Chromosomal Abnormalities and Hydrocephalus: Could There Be an Association between Klinefelter's Syndrome and Idiopathic Normal-Pressure Hydrocephalus?

Alessandro Pesce; Graziano Taddei; Mauro Palmieri; Silvia Ciarlo; Rita Carnevale; Stefania Elia; Angelo Pompucci; Gianpaolo Petrella

doi:10.1055/s-0045-1810046

Journal of Neurological Surgery Part A: Central European Neurosurgery, Table of Contents

J Neurol Surg A Cent Eur Neurosurg 2025; 86(06): 591-595
DOI: 10.1055/s-0045-1810046

Case Report

Chromosomal Abnormalities and Hydrocephalus: Could There Be an Association between Klinefelter's Syndrome and Idiopathic Normal-Pressure Hydrocephalus?

Authors

Alessandro Pesce

⁵Department of Systems Medicine, Univerisity of Rome, Tor Vergata, Italy
Graziano Taddei

¹Department of Neurosurgery, Santa Maria Goretti Hospital, Latina, Italy
Mauro Palmieri

²Human Neurosciences Department, Neurosurgery Division, University Sapienza of Rome, Italy
Silvia Ciarlo

¹Department of Neurosurgery, Santa Maria Goretti Hospital, Latina, Italy

³School of Neurosurgery, University of Messina, Italy
Rita Carnevale

⁴Nursing School, University Sapienza of Rome, Italy
Stefania Elia

⁴Nursing School, University Sapienza of Rome, Italy
Angelo Pompucci

¹Department of Neurosurgery, Santa Maria Goretti Hospital, Latina, Italy
Gianpaolo Petrella

¹Department of Neurosurgery, Santa Maria Goretti Hospital, Latina, Italy

Abstract

Idiopathic normal-pressure hydrocephalus shows a typical clinical triad consisting of gait disturbance, dementia, and urinary incontinence, often combined with ventriculomegaly. Fortunately, these clinical manifestations are potentially reversible by adequate surgical treatment. Men affected by Klinefelter's syndrome can present cognitive problems. These include impairments in both verbal and nonverbal memory and in executive functions, which could be related to idiopathic normal-pressure hydrocephalus in these patients. In this study, we describe the case of a 62-year-old-man genetically diagnosed with Klinefelter's syndrome with a history of gait ataxia resulting in recurrent falls. Direct associations between idiopathic normal-pressure hydrocephalus and Klinefelter's syndrome and clinical pathophysiologic and potential molecular implications are discussed.

