Background: Long-term infertility can be attributed to many factors, with the genetic factor being the most overlooked due to its many nonspecific morphological or endocrine signs. We present a rare case of a patient with progressive testicular failure associated with 48,XXYY syndrome.
Case presentation: A 39-year-old Arab man presented to our fertility clinic for fertility treatment. He was diagnosed with primary infertility, which had been present for 20 years at the time of presentation. Our patient had nonspecific morphological features of an abnormally wide neck with front slouching neck posture, clinodactyly of the third finger, and had moderate hypoandrogenemic features. A semen analysis revealed azoospermia. Genetic tests for azoospermia, including sex-determining region Y (SRY) detection and chromosome Y microdeletion, revealed no deletion present on the Y chromosome. Karyotyping was used and our patient was diagnosed with 48,XXYY syndrome.
Conclusion: Genetic testing (karyotyping and so on) played a key role in the diagnosis of our patient with long-term primary infertility secondary to 48,XXYY syndrome, and should play a vital role in all cases of long-term infertility, especially when presentation is accompanied by endocrine, skeletal, or morphological symptoms, signifying an underlying genetic factor.
48,XXYY syndrome was first described in the medical literature in 1960 by Muldal et al.  as an aneuploidy and a type of Klinefelter syndrome (47,XXY). Although phenotypically similar to Klinefelter syndrome, sharing features like hypergonadotropic hypogonadism , it is made distinct by symptoms of mental retardation and psychiatric disorders [3, 4]. The syndrome manifests later on in life with abdominal adiposity, small testicles, delayed development, behavioral disorders, learning disabilities, and delayed puberty, with such symptoms not presenting until early puberty [5–7]. Skeletal deformities were reported for 48,XXYY syndrome and could include radio-ulnar synostosis, osteoporosis, hyperostosis, pseudoepiphysis, kyphoscoliosis, and frontalis interna .
Our patient had a rare case of long-term primary infertility and progressive testicular failure secondary to 48, XXYY syndrome. Early diagnosis may have provided many treatment options before reaching the end stage of testicular failure. Genetic testing (karyotyping, and so on) plays a vital role in all cases of primary infertility presenting in the long term, especially when presentation is accompanied by endocrine, skeletal, morphological, or developmental symptoms, which could signify an underlying genetic factor.