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Pentasomy X

April 14, 2024

Pentasomy X, also known as 49,XXXXX, is a chromosomal disorder in which a female has five, rather than two, copies of the X chromosome. Pentasomy X is associated with short stature, intellectual disability, characteristic facial features, heart defects, skeletal anomalies, and pubertal and reproductive abnormalities. The condition is exceptionally rare, with an estimated prevalence between 1 in 85,000 and 1 in 250,000.

Pentasomy X
Other names49,XXXXX
Karyotype of pentasomy X
SpecialtyMedical genetics 
SymptomsIntellectual disability, facial dysmorphisms, heart defects
Usual onsetConception
DurationLifelong
CausesNondisjunction
Diagnostic methodKaryotype

The condition has a large variety of symptoms, and it is difficult to paint a conclusive portrait of its phenotypes. Though significant disability is characteristic, there are so few diagnosed cases that confident conclusions about the presentation and prognosis remain impossible. Pentasomy X may be mistaken for more common chromosomal disorders, such as Down syndrome or Turner syndrome, before a conclusive diagnosis is reached.

Pentasomy X is not inherited but rather occurs via nondisjunction, a random event in gamete development. In rare cases, it may be related to a parent's chromosomal mosaicism. The karyotype observed in pentasomy X is formally known as 49,XXXXX, which represents the 49 chromosomes observed in the disorder as compared to the 46 in normal human development.

Presentation edit

The major clinical features of pentasomy X are intellectual disability, short stature, facial and musculoskeletal abnormalities, and congenital heart defects.[1] Although one recorded case has been of low average intelligence,[2] all other known cases have been intellectually disabled, with an average IQ of 50.[1] The overall portrait is one of moderate intellectual disability,[3] defined by an adult cognitive capacity similar to that of a six- to eight-year-old and the ability to acquire basic living and employment skills with support.[4] Some girls with pentasomy X attend special education in mainstream schools through mainstreaming or inclusion, while some attend special schools.[3]

 
A 15-year-old girl with pentasomy X, demonstrating facial, limb, and skeletal features

Pentasomy X is associated with a number of physical anomalies, including short stature, clinodactyly (incurved pinky fingers), and distinctive facial features. Common findings include microcephaly, low-set ears, hypertelorism (wide-spaced eyes), and epicanthic folds.[5] The characteristic facies have been described as "coarse",[1] much like those of the related disorder tetrasomy X.[6] Pentasomy X is unique amongst X-chromosome polysomies for its association with short stature, when most related disorders are associated with tall stature;[7] the average height in pentasomy X is one standard deviation below the norm.[8] Hypotonia, often severe, is a frequent finding, as are related musculoskeletal issues such as hip dysplasia.[9] The severity of repeated joint dislocations may lead to a differential diagnosis of Larsen syndrome, as suggested in one reported case.[10] Bone maturation may be delayed.[11] Another skeletal finding is taurodontism, where the pulp of the teeth is enlarged into the roots;[5] other dental abnormalities, such as missing teeth and severe tooth decay, have also been reported.[12] These findings are not specific to pentasomy X, but rather common to sex chromosome aneuploidies in general and in particular show a strong resemblance to the male counterpart 49,XXXXY.[13] Epicanthic folds and hypertelorism are also observed in tetrasomy and trisomy X,[7] while clinodactyly and radioulnar synostosis are seen in all sex chromosome aneuploidies[1][14][15] and taurodontism is specifically common to X-chromosome polysomies.[16]

Heart defects are associated with the syndrome. Pentasomy X has one of the highest rates of congenital heart defects of any chromosomal disorder, with 56.5% of recorded patients having a heart defect of some kind. Patent ductus arteriosus is particularly frequent.[3][17] The majority of such conditions resolve without surgical treatment, although a minority require it.[3] Ventricular septal defects are also frequent.[1] Other internal medical issues frequently recorded include kidney and urinary defects.[3] Epilepsy has been associated with the condition,[18] though seems to be rare.[3] In sex chromosome aneuploidies as a whole, epilepsy is usually mild and amenable to treatment,[19] and reports of epilepsy in pentasomy X have described it resolving with treatment and allowing antiepileptic drugs to eventually be stopped.[3]

Puberty is altered in pentasomy X, although as few adults with the condition have been reported, the full scope of such alterations is unclear. In the sister condition of tetrasomy X, half of all women undergo puberty normally, while half have no or incomplete puberty.[1] Some adolescents and adults with pentasomy X have been prepubertal,[1] while some have had premature ovarian failure (early menopause)[20] and some have had apparently non-noteworthy pubertal development.[21][22] Though external genitalia is generally normal, underlying gonadal dysfunction is frequent, including ovarian dysfunction or an unusually small uterus.[17] No cases are known of women with pentasomy X having children, but although fertility is likely reduced, some may be able to.[23]

Little is understood about the psychological and behavioural phenotype of pentasomy X. Girls and women with the disorder are frequently described as shy and cooperative.[1] Such traits are common to other conditions involving extra copies of the X chromosome.[15][24] Developmental delays can cause difficulty communicating, resulting in frustration and tantrums. Overall, the syndrome is not associated with severe behavioural issues.[3]

A number of disorders have been reported as comorbid with sex chromosome aneuploidies, including pentasomy X. In one case report, pentasomy X occurred alongside the similarly rare hyperimmunoglobulin E syndrome.[25] Other possibly coincidental associations have included cerebral palsy[22] and Dandy–Walker malformation.[26]

