Diseases Studied

Also known as 45,X; Monosomy X; Mosaic Turner Syndrome

Turner syndrome (TS) is a sex chromosome aneuploidy affecting approximately 1 in 2,000-2,5000 girls, caused by the complete or partial absence of a second X chromosome. Symptoms of Turner syndrome often include short stature, congenital heart defects, kidney malformations, ovarian failure, infertility, as well as increased risks for autoimmune and metabolic disorders, hearing loss, learning disabilities, and social or behavioral challenges. While 45,X, also known as monosomy X (when the entire X chromosome is missing) is the most common genetic finding in Turner syndrome, other karyotypes are possible, such as structural abnormalities in the second X chromosome or mosaicism resulting in multiple cell lines in a single person. 

Also known as Triple X;47,XXX

Trisomy X syndrome is a sex chromosome aneuploidy characterized by the presence of an additional X chromosome in females. Women and girls with Trisomy X may have tall stature, low muscle tone, and risks for neurodevelopmental disorders including developmental delays (especially regarding expressive language), learning disabilities, ADHD, autism and anxiety. The presence and severity of symptoms widely vary between individuals, with some girls having few symptoms while others are more significantly affected. While Trisomy X affects approximately 1 in 1000 girls, many go their entire lives without being diagnosed. The onset of prenatal cell-free DNA screening has increased the identification of Trisomy X in newborns and active research is being done to redefine the natural history of this condition when identified at birth.

Also known as 47,XXY

Klinefelter syndrome is a sex chromosome aneuploidy characterized by the presence of an additional X chromosome in males. Men and boys with XXY often have tall stature, testicular dysfunction resulting in testosterone deficiency and infertility, low muscle tone, risk for gynecomastia, and risks for neurodevelopmental disorders including developmental delays (especially regarding expressive language), learning disabilities, ADHD, anxiety, and social difficulties. The presence and severity of these symptoms are highly variable between individuals, with some boys having few symptoms while others are more significantly affected. While nonmosaic XXY affects about 1 in 650-820 boys, there are also forms of mosaic XXY, such as XXY/XY or XXY/XXYY, which can occur. Many men with XXY may not be diagnosed until adulthood during infertility evaluations or never know they have XXY their entire lives. The onset of prenatal cell-free DNA screening has increased the identification of XXY in newborns and active research is being done to redefine the natural history of this condition when identified at birth.

Also known as 47,XYY; Jacobs syndrome; Double Y syndrome

XYY syndrome is a sex chromosome aneuploidy characterized by the presence of an additional Y chromosome in males. Men and boys with XYY often have tall stature, low muscle tone, and risks for neurodevelopmental disorders including developmental delays (especially regarding expressive language), learning disabilities, ADHD, autism and anxiety. The presence and severity of these symptoms widely vary between individuals, with some boys having few symptoms while others are more significantly affected. While XYY affects approximately 1 in 1,000 boys, many men go their entire lives without being diagnosed. The onset of prenatal cell-free DNA screening has increased the identification of XYY in newborns and active research is hoping to redefine the natural history of this condition when identified at birth.

Also known as 48,XXYY

XXYY syndrome is a sex chromosome aneuploidy characterized by the presence of an additional X chromosome and an additional Y chromosome in males. Though previously considered a variant of XXY or Klinefelter syndrome, XXYY is now recognized as a distinct condition with its own unique description and associated symptoms. Men and boys with XXYY often have tall stature, testicular dysfunction resulting in testosterone deficiency and infertility, low muscle tone, and higher risks for neurodevelopmental disorders including developmental delays (especially regarding expressive language), learning and intellectual disabilities, ADHD, autism and anxiety, as well as other congenital malformations and medical problems. This karyotype is rarer, affecting approximately 1 in 18,000-40,000 males.

