Also known as 49,XXXXX; Pentasomy X
What is 49,XXXXX syndrome?
49,XXXXX syndrome, also known as Pentasomy X syndrome, 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) have also been reported, 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.
Who gets 49,XXXXX?
49,XXXXX is rarer than sex chromosome trisomies, and the exact prevalence is unknown.
What causes 49,XXXXX?
49,XXXXX is caused by 3 extra X chromosome in females, most commonly due to the presence of extra X chromosomes in the egg or sperm at the time of conception, resulting from nondisjunction (when chromosomes do not divide properly), and is not typically inherited.
How is 49,XXXXX diagnosed?
49,XXXXX is a chromosome condition which can be diagnosed from blood tests. Tests that can diagnose 49,XXXXX include a karyotype (chromosome analysis looking at the number and structure of chromosomes in cells), a chromosomal microarray (a more detailed chromosome study looking for deletions or duplications across all chromosomes) or genetic sequencing (reading through the DNA sequence carried on the chromosomes). 49,XXXXX may be suspected based on physical or neurodevelopmental differences during childhood and can be identified before birth by prenatal screening and/or diagnostic testing, such as amniocentesis.
What is the treatment for 49,XXXXX?
Treatments for 49,XXXXX are specific to managing symptoms, including growth hormone treatment, physical therapy for hypotonia, monitoring for musculoskeletal abnormalities (imaging or surgery if indicated), genital evaluations and surgical treatment as indicated, evaluation for congenital defects such as cardiac defects or cleft palate with intervention as indicated, endocrine evaluation and hormone treatment for pubertal development, evaluation for immunological functioning, therapies for developmental delays, as well as neurodevelopmental, psychological and academic interventions.