Causes edit

 
Maternal age in 21 cases of pentasomy X, showing the unclear relationship

Pentasomy X is caused by nondisjunction, a process through which gametes (eggs or sperm) with too many or too few chromosomes are produced. In nondisjunction, homologous chromosomes or sister chromatids fail to separate properly when producing gametes.[27] In sex chromosome tetrasomy and pentasomy, the extra chromosomes are consistently inherited from one parent.[1] In the specific case of pentasomy X, all known cases have inherited the additional chromosomes from the mother. This has been suggested to relate to genomic imprinting; specifically, it is hypothesized that specific loci on the sex chromosomes are affected by imprinting such that only maternal overimprinting is survivable, and cases of pentasomy X where the additional chromosomes were inherited from the father would be incompatible with life.[28] As well as during gamete development, nondisjunction can occur after conception, resulting in a mosaic karyotype.[29]

Nondisjunction is related to advanced maternal age,[30] although due to its rarity, the maternal age effect in pentasomy X is unclear.[31] More common aneuploidy syndromes, such as Down syndrome and Klinefelter's syndrome, have strong relationships with maternal age.[32][33] Pentasomy X is not inherited[5] and is not caused by the actions of the parents.[34] However, in rare cases, pentasomy X may be related to chromosomal mosaicism in a parent.[3][35]

X inactivation is a major factor in pentasomy X. X inactivation is the process through which genes in second (or higher) copies of the X chromosome are turned off, such that any cell has only one active copy of the chromosome.[36] However, X inactivation appears to be disrupted in pentasomy X, allowing up to half of the supposedly inactive genetic material to actually work. This is assumed to contribute to the severe phenotype of the condition compared to other sex chromosome aneuploidies.[21]

Diagnosis edit

Chromosome aneuploidies such as pentasomy X are diagnosed through the process of karyotyping, or chromosome testing.[37] Diagnosis cannot be made on the basis of phenotype alone, as multiple other conditions present similarly.[1]

The phenotype of pentasomy X is not specific to the disorder, and many other conditions can be differential diagnoses. One is tetrasomy X, a related disorder in which a girl or woman has four copies of the X chromosome. The general profiles of the conditions are similar, with developmental delays, mild dysmorphic features, and shared congenital anomalies such as clinodactyly and radioulnar synostosis. However, the phenotype of pentasomy X is more severe than that of tetrasomy X, with lower IQ and more severe dysmorphism. Pentasomy X also has additional characteristics uncommon in the tetrasomy, such as short stature.[1][7] Mosaic karyotypes, with both 48,XXXX and 49,XXXXX cells, are also possible. Though very few mosaic cases have been reported, the phenotype appears intermediate in severity between tetrasomy and pentasomy X.[9]

Another potential differential diagnosis is Down syndrome. The features of the two conditions overlap, and some girls with pentasomy X may be assumed to have Down's before genetic ascertainment.[5] Some cases of pentasomy X have had family histories of Down syndrome, inciting speculation that the conditions may tend to recur in the same family lines; alternatively, it may suggest that some patients diagnosed with Down syndrome on the basis of phenotype may actually have pentasomy X.[17]

The phenotype of pentasomy X has also been compared to that of Turner syndrome, characterized by a female having one copy of the X chromosome. Both Turner's and pentasomy X are female-only disorders characterized by short stature, heart defects, and abnormal pubertal development. However, the intellectual disabilities observed in pentasomy X are rare in Turner syndrome.[5]

Prognosis edit

The long-term prognosis of pentasomy X is unclear, due to its low prevalence.[1] Though some reviews claim a poor prognosis due to the congenital defects observed in severe cases,[9] support groups report milder abnormalities than common in the medical literature, including adults with pentasomy X in fair health.[3] The spectrum of severity varies; long-term support is consistent, though some women have been reported as being able to work part-time and manage some of their affairs.[18] For sex chromosome tetrasomy and pentasomy disorders as a whole, good prognosis is linked to strong parental and personal support. Girls and women with pentasomy X whose caregivers have acted as advocates for their success have been reported as achieving at higher personal and social levels than the general portrait of the medical literature.[1]

Epidemiology edit

Pentasomy X is exceptionally rare. The disorder is estimated to occur in approximately 1 in 250,000 females.[38] Some higher estimates posit the condition may be as frequent as 1 in 85,000, as observed in the related 49,XXXXY syndrome.[21] Fewer than thirty cases of the disorder have been reported in the medical literature, although it is speculated that many more cases have gone undiagnosed.[2] Pentasomy X only occurs in females, as the Y chromosome is in most cases necessary for male sexual development.[5]

History edit

Pentasomy X was first diagnosed in 1963, in a two-year-old girl karyotyped for severe intellectual disability. At the time, four cases of XXXXY syndrome had already been recorded.[39] Pentasomy X was one of the later sex chromosome aneuploidies to be discovered, being preceded by Turner,[40] Klinefelter,[41] and trisomy X[42] in 1959, XXYY syndrome in 1960,[43] and XYY[44] and tetrasomy X[45] in 1961. By the time of Linden, Bender, and Robinson's seminal review of sex chromosome tetrasomy and pentasomy in 1995, only 25 cases had been recorded, the eldest in a girl of 16.[1] As late as 2011, reviews claimed no adult women with pentasomy X had been ascertained,[9] though chromosomal disorder organization Unique noted in 2005 its oldest member with pentasomy X was 29 years old.[3]

