Testosterone replacement in 49,XXXXY syndrome: andrological, metabolic and neurological aspects

Abstract

SummaryWe report the case of a 19-year-old boy, presenting several congenital malformations (facial dysmorphisms, cardiac and musculoskeletal abnormalities), mental retardation, recurrent respiratory infections during growth and delayed puberty. Although previously hospitalised in other medical centres, only psychological support had been recommended for this patient. In our department, genetic, biochemical/hormonal and ultrasound examinations were undertaken. The karyotype was 49,XXXXY, a rare aneuploidy with an incidence of 1/85 000–100 000, characterised by the presence of three extra X chromosomes in phenotypically male subjects. The hormonal/biochemical profile showed hypergonadotropic hypogonadism, insulin resistance and vitamin D deficiency. The patient was then treated with testosterone replacement therapy. After 12 months of treatment, we observed the normalisation of testosterone levels. There was also an increase in pubic hair growth, testicular volume and penis size, weight loss, homeostatic model assessment index reduction and the normalisation of vitamin D values. Moreover, the patient showed greater interaction with the social environment and context.Learning points In cases of plurimalformative syndrome, cognitive impairment, recurrent infections during growth and, primarily, delayed puberty, it is necessary to ascertain as soon as possible whether the patient is suffering from hypogonadism or metabolic disorders due to genetic causes. In our case, the diagnosis of hypogonadism, and then of 49,XXXXY syndrome, was unfortunately made only at the age of 19 years.The testosterone replacement treatment, even though delayed, induced positive effects on: i) development of the reproductive system, ii) regulation of the metabolic profile and iii) interaction with the social environment and context.However, earlier and timely hormonal replacement treatment could probably have improved the quality of life of this subject and his family.

Sexual and developmental aspects of 49, XXXXY Syndrome: A case report

“…(Gropman et al., 2010; Sumathipala, Gamage, Wijesiriwardena, Jayasekara, & Dissanayake, 2012). Ultrasound findings including cystic hygroma, polyhydramnios, small penis and abnormal posturing might be suggestive of this condition (Mazzilli et al., 2016; Schluth et al., 2002).…”

“…Another study by Mazzilli et al. (2016) reported androgen treatment on a 19‐year‐old boy with a 49, XXXXY syndrome. The study reported normalisation of testosterone levels, an increase in testicular volume, an increase in penile size and an increase in pubic hair growth.…”

“…This pattern is typical for patients with de- Boys are usually described as being shy with low frustration tolerance, irritable but friendly and resistant to changes in their routines (Hou, 2004). The IQ of patients with 49, XXXXY syndrome typically falls below the 10th percentile, ranging from 20 to 60, while patients with 47, XXY syndrome often have an IQ ranging from 89 to 102 (Gropman et al, 2010;Mazzilli et al, 2016). It is well known that cognitive involvement in 49, XXXXY syndrome is more severe than other supernumerary X chromosome syndromes.…”

DNA methylation and behavioral dysfunction in males with 47,XXY and 49,XXXXY: a pilot study

“…Males with 49,XXXXY typically undergo testosterone treatment ( T ) to promote optimal sexual and neurocognitive development [ 37 ]. First, scores on the CBCL and BRIEF were compared between the 49,XXXXY no- T and 49,XXXXY T groups.…”

XXXXY Syndrome

“…There was also an increase in pubic hair growth, testicular volume and penis size, weight loss, homeostatic model assessment index reduction, and the normalization of vitamin D values. Moreover, the patient showed greater interaction with the social environment and context (Mazzilli et al 2016).…”