-associated hereditary hemochromatosis

HFE

Cirrhosis, diabetes, cardiomyopathy, arthritis, skin hyperpigmentation

Obesity syndromes

PCSK1 (PC1)

Morbid obesity, hypocortisolism, hypoinsulinemia

Jackson et al [1997], Jackson et al [2003]

LEP

Morbid obesity

Strobel et al [1998]

LEPR

Clément et al [1998]

Prader-Willi syndrome

Loss of paternal 15q11.2

Hypotonia in infancy, developmental delay, cryptorchidism/microphallus in males, abnormal satiety, intellectual disability

Cassidy et al [2012]

TUBB3 E410K syndrome (See Tubulinopathies Overview.)

TUBB3

Congenital fibrosis of the extraocular muscles, facial weakness, developmental delay, sensorimotor polyneuropathy, stereotyped midface hypoplasia, intellectual disabilities & vocal cord paralysis, tracheomalacia & cyclic vomiting

Chew et al [2013], Balasubramanian et al [2015]

X-linked adrenal hypoplasia congenita

NR0B1

Adrenal failure

Xp22.3 contiguous gene deletion syndrome

Xp22.3 microdeletion

KS, icthyosis, short stature, intellectual disability, chondrodysplasia punctata, digital synkinesia

Bick et al [1989], Hou [2005]

From: Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

Seattle (WA): University of Washington, Seattle; 1993-2024.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.