See also edit

References edit

  1. ^ a b c d e f g h i j k l m n Linden MG, Bender BG, Robinson A (October 1995). "Sex chromosome tetrasomy and pentasomy". Pediatrics. 96 (4): 672–682. doi:10.1542/peds.96.4.672. PMID 7567329.
  2. ^ a b Demirhan O, Tanriverdi N, Yilmaz MB, Kocaturk-Sel S, Inandiklioglu N, Luleyap U, Akbal E, Comertpay G, Tufan T, Dur O (June 2015). "Report of a new case with pentasomy X and novel clinical findings". Balkan Journal of Medical Genetics. 18 (1): 85–92. doi:10.1515/bjmg-2015-0010. PMC 4768830. PMID 26929910.
  3. ^ a b c d e f g h i j k Unique, Rooman R, Hultén M (2005). "Pentasomy X" (PDF). Unique. Retrieved 7 April 2021.
  4. ^ Patel DR, Cabral MD, Ho A, Merrick J (February 2020). "A clinical primer on intellectual disability". Translational Pediatrics. 9 (1): S23–S35. doi:10.21037/tp.2020.02.02. PMC 7082244. PMID 32206581.
  5. ^ a b c d e f NORD (2020). "Penta X Syndrome". National Organization for Rare Disorders. Retrieved 7 April 2021.
  6. ^ Xiong WY, Jiang ZY, Zou CC (January 2014). "Tetrasomy X in a Child with Multiple Abnormalities: Case Report and Literature Review from China". Hong Kong Journal of Paediatrics. 19 (1): 37–40.
  7. ^ a b c Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L (11 May 2010). "A review of trisomy X (47,XXX)". Orphanet Journal of Rare Diseases. 5 (8): 8. doi:10.1186/1750-1172-5-8. PMC 2883963. PMID 20459843.
  8. ^ Ottesen AM, Aksglaede L, Garn I, Tartaglia N, Tassone F, Gravholt CH, Bojesen A, Sørensen K, Jørgensen N, Rajpert-De Meyts E, Gerdes T, Lind AM, Kjaergaard S, Juul A (May 2010). "Increased number of sex chromosomes affects height in a nonlinear fashion: A study of 305 patients with sex chromosome aneuploidy". American Journal of Medical Genetics Part A. 152A (5): 1206–1212. doi:10.1002/ajmg.a.33334. PMC 5454803. PMID 20425825.
  9. ^ a b c d Schoubben E, Decaestecker K, Quaegebeur K, Danneels L, Mortier G, Cornette L (18 May 2011). "Tetrasomy and pentasomy of the X chromosome". European Journal of Pediatrics. 170 (10): 1325–1327. doi:10.1007/s00431-011-1491-9. PMID 21590264. S2CID 21348257.
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  18. ^ a b Isaacs Cover V (2012). "Trisomy X, Tetrasomy X and Pentasomy X". Living with Klinefelter Syndrome (47,XXY) Trisomy X (47, XXX) and 47, XYY: A Guide for Families and Individuals Affected by Extra X and Y Chromosome Variations. Altona, Manitoba: Friesens. pp. 114–116. ISBN 978-0-615-57400-4.
  19. ^ AXYS, Berry Kravis E (December 2020). "Seizures and Tremor in People with X & Y Chromosome Variations" (PDF). AXYS: Association for X and Y Chromosome Variations. Retrieved 7 April 2021.
  20. ^ Wood A, Kleis L, Toriello H, Cemeroglu AP (17 May 2011). "Mosaic Pentasomy X/Tetrasomy X Syndrome and Premature Ovarian Failure" (PDF). Indian Pediatrics. 48 (5): 402–404. PMID 21654007.
  21. ^ a b c Moraes LM, Cardoso LCA, Moura VLS, Moreira MAM, Menezes AN, Llerena JC, Seuánez HN (7 October 2009). "Detailed analysis of X chromosome inactivation in a 49,XXXXX pentasomy". Molecular Cytogenetics. 2 (20): 20. doi:10.1186/1755-8166-2-20. PMC 2766382. PMID 19811657.
  22. ^ a b Stoicanescu DL, Cevei ML, Gug CR, Simedrea A (10 October 2019). "Multiple anomalies in an adult case with pentasomy X". European Journal of Human Genetics. 27 (2): 1518–1519. doi:10.1038/s41431-019-0494-2. PMC 6876493.
  23. ^ Toussi T, Halal F, Lesage R, Delorme F, Bergeron A (1980). "Renal Hypodysplasia and Unilateral Ovarian Agenesis in the Penta-X Syndrome". American Journal of Medical Genetics. 6 (2): 153–162. doi:10.1002/ajmg.1320060209. PMID 7446561.
