49,XXXXYxxc syndrome | |
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Other names | Fraccaro syndrome |
A 19-year-old man with XXXXY syndrome and prognathism | |
Specialty | Medical genetics |
Usual onset | Prenatal |
Duration | Lifelong |
Causes | Cellular nondisjunction during meiosis |
Diagnostic method | Karyotype |
Frequency | 1 in 85,000 to 100,000 |
49,XXXXY syndrome is an extremely rare aneuploidic sex chromosomal abnormality. It occurs in approximately 1 out of 85,000 to 100,000 males. This syndrome is the result of maternal non-disjunction during both meiosis I and II. It was first diagnosed in 1960 and was coined Fraccaro syndrome after the researcher.
Signs and symptoms
The symptoms of 49,XXXXY are slightly similar to those of Klinefelter syndrome and 48,XXXY, but they are usually much more severe. Aneuploidy is often fatal, but there is "X-inactivation", where the effect of the additional gene dosage due to the presence of extra X chromosomes is greatly reduced.
Reproductive
Those with 49,XXXXY syndrome tend to exhibit infantile secondary sex characteristics with sterility in adulthood.
- Hypoplastic genitalia
- Absent or delayed puberty
Physical
Males with 49,XXXXY tend to have numerous skeletal anomalies. These skeletal anomalies include:
- Genu valgum
- Pes cavus
- Fifth finger clinodactyly
The effects also include:
- Cleft palate
- Club feet
- Respiratory conditions
- Short or/and broad neck
- Low birth weight
- Hyperextensible joints
- Short stature
- Narrow shoulders
- Coarse features in older age
- Hypertelorism
- Epicanthal folds
- Prognathism
- Gynecomastia (rare)
- Muscular hypotonia
- Cryptorchidism
- Congenital heart defects
- A very round face in infancy
49,XXXXY may also be associated with increased rates of primary immunodeficiency.
Cognitive and developmental
Much like Down syndrome, the mental effects of 49,XXXXY syndrome vary. Impaired speech and maladaptive behavioral problems are typical. One study looked at males that were diagnosed with 48,XXYY, 48,XXXY and 49,XXXXY. They found that males with 48,XXXY and 49,XXXXY function at a much lower cognitive level than males their age. These males also tend to exhibit more immature behavior for their chronological age; increased aggressive tendencies were also cited in this study.
A 2020 study found that boys with 49,XXXXY have heightened rates of internalizing behavior and anxiety, beginning as early as preschool. Tests using the Social Responsiveness Scale-2 (SRS-2) found that while those with the condition generally showed more signs of social impairment, there was minimal effect on their social awareness.
Pathophysiology
As its name indicates, a person with the syndrome has one Y chromosome and four X chromosomes on the 23rd pair, thus having forty-nine chromosomes rather than the normal forty-six. As with most categories of aneuploidy disorders, 49,XXXXY syndrome is often accompanied by intellectual disability. It can be considered a form or variant of Klinefelter syndrome (47,XXY). Individuals with this syndrome are typically mosaic, being 49,XXXXY/48, XXXX.
It is genetic but not hereditary, meaning that while the genes of the parents cause the syndrome, there is a small chance of more than one child having the syndrome. The probability of inheriting the disease is about one percent.
Diagnosis
49,XXXXY can be clinically diagnosed through karyotyping. Facial dysmorphia and other somatic abnormalities may be reason to have the genetic testing done.
Treatment
While there is no treatment to correct the genetic abnormality of this syndrome, there is the potential to treat the symptoms. As a result of infertility, one man from Iran used artificial reproductive methods. An infant in Iran diagnosed with 49,XXXXY syndrome was born with patent ductus arteriosus, which was corrected with surgery, and other complications that were managed with replacement therapy.
The administration of testosterone therapy has been shown to improve motor skills, speech, and nonverbal IQ in males with 49,XXXXY.
See also
- Sex chromosome anomalies
- Aneuploidy
- Turner syndrome
- Klinefelter syndrome
- 49, XXXXX, a similar syndrome that affects females
References
- Visootsak J, Graham JM (2006). "Klinefelter syndrome and other sex chromosomal aneuploidies". Orphanet J Rare Dis. 1: 42. doi:10.1186/1750-1172-1-42. PMC 1634840. PMID 17062147.
- ^ Fraccaro, M.; Kaijser, K.; Lindsten, J. (1960-10-22). "A child with 49 chromosomes". Lancet. 2 (7156): 899–902. doi:10.1016/s0140-6736(60)91963-2. ISSN 0140-6736. PMID 13701146.
