Klinefelter's Syndrome with Maternal Uniparental Disomy X, Interstitial Xp22.31 Deletion, X-linked Ichthyosis, and Severe Central Nervous System Regression

Abstract

We presented in this article a patient with Klinefelter syndrome (KS) (47,XXY) who had maternal nondisjunction and uniparental disomy of the X chromosome with regions of heterodisomy and isodisomy, an interstitial Xp22.31 deletion of both X chromosomes, and other problems. His mother also possesses the same Xp22.31 deletion. The patient presented with status epilepticus and stroke, followed by severe brain atrophy and developmental regression. His unusual clinical and cytogenetic findings apparently have not been reported with either KS or Xp22.31 deletions. Based on the patient's available genetic and biochemical information, we cannot satisfactorily explain his seizures, strokes, or catastrophic brain regression.

Keywords

Klinefelter syndrome - maternal nondisjunction - uniparental disomy - interstitial Xp22.3 deletion - X-linked ichthyosis - status epilepticus - stroke

Publikationsverlauf

Eingereicht: 21. Mai 2020

Angenommen: 08. Juli 2020

Artikel online veröffentlicht:
20. August 2020

• References

• 1 Barr ML. The natural history of Klinefelter's syndrome. Fertil Steril 1966; 17 (04) 429-441
• 2 Klinefelter HF. Klinefelter's syndrome: historical background and development. South Med J 1986; 79 (09) 1089-1093
• 3 Graham Jr JM, Bashir AS, Stark RE, Silbert A, Walzer S. Oral and written language abilities of XXY boys: implications for anticipatory guidance. Pediatrics 1988; 81 (06) 795-806
• 4 Tatum IV WO, Passaro EA, Elia M, Guerrini R, Gieron M, Genton P. Seizures in Klinefelter's syndrome. Pediatr Neurol 1998; 19 (04) 275-278
• 5 Elia M, Musumeci SA, Ferri R, Scuderi C, Del Gracco S, Stefanini MC. Seizures in Klinefelter's syndrome: a clinical and EEG study of five patients. Ital J Neurol Sci 1995; 16 (04) 231-238
• 6 Perla C, Sánchez R, Alfaro A, Gilsanz A, Domínguez F. Striatocapsular infarct in a young patient with heterozygous familial hypercholesterolemia and Klinefelter's syndrome [in Spanish]. Med Clin (Barc) 1993; 101 (19) 746-749
• 7 Ramaswami PK, Senior DC. Klinefelter's syndrome with agenesis of kidney, diabetes, hyperlipoproteinaemia and stroke. Br J Clin Pract 1979; 33 (05) 142-143
• 8 Yoshiuchi I, Itoh N, Nakano M, Tatsumi C, Yokoyama K, Matsuyama T. Case report of Klinefelter's syndrome with severe diabetes, dyslipidemia, and stroke: the effect of pioglitazone and other anti-inflammatory agents on interleukin-6 and -8, tumor necrosis factor-alpha, and C-reactive protein. Diabetes Care 2006; 29 (08) 1981
• 9 Fukami M, Kirsch S, Schiller S. et al. A member of a gene family on Xp22.3, VCX-A, is deleted in patients with X-linked nonspecific mental retardation. Am J Hum Genet 2000; 67 (03) 563-573
• 10 Diociaiuti A, Angioni A, Pisaneschi E. et al. X-linked ichthyosis: clinical and molecular findings in 35 Italian patients. Exp Dermatol 2019; 28 (10) 1156-1163
• 11 Rodrigo-Nicolás B, Bueno-Martínez E, Martín-Santiago A. et al. Evidence of the high prevalence of neurological disorders in nonsyndromic X-linked recessive ichthyosis: a retrospective case series. Br J Dermatol 2018; 179 (04) 933-939