  24. ^ Demaliaj E, Cerekja A, Piazze J (16 May 2012). "Sex Chromosome Aneuploidies". Aneuploidy in Health and Disease. Norderstedt: Books on Demand. pp. 123–137. ISBN 9789535106081.
  25. ^ Boeck A, Gfatter R, Braun F, Fritz B (1999). "Pentasomy X and hyper IgE syndrome: co-existence of two distinct genetic disorders". European Journal of Pediatrics. 158 (9): 723–726. doi:10.1007/s004310051187. PMID 10485303. S2CID 24979780.
  26. ^ Myles TD, Burd L, Font G, McCorquodale MM, McCorquodale DJ (October 1995). "Dandy-Walker malformation in a fetus with pentasomy X (49,XXXXX) prenatally diagnosed by fluorescence in situ hybridization technique". Fetal Diagnosis and Therapy. 10 (5): 333–336. doi:10.1159/000264254. PMID 7576173.
  27. ^ Mikwar M, MacFarlane AJ, Marchetti F (4 July 2020). "Mechanisms of oocyte aneuploidy associated with advanced maternal age". Mutation Research/Reviews in Mutation Research. 785: 108320. doi:10.1016/j.mrrev.2020.108320. PMID 32800274. S2CID 221142882.
  28. ^ Arbelaez HEM, Aldana CTS, Bravo NCC, Ospina SY, Mendoza DJF (May 2010). "Análisis clínico y molecular de una pacientecon pentasomia del cromosoma X". Acta Biológica Colombiana (in Spanish). 15 (2): 61–72.
  29. ^ Kuliev A, Verlinsky Y (1 October 2004). "Meiotic and mitotic nondisjunction: lessons from preimplantation genetic diagnosis". Human Reproduction Update. 10 (5): 401–407. doi:10.1093/humupd/dmh036. PMID 15319376.
  30. ^ Chiang T, Schultz RM, Lampson MA (1 January 2012). "Meiotic Origins of Maternal Age-Related Aneuploidy". Biology of Reproduction. 86 (1): 1–7. doi:10.1095/biolreprod.111.094367. PMC 3313661. PMID 21957193.
  31. ^ Pirollo LMA, Salehi LB, Sarta S, Cassone M, Capogna MV, Piccione E, Novelli G, Pietropolli P (29 January 2015). "A New Case of Prenatally Diagnosed Pentasomy X: Review of the Literature". Case Reports in Obstetrics and Gynecology. 2015: 935202. doi:10.1155/2015/935202. PMC 4325205. PMID 25699192.
  32. ^ Dey SK, Ghosh S (29 August 2011). "Etiology of Down Syndrome: Risk of Advanced Maternal Age and Altered Meiotic Recombination for Chromosome 21 Nondisjunction". Genetics and Etiology of Down Syndrome. London: IntechOpen. pp. 23–31. ISBN 978-953-307-631-7.
  33. ^ Bojesen A, Juul S, Gravholt GH (1 February 2003). "Prenatal and Postnatal Prevalence of Klinefelter Syndrome: A National Registry Study". Journal of Clinical Endocrinology & Metabolism. 88 (2): 622–626. doi:10.1210/jc.2002-021491. PMID 12574191.
  34. ^ Abruzzo MA, Hassold TJ (1995). "Etiology of nondisjunction in humans". Environmental and Molecular Mutagenesis. 25 (S2): 38–47. Bibcode:1995EnvMM..25S..38A. doi:10.1002/em.2850250608. PMID 7789361. S2CID 24355576.
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  36. ^ Uno E, Berry D (2012). "X Inactivation and Epigenetics". WEHI. Retrieved 8 April 2021.
  37. ^ O'Connor C (2008). "Chromosomal Abnormalities: Aneuploidies". Nature Education. from the original on 3 November 2020. Retrieved 8 April 2021.
  38. ^ Wilson R, Bennett E, Howell SE, Tartaglia N (20 December 2012). "Sex Chromosome Aneuploidies". Psychopathology of Childhood and Adolescence: A Neuropsychological Approach. New York: Springer Publishing. pp. 596–597. ISBN 978-0826109200.
  39. ^ Kesaree N, Woolley PV, Samson M (December 1963). "A phenotypic female with 49 chromosomes, presumably XXXXX: A case report". The Journal of Pediatrics. 63 (6): 1099–1103. doi:10.1016/s0022-3476(63)80190-0. PMID 14089814.
  40. ^ Ford CE, Jones KW, Polani PE, de Almeida JCC, Briggs JH (1959). "A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome)". Lancet. 273 (7075): 711–713. doi:10.1016/S0140-6736(59)91893-8. PMID 13642858.
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External links edit

