Trisomy X Syndrome

The clinical course of trisomy X syndrome is variable, with many girls and women being asymptomatic from birth and throughout childhood [1] [2]. This may be one of the reasons why estimates suggest that only 10% of individuals having this mutation are clinically diagnosed [2]. However, numerous features are encountered in different age periods [1] [2] [3] [4]:

• Physical changes - Many neonates exhibit a lower birth weight than normal, accompanied by a normal or reduced head circumference [3]. On the other hand, increased height that is noted from birth, and accelerated growth throughout childhood and puberty, is one of the most common symptoms encountered in trisomy X syndrome [1] [2] [3]. Additional findings include the presence of epicanthal folds, hypertelorism, pes planus, pectus excavatum, clinodactyly and mandibular defects (prognathism and retrognathism) in rare cases [2] [3]. Hypotonia, as a result of mildly affected motor development, is also an important finding.
• Sexual and reproductive phenomena - Most patients have a normal pubertal development, but either precocious or delayed puberty, as well as recurrent miscarriages, ovarian or uterine dysgenesis and premature ovarian failure (POF), have been documented [1] [2].
• Cognitive and intellectual abnormalities - A variable degree of intellectual impairment, in addition to tall stature, is another key feature of trisomy X syndrome. Both verbal and performance IQ can be reduced in older children and teenage girls [3]. Difficulties in language skills are encountered as well [3]. In fact, children who experience learning difficulties, often require special education and early recognition of the disorder may significantly aid in reducing the IQ deficit [3].
• Psychological symptoms - Attention deficit accompanied by anxiety, mood changes, various adjustment disorders, and even psychotic disorders distinguished by paranoia are not uncommon, while social immaturity due to cognitive and intellectual impairment often leads to difficulties in forming relationships, irritability, and even aggression.

It is important to mention that structural organ abnormalities of the kidney (unilateral kidney and renal dysplasia) and the heart (atrial or ventricular septal defects, coarctation of the aorta and pulmonic stenosis) have been observed in a small, but a significant portion of patients [2] [3].

The diagnosis of trisomy X syndrome can be difficult to make if symptoms are mild or even absent, which is commonly the case. However, the physician must develop clinical suspicion toward this frequently undiagnosed syndrome in the setting of tall stature that is not supported by parental height, intellectual or psychosocial symptoms, and the presence of other typical features. For this reason, a detailed patient history, and physical examination are the most important parts of workup that will enable the physician to make a presumptive diagnosis. Increased maternal age (estimated around 33 years) is commonly observed in children who subsequently develop trisomy X syndrome, and further information regarding birth weight, as well as growth and development of girls throughout childhood by parents can be of essential importance [3]. Because several genitourinary and cardiac structural diseases have been diagnosed in trisomy X patients, ultrasonography of the abdomen and heart, respectively, should be performed. Moreover, magnetic resonance imaging (MRI) of the brain and electroencephalography (EEG) are recommended during workup, but apart from a reduced brain volume, they yield normal findings in virtually all patients [2] [3]. Genetic studies are necessary to make the diagnosis [1]. Analysis of the karyotype in cells will show an additional X chromosome, and the same finding can be identified prenatally when chorionic villus sampling (CVS) or amniocentesis can detect changes in the number of chromosomes [1] [2].

1. Afshan A. Triple X syndrome. J Pak Med Assoc. 2012;62(4):392-394.
2. Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L. A review of trisomy X (47,XXX). Orphanet J Rare Dis. 2010;5:8.
3. Otter M, Schrander-Stumpel CT, Curfs LM. Triple X syndrome: a review of the literature. Eur J Hum Genet. 2010;18(3):265-271.
4. Otter M, Schrander-Stumpel CT, Didden R, Curfs LMG. The psychiatric phenotype in triple X syndrome: New hypotheses illustrated in two cases. Dev Neurorehabil. 2012;15(3):233-238.

• Mosaic Trisomy 1
  User50434, 2019-03-02 18:52