Hypogonadotropic hypogonadism and cerebellar ataxia: detailed phenotypic characterization of a large, extended kindred

The Journal of Clinical Endocrinology and Metabolism
Stephanie B SeminaraDavid H Margolin

Abstract

Although the co-occurrence of cerebellar ataxia and hypogonadism has been recognized for close to 100 yr, cases of Gordon Holmes syndrome are quite rare. This report describes the largest kindred characterized to date. The parents of the three affected siblings are first cousins, suggesting that the disease was inherited as an autosomal recessive trait. The siblings' initial evaluation was notable for low serum levels of sex steroids and gonadotropins (consistent with hypogonadotropic hypogonadism), progressive ataxia, and dementia. Extended treatment with physiological doses of pulsatile GnRH failed to stimulate a gonadotropin response. Brain imaging revealed volume loss in the cerebellum, with extensive abnormalities in the cerebral white matter. This unique family suggests that a common genetic mechanism is responsible for the syndrome of progressive hypogonadotropism and cerebellar ataxia.

References

Jan 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·R J MullenR L Sidman
Jan 1, 1990·Clinical Neurology and Neurosurgery·G De MicheleD Mansi
Mar 1, 1990·Ophthalmic Paediatrics and Genetics·G A ChrousosR J Sherins
Sep 1, 1990·Journal of the Neurological Sciences·R AbsJ J Martin
Mar 1, 1989·Journal of Neurology, Neurosurgery, and Psychiatry·A C FokJ S Cheah
Nov 1, 1989·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·C J Partsch, W G Sippell
Jun 1, 1986·The Journal of Clinical Endocrinology and Metabolism·M FilicoriW F Crowley
Nov 23, 1985·British Medical Journal·N A AdulwahidH S Jacobs
Oct 1, 1973·The Journal of Clinical Investigation·R J Santen, C W Bardin
Aug 1, 1982·Journal of Neurology, Neurosurgery, and Psychiatry·J BercianoA Vaquero
Jan 1, 1994·Alzheimer Disease and Associated Disorders·A LennoxJ M Berg
Aug 1, 1997·Human Molecular Genetics·L MonterminiS Cocozza
May 20, 1998·Neuropsychology Review·M D ThompsonC J Golden
Jun 9, 2000·Annual Review of Neuroscience·H Y Zoghbi, H T Orr
Jun 1, 2001·Journal of Neurology, Neurosurgery, and Psychiatry·R H McShaneA D Smith
Aug 1, 1960·The Journal of Clinical Endocrinology and Metabolism·A HECHT, H RUSKIN

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Citations

May 10, 2013·The New England Journal of Medicine·David H MargolinStephanie B Seminara
Jul 2, 2008·The Cerebellum·Asher J AlbertsonDonal C Skinner
Mar 6, 2007·Reviews in Endocrine & Metabolic Disorders·Felecia Cerrato, Stephanie B Seminara
Nov 2, 2006·Pituitary·Paola Ascoli, Francesco Cavagnini
Jul 21, 2004·Parkinsonism & Related Disorders·Martin Viau, Yvan Boulanger
Dec 17, 2005·Annales d'endocrinologie·R DesailloudB Simovic-Corroyer
May 3, 2016·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Manuel NistalMiguel Reyes-Múgica
Mar 27, 2010·Arquivos de neuro-psiquiatria·Pedro Braga-NetoOrlando Graziani Povoas Barsottini
Dec 6, 2017·Brain : a Journal of Neurology·Franziska HocheJeremy D Schmahmann
Aug 16, 2014·American Journal of Medical Genetics. Part a·Celine Pebrel-RichardPhilippe Vago
Jun 30, 2018·BMJ Case Reports·Rajesh VermaShinu Singla
Jul 13, 2007·Pituitary·Ericka Barbosa TrarbachAna Claudia Latronico
Oct 4, 2017·Practical Neurology·Shahid MehmoodMarios Hadjivassiliou
May 23, 2020·The Cerebellum·Luis E Almaguer-MederosAnnelié Rodríguez-Estupiñán
Dec 31, 2004·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·N A GeorgopoulosV A Tzingounist
Feb 4, 2009·Journal of Neuroendocrinology·D C SkinnerN Scanlan-Blake
Jun 23, 2021·Clinical Neurology and Neurosurgery·Sara LocciAndrea Mignarri
Nov 4, 2021·The Journal of Clinical Investigation·Danielle E WhittakerMehul T Dattani

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