April 14, 2024
pentasomy, also, known, xxxxx, chromosomal, disorder, which, female, five, rather, than, copies, chromosome, associated, with, short, stature, intellectual, disability, characteristic, facial, features, heart, defects, skeletal, anomalies, pubertal, reproducti. Pentasomy X also known as 49 XXXXX is a chromosomal disorder in which a female has five rather than two copies of the X chromosome Pentasomy X is associated with short stature intellectual disability characteristic facial features heart defects skeletal anomalies and pubertal and reproductive abnormalities The condition is exceptionally rare with an estimated prevalence between 1 in 85 000 and 1 in 250 000 Pentasomy XOther names49 XXXXXKaryotype of pentasomy XSpecialtyMedical genetics SymptomsIntellectual disability facial dysmorphisms heart defectsUsual onsetConceptionDurationLifelongCausesNondisjunctionDiagnostic methodKaryotypeThe condition has a large variety of symptoms and it is difficult to paint a conclusive portrait of its phenotypes Though significant disability is characteristic there are so few diagnosed cases that confident conclusions about the presentation and prognosis remain impossible Pentasomy X may be mistaken for more common chromosomal disorders such as Down syndrome or Turner syndrome before a conclusive diagnosis is reached Pentasomy X is not inherited but rather occurs via nondisjunction a random event in gamete development In rare cases it may be related to a parent s chromosomal mosaicism The karyotype observed in pentasomy X is formally known as 49 XXXXX which represents the 49 chromosomes observed in the disorder as compared to the 46 in normal human development Contents 1 Presentation 2 Causes 3 Diagnosis 4 Prognosis 5 Epidemiology 6 History 7 See also 8 References 9 External linksPresentation editThe major clinical features of pentasomy X are intellectual disability short stature facial and musculoskeletal abnormalities and congenital heart defects 1 Although one recorded case has been of low average intelligence 2 all other known cases have been intellectually disabled with an average IQ of 50 1 The overall portrait is one of moderate intellectual disability 3 defined by an adult cognitive capacity similar to that of a six to eight year old and the ability to acquire basic living and employment skills with support 4 Some girls with pentasomy X attend special education in mainstream schools through mainstreaming or inclusion while some attend special schools 3 nbsp A 15 year old girl with pentasomy X demonstrating facial limb and skeletal featuresPentasomy X is associated with a number of physical anomalies including short stature clinodactyly incurved pinky fingers and distinctive facial features Common findings include microcephaly low set ears hypertelorism wide spaced eyes and epicanthic folds 5 The characteristic facies have been described as coarse 1 much like those of the related disorder tetrasomy X 6 Pentasomy X is unique amongst X chromosome polysomies for its association with short stature when most related disorders are associated with tall stature 7 the average height in pentasomy X is one standard deviation below the norm 8 Hypotonia often severe is a frequent finding as are related musculoskeletal issues such as hip dysplasia 9 The severity of repeated joint dislocations may lead to a differential diagnosis of Larsen syndrome as suggested in one reported case 10 Bone maturation may be delayed 11 Another skeletal finding is taurodontism where the pulp of the teeth is enlarged into the roots 5 other dental abnormalities such as missing teeth and severe tooth decay have also been reported 12 These findings are not specific to pentasomy X but rather common to sex chromosome aneuploidies in general and in particular show a strong resemblance to the male counterpart 49 XXXXY 13 Epicanthic folds and hypertelorism are also observed in tetrasomy and trisomy X 7 while clinodactyly and radioulnar synostosis are seen in all sex chromosome aneuploidies 1 14 15 and taurodontism is specifically common to X chromosome polysomies 16 Heart defects are associated with the syndrome Pentasomy X has one of the highest rates of congenital heart defects of any chromosomal disorder with 56 5 of recorded patients having a heart defect of some kind Patent ductus arteriosus is particularly frequent 3 17 The majority of such conditions resolve without surgical treatment although a minority require it 3 Ventricular septal defects are also frequent 1 Other internal medical issues frequently recorded include kidney and urinary defects 3 Epilepsy has been associated with the condition 18 though seems to be rare 3 In sex chromosome aneuploidies as a whole epilepsy is usually mild and amenable to treatment 19 and reports of epilepsy in pentasomy X have described it resolving with treatment and allowing antiepileptic drugs to eventually be stopped 3 Puberty is altered in pentasomy X although as few adults with the condition have been reported the full scope of such alterations is unclear In the sister condition of tetrasomy X half of all women undergo puberty normally while half have no or incomplete puberty 1 Some adolescents and adults with pentasomy X have been prepubertal 1 while some have had premature ovarian failure early menopause 20 and some have had apparently non noteworthy pubertal development 21 22 Though external genitalia is generally normal underlying gonadal dysfunction is frequent including ovarian