A case of 49,XXXYY followed-up from infancy to adulthood with review of literature.

49,XXXYY is an extremely rare sex chromosomal aneuploidy with only seven cases reported worldwide prior to this report.

• Only seven cases of 49,XXXYY had been reported worldwide at the time of publication.
• Among these cases, only three had been documented into adulthood.
• No cases of 49,XXXYY had previously been reported in Japan.
• This SCA has been identified in two scenarios: in vitro fertilization and abortion.
• 49,XXXYY is classified as a type of Klinefelter syndrome, similar to 47,XXY.

The patient presented with developmental delays and external genitalia abnormalities since early infancy but was not closely monitored until age 3, when chromosome testing confirmed the 49,XXXYY karyotype.

• The patient exhibited developmental delays and external genitalia abnormalities since early infancy.
• Close medical monitoring did not begin until the patient was 3 years old.
• Chromosome testing at age 3 revealed the karyotype to be 49,XXXYY.
• This represents the first reported Japanese case of this karyotype.

The patient with 49,XXXYY exhibited a broad phenotype including multiple physical, developmental, and endocrine abnormalities.

• Clinical features included delayed motor development and intellectual disability.
• Facial dysmorphisms and forearm deformities were documented.
• Additional findings included hip dysplasia, cryptorchidism, and micropenis.
• Endocrine abnormalities included primary hypogonadism.
• Essential tremor was also observed as part of the phenotype.
• Aneuploidy of the X chromosome was noted to lead to various progressive complications due to excess X chromosomes.

Long-term testosterone replacement therapy initiated since puberty resulted in no complications related to androgen deficiency and maintenance of normal metabolic and bone parameters.

• The patient underwent testosterone replacement therapy for primary hypogonadism since reaching puberty.
• He experienced no complications related to androgen deficiency throughout the follow-up period.
• He maintained normal lipid and glucose metabolism for a prolonged period.
• Bone density remained normal over the long-term follow-up.
• The authors noted there are no other reports on the long-term effects of testosterone treatment for this specific SCA.

The authors recommend appropriate testosterone replacement therapy for individuals with 49,XXXYY to prevent complications associated with androgen deficiency.

• Appropriate testosterone replacement therapy is recommended for individuals with 49,XXXYY.
• The recommendation is based on the long-term follow-up of this single case, which showed no androgen deficiency complications.
• The authors state this report will contribute to enhanced understanding of the 49,XXXYY phenotype.
• The findings are intended to aid in diagnosis, treatment, and genetic counseling of future cases.