This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Seminara, S. B. Articles by Margolin, D. H. Search for Related Content PubMed PubMed Citation Articles by Seminara, S. B. Articles by Margolin, D. H.

Hypogonadotropic Hypogonadism and Cerebellar Ataxia: Detailed Phenotypic Characterization of a Large, Extended Kindred

Reproductive Endocrine Unit (S.B.S., J.S.A., N.A.A., W.F.C.) and Department of Neurology (D.H.M.), Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Stephanie Seminara, M.D., Reproductive Endocrine Unit, Bartlett Hall Extension 505, Massachusetts General Hospital, Fruit Street, Boston, Massachusetts 02114. E-mail: . seminara.stephanie{at}mgh.harvard.edu

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.

This article has been cited by other articles:

				M. Timmons, M. Tsokos, M. A. Asab, S. B. Seminara, G. C. Zirzow, C. R. Kaneski, J. D. Heiss, M. S. van der Knaap, M. T. Vanier, R. Schiffmann, et al. Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia Neurology, December 12, 2006; 67(11): 2066 - 2069. [Abstract] [Full Text] [PDF]

				G J Breedveld, B van Wetten, G D te Raa, E Brusse, J C van Swieten, B A Oostra, and J A Maat-Kievit A new locus for a childhood onset, slowly progressive autosomal recessive spinocerebellar ataxia maps to chromosome 11p15 J. Med. Genet., November 1, 2004; 41(11): 858 - 866. [Full Text] [PDF]