• 12 Doherty MJ, Glass IA, Bennett CL. et al. An Xp; Yq translocation causing a novel contiguous gene syndrome in brothers with generalized epilepsy, ichthyosis, and attention deficits. Epilepsia 2003; 44 (12) 1529-1535
• 13 Lonardo F, Parenti G, Luquetti DV. et al. Contiguous gene syndrome due to an interstitial deletion in Xp22.3 in a boy with ichthyosis, chondrodysplasia punctata, mental retardation and ADHD. Eur J Med Genet 2007; 50 (04) 301-308
• 14 Gohlke BC, Haug K, Fukami M. et al. Interstitial deletion in Xp22.3 is associated with X linked ichthyosis, mental retardation, and epilepsy. J Med Genet 2000; 37 (08) 600-602
• 15 Petit C, Melki J, Levilliers J, Serville F, Weissenbach J, Maroteaux P. An interstitial deletion in Xp22.3 in a family with X-linked recessive chondrodysplasia punctata and short stature. Hum Genet 1990; 85 (02) 247-250
• 16 Cavenagh A, Chatterjee S, Davies W. Behavioural and psychiatric phenotypes in female carriers of genetic mutations associated with X-linked ichthyosis. PLoS One 2019; 14 (02) e0212330
• 17 Mark HF, Feldman D, Sigman M. Conventional and molecular cytogenetic identification of a variant Klinefelter syndrome patient with a deleted X chromosome. Pathobiology 1999; 67 (01) 55-58
• 18 MacDonald M, Hassold T, Harvey J, Wang LH, Morton NE, Jacobs P. The origin of 47,XXY and 47,XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination. Hum Mol Genet 1994; 3 (08) 1365-1371
• 19 Fathalla WM, Mohamed K, Ahmed E. Molybdenum cofactor deficiency: report of a new case and literature review. Ibnos J Med BS 2010; 2: 133-138
• 20 Vijayakumar K, Gunny R, Grunewald S. et al. Clinical neuroimaging features and outcome in molybdenum cofactor deficiency. Pediatr Neurol 2011; 45 (04) 246-252
• 21 Schuierer G, Kurlemann G, Bick U, Stephani U. Molybdenum-cofactor deficiency: CT and MR findings. Neuropediatrics 1995; 26 (01) 51-54
• 22 Papenhausen P, Schwartz S, Risheg H. et al. UPD detection using homozygosity profiling with a SNP genotyping microarray. Am J Med Genet A 2011; 155A [phone]
• 23 Yamazawa K, Ogata T, Ferguson-Smith AC. Uniparental disomy and human disease: an overview. Am J Med Genet C Semin Med Genet 2010; 154C [phone]
• 24 Ben Khelifa H, Soyah N, Ben-Abdallah-Bouhjar I. et al. Xp22.3 interstitial deletion: a recognizable chromosomal abnormality encompassing VCX3A and STS genes in a patient with X-linked ichthyosis and mental retardation. Gene 2013; 527 (02) 578-583
• 25 Meindl A, Hosenfeld D, Brückl W. et al. Analysis of a terminal Xp22.3 deletion in a patient with six monogenic disorders: implications for the mapping of X linked ocular albinism. J Med Genet 1993; 30 (10) 838-842
• 26 Kent L, Emerton J, Bhadravathi V. et al. X-linked ichthyosis (steroid sulfatase deficiency) is associated with increased risk of attention deficit hyperactivity disorder, autism and social communication deficits. J Med Genet 2008; 45 (08) 519-524
• 27 Tiepolo L, Zuffardi O, Fraccaro M. et al. Assignment by deletion mapping of the steroid sulfatase X-linked ichthyosis locus to Xp223. Hum Genet 1980; 54 (02) 205-206
• 28 Boycott KM, Parslow MI, Ross JL, Miller IP, Bech-Hansen NT, MacLeod PM. A familial contiguous gene deletion syndrome at Xp22.3 characterized by severe learning disabilities and ADHD. Am J Med Genet A 2003; 122A [phone]