Also known as 48,XYYY or X-Triple Y syndrome

XYYY syndrome is an extremely rare sex chromosome aneuploidy characterized by the presence of one X chromosome and three Y chromosomes (total 48 chromosomes). Its prevalence is exceedingly low, with only a handful of postnatal cases reported in medical literature. The clinical phenotype of 48,XYYY syndrome is not well established due to case reports in literature, but available reports suggest that affected individuals may present with subtle dysmorphic features, relative height deficiency, and may require growth hormone therapy. There is also evidence of immune cell population differences and deregulation of genes associated with hematological malignancies, which may warrant long-term hemato-oncological surveillance. Most cases described are mosaic, such as 45,X/48,XYYY, further complicating phenotype characterization and prevalence estimates.

Also known as 48,XXXY

XXXY syndrome is a rare sex chromosome aneuploidy in males characterized by the presence of two extra X chromosomes (total karyotype: 48,XXXY). Symptoms include congenital anomalies, tall stature, testicular dysfunction, infertility, and neurodevelopmental disorders including developmental delays (especially regarding expressive language), learning and intellectual disabilities, ADHD, autism, anxiety, and behavior problems. It is estimated that 1 in 17,000- 50,000 boys have XXXY syndrome.

Also known as tetrasomy X or 48,XXXX

XXXX syndrome is a rare sex chromosome aneuploidy in females characterized by the presence of four X chromosomes in each cell, leading to variable neurodevelopmental symptoms including intellectual disability, speech and language disorders, executive dysfunction, and physical features such as low muscle tone and primary ovarian failure.

Also known as 49,XXXXY

XXXXY syndrome is a rare sex chromosome aneuploidy in males characterized by congenital abnormalities (including heart and skeletal defects), intellectual disability, developmental delays, distinctive facial features, musculoskeletal abnormalities, and hypogonadism. Common symptoms include speech and language impairment, low muscle tone, short stature, musculoskeletal radioulnar synostosis, and genital anomalies, such as micropenis and undescended testes. Behavioral issues, including anxiety and irritability, are also frequently observed. It is one of the rarest sex chromosome aneuploidies, estimated to affect approximately 1 in 85,000-100,000 males.

Also known as 49,XXXYY or "3X 2Y syndrome"

XXXYY syndrome is an extremely rare sex chromosome aneuploidy in males characterized by the presence of 3 X chromosomes and 2 Y chromosomes. There are very few cases reported in medical literature. Symptoms described include congenital and musculoskeletal abnormalities (including hips and forearms), developmental delays, intellectual disability, facial features, hypogonadism, genital abnormalities (micropenis and undescended testicles), and tremor.

Also known as 49,XXYYY or "2X 3Y syndrome"

XXYYY syndrome is an extremely rare sex chromosome aneuploidy characterized by the presence of two extra Y chromosomes and one extra X chromosome in males, resulting in a total of 49 chromosomes. There are very few cases reported in medical literature. Symptoms described include musculoskeletal abnormalities, genital abnormalities (micropenis, small undescended testicles), low muscle tone, tall stature, intellectual disability, developmental delays and behavior problems.

Also known as 49,XYYYY or "X-4-Y"

XYYYY syndrome is an extremely rare sex chromosome aneuploidy characterized by the presence of three extra Y chromosomes in males, resulting in a total of 49 chromosomes. There are very few cases reported in medical literature. Symptoms described include intellectual disability, autism, social anxiety, selective mutism, and separation anxiety disorder. Physical symptoms include facial features, endocrine abnormalities and skeletal malformations.

Also known as 49,XXXXX; pentasomy X syndrome

49,XXXXX is an extremely rare sex chromosome aneuploidy characterized by the presence of three extra X chromosomes in females, resulting in a total of 49 chromosomes. Symptoms include intellectual disability, significant hypotonia, developmental delays, dental anomalies, and skeletal abnormalities (including clinodactyly, radioulnar synostosis, and valgus deformities of the feet). Growth deficiency is typical, with small hands and feet, and affected individuals often have congenital malformations such as cleft palate, cardiac defects, and genitourinary anomalies.

Other features may include hypergonadotropic hypogonadism, delayed or absent pubertal development, ocular findings, neurological complications (e.g., hydrocephalus, laryngomalacia), as well as immunological abnormalities, such as increased susceptibility to infections, which may occur in rare cases. The degree of hypotonia and developmental delay is generally more severe than in tetrasomy X, and prognosis varies depending on the extent of mosaicism and associated anomalies.