- Etemadi, Katayoon; Basir, Behnaz; Ghahremani, Safieh (March 2015). "Neonatal diagnosis of 49, XXXXY syndrome". Iranian Journal of Reproductive Medicine. 13 (3): 181–184. ISSN 1680-6433. PMC 4426158. PMID 26000009.
- ^ Hadipour, Fatemeh; Shafeghati, Yousef; Bagherizadeh, Eiman; Behjati, Farkhondeh; Hadipour, Zahra (2013). "Fraccaro syndrome: report of two Iranian cases: an infant and an adult in a family". Acta Medica Iranica. 51 (12): 907–909. ISSN 1735-9694. PMID 24442548.
- ^ Webspawner.com article on 49,XXXXY syndrome Archived 2008-09-14 at the Wayback Machine. Retrieved 26 March 2008.
- Hammami, Mohammad Bakri; Elkhapery, Ahmed (2020-07-29). "Sexual and developmental aspects of 49, XXXXY Syndrome: A case report". Andrologia. 52 (10): e13771. doi:10.1111/and.13771. PMID 32725928 – via Wiley Online Database.
- Sprouse, Courtney; Tosi, Laura; Stapleton, Emily; Gropman, Andrea L.; Mitchell, Francie L.; Peret, Rick; Sadeghin, Teresa; Haskell, Kathryn; Samango-Sprouse, Carole A. (2013). "Musculoskeletal anomalies in a large cohort of boys with 49, XXXXY". American Journal of Medical Genetics. 163 (1): 44–49. doi:10.1002/ajmg.c.31354. PMID 23359596. S2CID 40989726.
- Keller, Michael D.; Sadeghin, Teresa; Samango-Sprouse, Carole; Orange, Jordan S. (2013-01-23). "Immunodeficiency in patients with 49,XXXXY chromosomal variation". American Journal of Medical Genetics. 163 (1): 50–54. doi:10.1002/ajmg.c.31348. PMC 4886306. PMID 23345259 – via Wiley Online Database.
- ^ Visootsak J, Rosner B, Dykens E, Tartaglia N, Graham JM (June 2007). "Behavioral phenotype of sex chromosome aneuploidies: 48,XXYY, 48,XXXY, and 49,XXXXY". Am. J. Med. Genet. A. 143A (11): 1198–203. doi:10.1002/ajmg.a.31746. PMID 17497714. S2CID 25732790.
- ^ Lasutschinkow, Patricia C.; Gropman, Andrea L.; Porter, Grace F.; Sadeghin, Teresa; Samango-Sprouse, Carole A. (2020-02-21). "Behavioral phenotype of 49,XXXXY syndrome: Presence of anxiety-related symptoms and intact social awareness". American Journal of Medical Genetics. 182 (5): 974–986. doi:10.1002/ajmg.a.61507. PMID 32083381. S2CID 211230717 – via Wiley Online Database.
- Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 179. ISBN 0-7216-0187-1.
- Blumenthal, Jonathan D.; Baker, Eva H.; Lee, Nancy Raitano; Wade, Benjamin; Clasen, Liv S.; Lenroot, Rhoshel K.; Giedd, Jay N. (2013). "Brain morphological abnormalities in 49,XXXXY syndrome: A pediatric magnetic resonance imaging study". NeuroImage: Clinical. 2: 197–203. doi:10.1016/j.nicl.2013.01.003. PMC 3649771. PMID 23667827.
- Tosi, Laura; Mitchell, Francie; Porter, Grace F.; Ruland, Leigh; Gropman, Andrea; Lasutschinkow, Patricia C.; Tran, Selena L.; Rajah, Elmer N.; Gillies, Austin P.; Hendrie, Patricia; Peret, Rick; Sadeghin, Teresa; Samango-Sprouse, Carole A. (2020-04-03). "Musculoskeletal abnormalities in a large international cohort of boys with 49,XXXXY". American Journal of Medical Genetics. 185 (12): 3531–3540. doi:10.1002/ajmg.a.61578. PMID 32243688. S2CID 214785617 – via Wiley Online Database.
Further reading
- Jonathan D. Blumenthal; Eva H. Baker; Nancy Raitano Lee; Benjamin Wade; Liv S. Clasen; Rhoshel K. Lenroot; Jay N. Giedd (2013). "Brain morphological abnormalities in 49,XXXXY syndrome: A pediatric magnetic resonance imaging study". NeuroImage: Clinical. 2: 197–203. doi:10.1016/j.nicl.2013.01.003. PMC 3649771. PMID 23667827.
External links
Classification | D |
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