dysfunction or an unusually small uterus 17 No cases are known of women with pentasomy X having children but although fertility is likely reduced some may be able to 23 Little is understood about the psychological and behavioural phenotype of pentasomy X Girls and women with the disorder are frequently described as shy and cooperative 1 Such traits are common to other conditions involving extra copies of the X chromosome 15 24 Developmental delays can cause difficulty communicating resulting in frustration and tantrums Overall the syndrome is not associated with severe behavioural issues 3 A number of disorders have been reported as comorbid with sex chromosome aneuploidies including pentasomy X In one case report pentasomy X occurred alongside the similarly rare hyperimmunoglobulin E syndrome 25 Other possibly coincidental associations have included cerebral palsy 22 and Dandy Walker malformation 26 Causes edit nbsp Maternal age in 21 cases of pentasomy X showing the unclear relationshipPentasomy X is caused by nondisjunction a process through which gametes eggs or sperm with too many or too few chromosomes are produced In nondisjunction homologous chromosomes or sister chromatids fail to separate properly when producing gametes 27 In sex chromosome tetrasomy and pentasomy the extra chromosomes are consistently inherited from one parent 1 In the specific case of pentasomy X all known cases have inherited the additional chromosomes from the mother This has been suggested to relate to genomic imprinting specifically it is hypothesized that specific loci on the sex chromosomes are affected by imprinting such that only maternal overimprinting is survivable and cases of pentasomy X where the additional chromosomes were inherited from the father would be incompatible with life 28 As well as during gamete development nondisjunction can occur after conception resulting in a mosaic karyotype 29 Nondisjunction is related to advanced maternal age 30 although due to its rarity the maternal age effect in pentasomy X is unclear 31 More common aneuploidy syndromes such as Down syndrome and Klinefelter s syndrome have strong relationships with maternal age 32 33 Pentasomy X is not inherited 5 and is not caused by the actions of the parents 34 However in rare cases pentasomy X may be related to chromosomal mosaicism in a parent 3 35 X inactivation is a major factor in pentasomy X X inactivation is the process through which genes in second or higher copies of the X chromosome are turned off such that any cell has only one active copy of the chromosome 36 However X inactivation appears to be disrupted in pentasomy X allowing up to half of the supposedly inactive genetic material to actually work This is assumed to contribute to the severe phenotype of the condition compared to other sex chromosome aneuploidies 21 Diagnosis editChromosome aneuploidies such as pentasomy X are diagnosed through the process of karyotyping or chromosome testing 37 Diagnosis cannot be made on the basis of phenotype alone as multiple other conditions present similarly 1 The phenotype of pentasomy X is not specific to the disorder and many other conditions can be differential diagnoses One is tetrasomy X a related disorder in which a girl or woman has four copies of the X chromosome The general profiles of the conditions are similar with developmental delays mild dysmorphic features and shared congenital anomalies such as clinodactyly and radioulnar synostosis However the phenotype of pentasomy X is more severe than that of tetrasomy X with lower IQ and more severe dysmorphism Pentasomy X also has additional characteristics uncommon in the tetrasomy such as short stature 1 7 Mosaic karyotypes with both 48 XXXX and 49 XXXXX cells are also possible Though very few mosaic cases have been reported the phenotype appears intermediate in severity between tetrasomy and pentasomy X 9 Another potential differential diagnosis is Down syndrome The features of the two conditions overlap and some girls with pentasomy X may be assumed to have Down s before genetic ascertainment 5 Some cases of pentasomy X have had family histories of Down syndrome inciting speculation that the conditions may tend to recur in the same family lines alternatively it may suggest that some patients diagnosed with Down syndrome on the basis of phenotype may actually have pentasomy X 17 The phenotype of pentasomy X has also been compared to that of Turner syndrome characterized by a female having one copy of the X chromosome Both Turner s and pentasomy X are female only disorders characterized by short stature heart defects and abnormal pubertal development However the intellectual disabilities observed in pentasomy X are rare in Turner syndrome 5 Prognosis editThe long term prognosis of pentasomy X is unclear due to its low prevalence 1 Though some reviews claim a poor prognosis due to the congenital defects observed in severe cases 9 support groups report milder abnormalities than common in the medical literature including adults with pentasomy X in fair health 3 The spectrum of severity varies long term support is consistent though some women have been reported as being able to work part time and manage some of their affairs 18 For sex chromosome tetrasomy and pentasomy disorders as a whole good prognosis is linked to strong parental and personal support Girls and women with pentasomy X whose caregivers have acted as advocates for their success have been reported as achieving at higher