It is associated with intellectual disability of varying severity, characteristic "coarse" facial features, heart defects, and skeletal anomalies such as increased height, clinodactyly (incurved pinky fingers), and radioulnar synostosis (fusion of the long bones in the forearm).

Tetrasomy X has phenotypic overlap with a number of more common disorders, such as trisomy X and Down syndrome, and diagnosis is usually unclear prior to chromosomal testing.

Tetrasomy X has a variable presentation with a spectrum of severity, and lacks obvious defining clinical abnormalities that can lead to a diagnosis in the absence of testing.

[13] Clinodactyly, the bending inwards of the pinky finger, and radioulnar synostosis, the fusion of the long bones in the forearm, are frequent.

[18] Epilepsy in sex chromosome aneuploidies generally is mild, amenable to treatment, and often attenuates or disappears with time.

Expressive language delays and executive dysfunction are common heralds of behavioural issues, due to the difficulties they cause for educational, vocational, and social functioning.

[22] Parent reports describe children and young adults who are generally pleasant and affectionate yet shy, and have issues relating to temper tantrums, mood swings, and frustration at an inability to communicate.

[28] More recently, speculation has been based in genomic imprinting, with the suggestion that a similarly high number of paternal X-chromosomes would be incompatible with life.

[32] In Klinefelter syndrome, the most common and most studied sex chromosome aneuploidy, incidence increases substantially as maternal age rises.

[33] Less is understood about the role of maternal age in sex chromosome tetrasomy and pentasomy conditions, primarily due to their rarity, and no clear relationship has been established.

[37] Both are associated with hypotonia, mild facial anomalies such as hypertelorism and epicanthic folds, increased height, premature ovarian failure, and some reduction in intelligence.

While life expectancy is unclear, patients have been diagnosed in their 50s and 60s, and long-term follow-up of individual cases shows healthy aging with good physical health.

[46] Girls and women with tetrasomy X and good outcomes are typified by supportive family environments and strong personal advocacy for their success; "[t]he children have been exposed to many varied activities and experiences and are praised for their strengths, while their limitations and delays are minimised".

[2] Adolescents should undergo screening for ovarian insufficiency, as hormone replacement therapy may be required to mitigate the risk of osteoporosis.

[54] The late 1950s and early 1960s were a period of frequent ascertainment of previously unknown sex chromosome aneuploidies, with the discovery of the 48,XXXX karyotype being alongside that of 45,X0,[55] 47,XXY,[56] and 47,XXX[57] in 1959, 48,XXYY in 1960,[58] and 47,XYY the same year.

[59] One of the two women first diagnosed with tetrasomy X was followed up twenty-six years later in her late fifties, by which time she had left the institution and was living semi-independently with her sister; she was in good physical health, had experienced menarche and menopause at typical ages (14 and 50), and showed no signs of cognitive decline.

[5][60][61] The early preference for diagnosis of sex chromosome aneuploidy in selected samples, such as institution residents and prisoners, led to a biased perspective on the conditions that painted an unduly negative portrait of their phenotypes and prognoses.

Further research on sex chromosome aneuploidy via unselected samples such as newborn screening allowed for major conditions such as XYY syndrome, Klinefelter syndrome, and trisomy X to be re-defined by more representative phenotypes; however, rarer conditions such as tetrasomy X were not ascertained in any such studies, and therefore the medical literature continues to describe cases that were diagnosed due to developmental or behavioural issues.

[2] Aspects of the early studies remain accepted; a 1969 proposal that each supernumerary X chromosome reduces IQ by an average of 15 points[62] is still used as a rule of thumb.

Research into conditions such as tetrasomy X has been stymied by biased samples, outdated information, and a lack of publications above the case report level.

[65] The rarity of and variation in tetrasomy X limits the amount of specific support available, but major chromosome disorder organizations serve the condition and have members who are or are associates of people with it.