A review of trisomy X (47,XXX)

Abstract

Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia and clinodactyly. Seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF) can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. Psychological features including attention deficits, mood disorders (anxiety and depression), and other psychological disorders are also more common than in the general population. Trisomy X most commonly occurs as a result of nondisjunction during meiosis, although postzygotic nondisjunction occurs in approximately 20% of cases. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined. Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Indications for postnatal diagnoses most commonly include developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF. Differential diagnosis prior to definitive karyotype results includes fragile X, tetrasomy X, pentasomy X, and Turner syndrome mosaicism. Genetic counseling is recommended. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. School-age children and adolescents benefit from a psychological evaluation with an emphasis on identifying and developing an intervention plan for problems in cognitive/academic skills, language, and/or social-emotional development. Adolescents and adult women presenting with late menarche, menstrual irregularities, or fertility problems should be evaluated for POF. Patients should be referred to support organizations to receive individual and family support. The prognosis is variable, depending on the severity of the manifestations and on the quality and timing of treatment.

Triple X Syndrome: Case Reports with Review of the Literature

“…1 Sendrom ilk kez 1959 yılında Jacobs ve ark. tarafından sekonder amonere nedeni ile başvuran 35 yaşındaki bir hastada, kromozom analizinde 47,XXX saptanması üzerine "süper dişilik sendromu" olarak tanımlanmıştır.…”

“…3 Uzun boy, mikrosefali, hipertelorizm, epikantal kıvrım, tremor, nöbet geçirme, hipotoni, klinodaktili, motor ve dil gelişiminde gecikme, tiroid fonksiyonlarında ve glukoz toleransında bozukluk, eşlik eden konjenital anomaliler ile tanı alan bir sendromdur. 1,4,5 Etiyolojisi hâlen tam olarak aydınlatılamamış olup, ileri anne yaşı bilinen en önemli risk faktörüdür. 4 Hastalarda fazladan olan X kromozomu anne kaynaklı olup, gamotogenez ya da postzigotik ayrışma sırasındaki (%58-63 oranında birinci mayoz, %16-17,4 oranında ikinci mayoz ve %18-19,6 oranında postzigotik bölünmedeki) hatalı ayrışmadan dolayı iki X kromozomu (46,XX) yerine üç X kromozomu (47,XXX) gelmektedir.…”

“…Sıklığı 1:1000 canlı kız doğum olarak bildirilmektedir. 1,4,7 Spesifik olmayan fenotipik özellikler ve doğumda hastaların tamamen normal olması nedeni ile klinikte gözden kaçan hastaların ancak %10 kadarına tanı konulabilmektedir. 8 Genellikle sporadik olarak ortaya çıkan bu sendromda hastaların çoğu uzun boy dışında normal fenotipe sahiptir.…”

The great escape

“…associated with X aneuploidy syndromes in humans such as Triple X (XXX, 1/1000 in females), Turner (XO, 1/2000-1/2500 in females) and Klinefelter (XXY, 1/500~600 in males) syndromes. [49][50][51] All of the supernumerary X chromosomes are inactivated, leaving only one X chromosome active. Thus, X-linked gene dosage is mostly compensated, but the gene dosage of escape genes is abnormal.…”

Patients with 47, XXX karyotype who experienced premature ovarian failure (POF): two case reports

“…Pubertal onset and sexual development are usually normal in trisomy X; however, there have been cases of ovarian or uterine dysgenesis described in children and young adults with trisomy X [4]. It should be noted that the most common cause of POF is sex chromosome aneuploidy, especially Turner's syndrome (45, X).…”