personal and social levels than the general portrait of the medical literature 1 Epidemiology editPentasomy X is exceptionally rare The disorder is estimated to occur in approximately 1 in 250 000 females 38 Some higher estimates posit the condition may be as frequent as 1 in 85 000 as observed in the related 49 XXXXY syndrome 21 Fewer than thirty cases of the disorder have been reported in the medical literature although it is speculated that many more cases have gone undiagnosed 2 Pentasomy X only occurs in females as the Y chromosome is in most cases necessary for male sexual development 5 History editPentasomy X was first diagnosed in 1963 in a two year old girl karyotyped for severe intellectual disability At the time four cases of XXXXY syndrome had already been recorded 39 Pentasomy X was one of the later sex chromosome aneuploidies to be discovered being preceded by Turner 40 Klinefelter 41 and trisomy X 42 in 1959 XXYY syndrome in 1960 43 and XYY 44 and tetrasomy X 45 in 1961 By the time of Linden Bender and Robinson s seminal review of sex chromosome tetrasomy and pentasomy in 1995 only 25 cases had been recorded the eldest in a girl of 16 1 As late as 2011 reviews claimed no adult women with pentasomy X had been ascertained 9 though chromosomal disorder organization Unique noted in 2005 its oldest member with pentasomy X was 29 years old 3 See also editTrisomy X Skewed X inactivationReferences edit a b c d e f g h i j k l m n Linden MG Bender BG Robinson A October 1995 Sex chromosome tetrasomy and pentasomy Pediatrics 96 4 672 682 doi 10 1542 peds 96 4 672 PMID 7567329 a b Demirhan O Tanriverdi N Yilmaz MB Kocaturk Sel S Inandiklioglu N Luleyap U Akbal E Comertpay G Tufan T Dur O June 2015 Report of a new case with pentasomy X and novel clinical findings Balkan Journal of Medical Genetics 18 1 85 92 doi 10 1515 bjmg 2015 0010 PMC 4768830 PMID 26929910 a b c d e f g h i j k Unique Rooman R Hulten M 2005 Pentasomy X PDF Unique Retrieved 7 April 2021 Patel DR Cabral MD Ho A Merrick J February 2020 A clinical primer on intellectual disability Translational Pediatrics 9 1 S23 S35 doi 10 21037 tp 2020 02 02 PMC 7082244 PMID 32206581 a b c d e f NORD 2020 Penta X Syndrome National Organization for Rare Disorders Retrieved 7 April 2021 Xiong WY Jiang ZY Zou CC January 2014 Tetrasomy X in a Child with Multiple Abnormalities Case Report and Literature Review from China Hong Kong Journal of Paediatrics 19 1 37 40 a b c Tartaglia NR Howell S Sutherland A Wilson R Wilson L 11 May 2010 A review of trisomy X 47 XXX Orphanet Journal of Rare Diseases 5 8 8 doi 10 1186 1750 1172 5 8 PMC 2883963 PMID 20459843 Ottesen AM Aksglaede L Garn I Tartaglia N Tassone F Gravholt CH Bojesen A Sorensen K Jorgensen N Rajpert De Meyts E Gerdes T Lind AM Kjaergaard S Juul A May 2010 Increased number of sex chromosomes affects height in a nonlinear fashion A study of 305 patients with sex chromosome aneuploidy American Journal of Medical Genetics Part A 152A 5 1206 1212 doi 10 1002 ajmg a 33334 PMC 5454803 PMID 20425825 a b c d Schoubben E Decaestecker K Quaegebeur K Danneels L Mortier G Cornette L 18 May 2011 Tetrasomy and pentasomy of the X chromosome European Journal of Pediatrics 170 10 1325 1327 doi 10 1007 s00431 011 1491 9 PMID 21590264 S2CID 21348257 Dryer RF Patil SR Zellweger HU Simpson JM Hanson JW Aschenbrenner C Weinstein SL 1979 Pentasomy X with multiple dislocations American Journal of Medical Genetics 4 4 313 321 doi 10 1002 ajmg 1320040402 PMID 539601 Archidiacono N Rocchi M Valente M Filipi G November 1979 X pentasomy A case and review Human Genetics 52 1 66 77 doi 10 1007 bf00284599 PMID 527976 S2CID 29475412 Alves NS Assaf AV Martins AM Rodrigues Cajazeira MR Antunes LS Silveira FM 2015 Dental care for an adolescent with chromosome pentasomy rare case report with a two year follow up Revista Gaucha de Odontologia 63 4 507 511 doi 10 1590 1981 863720150003000223052 Sergovich F Uilenberg C Pozsonyi J 1971 The 49 XXXXX chromosome constitution Similarities to the 49 XXXXY condition The Journal of Pediatrics 2 78 285 290 doi 10 1016 s0022 3476 71 80013 6 PMID 5539772 Lenroot RK Lee NR Giedd JN 2009 Effects of Sex Chromosome Aneuploidies on Brain Development Evidence From Neuroimaging Studies Developmental Disabilities Research Reviews 15 4 318 327 doi 10 1002 ddrr 86 PMC 2996824 PMID 20014372 a b Visootsak J Graham JM 24 October 2006 Klinefelter syndrome and other sex chromosomal aneuploidies Orphanet Journal of Rare Diseases 1 1 42 doi 10 1186 1750 1172 1 42 PMC 1634840 PMID 17062147 Tartaglia N Howell S Wilson R Janusz J Boada R Martin S Frazier JB Pfeiffer M Regan K McSwegin S Zeitler P 17 July 2015 The eXtraordinarY Kids Clinic an interdisciplinary model of care for children and adolescents with sex chromosome aneuploidy Journal of Multidisciplinary Healthcare 8 1 323 334 doi 10 2147 JMDH S80242 PMC 4514383 PMID 26229481 a b c Kassai R Hamanda I Furuta H Cho K Abe K Deng HX Niikawa N 1991 Penta X Syndrome A Case Report With Review of the Literature American Journal of Medical Genetics 40 1 51 56 doi 10 1002 ajmg 1320400110 PMID 1887850 a b Isaacs Cover V 2012 Trisomy X Tetrasomy X and Pentasomy X Living with Klinefelter Syndrome 47 XXY Trisomy X 47 XXX and 47 XYY A Guide for Families and Individuals Affected by Extra X and Y Chromosome Variations Altona Manitoba Friesens pp 114 116 ISBN 978 0 615 57400 4 AXYS Berry Kravis E December 2020 Seizures and Tremor in People with X amp Y Chromosome Variations PDF