Keywords

Klinefelter's syndrome - idiopathic normal-pressure hydrocephalus - dementia

Full Text

References

References
1 Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH. Symptomatic occult hydrocephalus with “normal” cerebrospinal-fluid pressure. A treatable syndrome. N Engl J Med 1965; 273: 117-126
2 Jaraj D, Rabiei K, Marlow T, Jensen C, Skoog I, Wikkelsø C. Prevalence of idiopathic normal-pressure hydrocephalus. Neurology 2014; 82 (16) 1449-1454
3 Gavrilov GV, Gaydar BV, Svistov DV. et al. Idiopathic normal pressure hydrocephalus (Hakim-Adams syndrome): clinical symptoms, diagnosis and treatment. Psychiatr Danub 2019; 31 (Suppl. 05) 737-744
4 Bräutigam K, Vakis A, Tsitsipanis C. Pathogenesis of idiopathic normal pressure hydrocephalus: a review of knowledge. J Clin Neurosci 2019; 61: 10-13
5 Klinefelter HF, Reifenstein EC, Albright F. Syndrome characterized by gynecomastia, aspermatogenesis without a-Leydigism, and increased excretion of follicle-stimulating hormone. J Clin Endocrinol Metab 1942; 2 (11) 615-627
6 Mehmet B, Gillard S, Jayasena CN, Llahana S. Association between domains of quality of life and patients with Klinefelter syndrome: a systematic review. Eur J Endocrinol 2022; 187 (02) S21-S34
7 Groth KA, Skakkebæk A, Høst C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome: a clinical update. J Clin Endocrinol Metab 2013; 98 (01) 20-30
8 Marano M, Pompucci A, Motolese F. et al. Normal pressure hydrocephalus in down syndrome: the report of two cases. J Alzheimers Dis 2020; 77 (03) 979-984
9 Anile C, De Bonis P, Albanese A. et al. Selection of patients with idiopathic normal-pressure hydrocephalus for shunt placement: a single-institution experience. J Neurosurg 2010; 113 (01) 64-73
10 Nakajima M, Yamada S, Miyajima M. et al. Research Committee of Idiopathic Normal Pressure Hydrocephalus. Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): endorsed by the Japanese Society of Normal Pressure Hydrocephalus. Neurol Med Chir (Tokyo) 2021; 61 (02) 63-97
11 Boltshauser E, Meyer M, Deonna T. Klinefelter syndrome and neurological disease. J Neurol 1978; 219 (04) 253-259
12 Funakawa I, Miyao S, Takayanagi T. Klinefelter syndrome with communicating hydrocephalus: a case report. Rinsho Shinkeigaku 1985; 25 (08) 960-964
13 Turliuc MD, Cucu AI, Perciaccante A. et al. Hydrocephalus of King Charles II of Spain, the bewitched king. Eur Neurol 2019; 81 (1–2): 76-78
14 Tatum IV WOT, Passaro EA, Elia M, Guerrini R, Gieron M, Genton P. Seizures in Klinefelter's syndrome. Pediatr Neurol 1998; 19 (04) 275-278
15 Sasaki R, Ohta Y, Takahashi Y. et al. A rare case of Klinefelter syndrome accompanied by spastic paraplegia and peripheral neuropathy. Intern Med 2019; 58 (03) 437-440
16 Skakkebæk A, Gravholt CH, Rasmussen PM. et al. Neuroanatomical correlates of Klinefelter syndrome studied in relation to the neuropsychological profile. Neuroimage Clin 2013; 4: 1-9
17 Foland-Ross LC, Gil M, Shrestha SB, Chromik LC, Hong D, Reiss AL. Cortical gray matter structure in boys with Klinefelter syndrome. Psychiatry Res Neuroimaging 2021; 313: 111299
18 Hong DS, Hoeft F, Marzelli MJ. et al. Influence of the X-chromosome on neuroanatomy: evidence from Turner and Klinefelter syndromes. J Neurosci 2014; 34 (10) 3509-3516
19 Ji W, Tang Z, Chen Y. et al. Ependymal cilia: physiology and role in hydrocephalus. Front Mol Neurosci 2022; 15: 927479
20 Serra R, Simard JM. Adherens, tight, and gap junctions in ependymal cells: a systematic review of their contribution to CSF-brain barrier. Front Neurol 2023; 14: 1092205
21 Condorelli RA, Calogero AE, La Vignera S. Different profile of endothelial cell apoptosis in patients with Klinefelter's syndrome. J Endocrinol Invest 2013; 36 (02) 84-91
22 Haymana C, Aydogdu A, Demirci I. et al. Increased endothelial dysfunction and insulin resistance in patients with Klinefelter syndrome. Endocr Metab Immune Disord Drug Targets 2018; 18 (04) 401-406
23 Al-Dosari MS, Al-Owain M, Tulbah M. et al. Mutation in MPDZ causes severe congenital hydrocephalus. J Med Genet 2013; 50 (01) 54-58
24 Baltzegar DA, Reading BJ, Brune ES, Borski RJ. Phylogenetic revision of the claudin gene family. Mar Genomics 2013; 11: 17-26
25 Tully HM, Dobyns WB. Infantile hydrocephalus: a review of epidemiology, classification and causes. Eur J Med Genet 2014; 57 (08) 359-368
26 Walsh FS, Barton CH, Putt W. et al. N-cadherin gene maps to human chromosome 18 and is not linked to the E-cadherin gene. J Neurochem 1990; 55 (03) 805-812
27 Feldner A, Adam MG, Tetzlaff F. et al. Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice. EMBO Mol Med 2017; 9 (07) 890-905
28 Wyss L, Schäfer J, Liebner S. et al. Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus. PLoS One 2012; 7 (09) e45619