XXXXY syndrome
| 49,XXXXY syndrome | |
|---|---|
| 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.[1][2][3] This syndrome is the result of maternal non-disjunction during both meiosis I and II.[4] It was first diagnosed in 1960 and was coined Fraccaro syndrome after the researcher.[2]
Signs and symptoms[edit]
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.[5]
Reproductive[edit]
Those with 49,XXXXY syndrome tend to exhibit infantile secondary sex characteristics with sterility in adulthood.[5]
- Hypoplastic genitalia[5]
- Absent or delayed puberty[6]
Physical[edit]
Males with 49,XXXXY tend to have numerous skeletal anomalies. These skeletal anomalies include:[7]
- 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[5]
49,XXXXY may also be associated with increased rates of primary immunodeficiency.[8]
Cognitive and developmental[edit]
Much like Down syndrome, the mental effects of 49,XXXXY syndrome vary. Impaired speech and maladaptive behavioral problems are typical.[9] 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.[9]
A 2020 study found that boys with 49,XXXXY have heightened rates of internalizing behavior and anxiety, beginning as early as preschool.[10] 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.[10]
Pathophysiology[edit]
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).[11] Individuals with this syndrome are typically mosaic, being 49,XXXXY/48, XXXX.[4]
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.[5]
Diagnosis[edit]
49,XXXXY can be clinically diagnosed through karyotyping.[12] Facial dysmorphia and other somatic abnormalities may be reason to have the genetic testing done.[4]
Treatment[edit]
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.[4] 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.[4]
The administration of testosterone therapy has been shown to improve motor skills, speech, and nonverbal IQ in males with 49,XXXXY.[13]
See also[edit]
- Aneuploidy
- Turner syndrome
- Klinefelter syndrome
- 49, XXXXX, a similar syndrome that affects females
References[edit]
- ^ 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.
- ^ a b 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.
- ^ a b c d e 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.
- ^ a b c d e 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.
- ^ a b 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.
- ^ a b 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[edit]
- 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.