AXYS Association for X and Y Chromosome Variations Retrieved 7 April 2021 Wood A Kleis L Toriello H Cemeroglu AP 17 May 2011 Mosaic Pentasomy X Tetrasomy X Syndrome and Premature Ovarian Failure PDF Indian Pediatrics 48 5 402 404 PMID 21654007 a b c Moraes LM Cardoso LCA Moura VLS Moreira MAM Menezes AN Llerena JC Seuanez HN 7 October 2009 Detailed analysis of X chromosome inactivation in a 49 XXXXX pentasomy Molecular Cytogenetics 2 20 20 doi 10 1186 1755 8166 2 20 PMC 2766382 PMID 19811657 a b Stoicanescu DL Cevei ML Gug CR Simedrea A 10 October 2019 Multiple anomalies in an adult case with pentasomy X European Journal of Human Genetics 27 2 1518 1519 doi 10 1038 s41431 019 0494 2 PMC 6876493 Toussi T Halal F Lesage R Delorme F Bergeron A 1980 Renal Hypodysplasia and Unilateral Ovarian Agenesis in the Penta X Syndrome American Journal of Medical Genetics 6 2 153 162 doi 10 1002 ajmg 1320060209 PMID 7446561 Demaliaj E Cerekja A Piazze J 16 May 2012 Sex Chromosome Aneuploidies Aneuploidy in Health and Disease Norderstedt Books on Demand pp 123 137 ISBN 9789535106081 Boeck A Gfatter R Braun F Fritz B 1999 Pentasomy X and hyper IgE syndrome co existence of two distinct genetic disorders European Journal of Pediatrics 158 9 723 726 doi 10 1007 s004310051187 PMID 10485303 S2CID 24979780 Myles TD Burd L Font G McCorquodale MM McCorquodale DJ October 1995 Dandy Walker malformation in a fetus with pentasomy X 49 XXXXX prenatally diagnosed by fluorescence in situ hybridization technique Fetal Diagnosis and Therapy 10 5 333 336 doi 10 1159 000264254 PMID 7576173 Mikwar M MacFarlane AJ Marchetti F 4 July 2020 Mechanisms of oocyte aneuploidy associated with advanced maternal age Mutation Research Reviews in Mutation Research 785 108320 doi 10 1016 j mrrev 2020 108320 PMID 32800274 S2CID 221142882 Arbelaez HEM Aldana CTS Bravo NCC Ospina SY Mendoza DJF May 2010 Analisis clinico y molecular de una pacientecon pentasomia del cromosoma X Acta Biologica Colombiana in Spanish 15 2 61 72 Kuliev A Verlinsky Y 1 October 2004 Meiotic and mitotic nondisjunction lessons from preimplantation genetic diagnosis Human Reproduction Update 10 5 401 407 doi 10 1093 humupd dmh036 PMID 15319376 Chiang T Schultz RM Lampson MA 1 January 2012 Meiotic Origins of Maternal Age Related Aneuploidy Biology of Reproduction 86 1 1 7 doi 10 1095 biolreprod 111 094367 PMC 3313661 PMID 21957193 Pirollo LMA Salehi LB Sarta S Cassone M Capogna MV Piccione E Novelli G Pietropolli P 29 January 2015 A New Case of Prenatally Diagnosed Pentasomy X Review of the Literature Case Reports in Obstetrics and Gynecology 2015 935202 doi 10 1155 2015 935202 PMC 4325205 PMID 25699192 Dey SK Ghosh S 29 August 2011 Etiology of Down Syndrome Risk of Advanced Maternal Age and Altered Meiotic Recombination for Chromosome 21 Nondisjunction Genetics and Etiology of Down Syndrome London IntechOpen pp 23 31 ISBN 978 953 307 631 7 Bojesen A Juul S Gravholt GH 1 February 2003 Prenatal and Postnatal Prevalence of Klinefelter Syndrome A National Registry Study Journal of Clinical Endocrinology amp Metabolism 88 2 622 626 doi 10 1210 jc 2002 021491 PMID 12574191 Abruzzo MA Hassold TJ 1995 Etiology of nondisjunction in humans Environmental and Molecular Mutagenesis 25 S2 38 47 Bibcode 1995EnvMM 25S 38A doi 10 1002 em 2850250608 PMID 7789361 S2CID 24355576 Muneer RS Stone JR Stupca PJ Kamat SB Thompson LM Rennart OM 1 April 1981 A penta X female 49 XXXXX a result of parental mosaicism Pediatric Research 15 556 1981 doi 10 1203 00006450 198104001 00768 Uno E Berry D 2012 X Inactivation and Epigenetics WEHI Retrieved 8 April 2021 O Connor C 2008 Chromosomal Abnormalities Aneuploidies Nature Education Archived from the original on 3 November 2020 Retrieved 8 April 2021 Wilson R Bennett E Howell SE Tartaglia N 20 December 2012 Sex Chromosome Aneuploidies Psychopathology of Childhood and Adolescence A Neuropsychological Approach New York Springer Publishing pp 596 597 ISBN 978 0826109200 Kesaree N Woolley PV Samson M December 1963 A phenotypic female with 49 chromosomes presumably XXXXX A case report The Journal of Pediatrics 63 6 1099 1103 doi 10 1016 s0022 3476 63 80190 0 PMID 14089814 Ford CE Jones KW Polani PE de Almeida JCC Briggs JH 1959 A sex chromosome anomaly in a case of gonadal dysgenesis Turner s syndrome Lancet 273 7075 711 713 doi 10 1016 S0140 6736 59 91893 8 PMID 13642858 Jacobs PA Strong JA 31 January 1959 A case of human intersexuality having a possible XXY sex determining mechanism Nature 183 4657 302 303 Bibcode 1959Natur 183 302J doi 10 1038 183302a0 PMID 13632697 S2CID 38349997 Jacobs PA Baikie AG Court Brown WM MacGregor TN Harnden DG 26 September 1959 Evidence for the existence of the human super female Lancet 274 7100 423 425 doi 10 1016 S0140 6736 59 90415 5 PMID 14406377 Muldal S Ockey CH 27 August 1960 The double male a new chromosome constitution in Klinefelter s syndrome Lancet 276 7147 492 493 doi 10 1016 S0140 6736 60 91624 X Sandberg AA Koepf GF Ishihara T Hauschka TS 26 August 1961 An XYY human male Lancet 278 7200 488 489 doi 10 1016 S0140 6736 61 92459 X PMID 13746118 Carr DH Barr ML Plunkett ER 21 January 1961 An XXXX sex chromosome complex in two mentally defective females Canadian Medical Association Journal 84 3 131 137 PMC 1939166 PMID 13690988 External links edit Retrieved from https en wikipedia org w index php title Pentasomy X amp oldid 1216434384, wikipedia, wiki, book, books, library,

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