A Case of Klinefelter Syndrome and Gender Dysphoria

Disorders of sex development are estimated to be prevalent in 0.1%–2% of the general population, based on studies in Europe and the United States (1). Klinefelter syndrome is one example of a sex development genetic disorder due to the presence of a 47,XXY genotype, which means that there is an extra X chromosome in each cell of the body. It is estimated to occur in 150 per 100,000 male newborns each year and is usually characterized by tallness, underdeveloped testes, and cognitive impairment (2). Gender dysphoria affects between 8.5%–20% of individuals with disorders of sex development (1).

The author presents a rare case of Klinefelter syndrome in a transgender male-to-female seeking sexual reassignment surgery. The complexity of this case stems from the unusual presentation of a genetic disorder, classically encountered in males.

Case

“Ms. N” is a 32-year-old single, transgender woman with no past psychiatric history, who was referred to the outpatient psychiatry clinic for further evaluation for sexual reassignment surgery to rule out psychiatric disorders and to assess for decision-making capacity. She wore full make-up, a colorful dress, and high-heeled shoes and appeared to be taller than the average woman. Strikingly, she told me, “I have a penis, and I want to remove it in order to be able to have babies.” She expressed mixed feelings of anxiety and frustration with her gender, and she wanted to get her sexual organs “repaired” in order to be able to conceive. She reported that since her early childhood she was different. She had never felt comfortable playing with other boys, and she did not show any interest in football or other culturally masculine-oriented physical sports. On the other hand, she preferred to play with dolls with her female siblings; she always assumed feminine roles in her imaginary plays. She also enjoyed watching her mother cook in the kitchen or gossiping with the neighbors over a cup of tea when her father was at work. As a teenager, she did not have the physical features expected for a male; she had scarce body hair, slightly enlarged breasts, increased abdominal fat, a soft voice, and small testis and penis, but she was unusually tall for her age. She had never had an erection like her brothers, and that made her more confident that she was not a man. Interestingly, these characteristics were due to her undiagnosed genetic disorder, but she interpreted these differences as evidence she was not, in fact, her biological gender.

She denied any suicidal or homicidal thoughts, depression or mania, delusions, or hallucinations at that time. She endorsed anxiety symptoms.

Ms. N reported that she was born male in a small town in Egypt and was the fourth child of seven siblings, with no complications at birth. She reported that her motor and language development were slower than her siblings, as well as her peers of similar age. She also stated that she was humiliated by boys at school, some of them had expressed interest in having anal sex with her, but she refused completely. Later, she decided to drop out of school before high school because “studying was very difficult” and she was getting poor grades. She stayed home for several years, helping with housework. However, she was in constant conflict with her family because she insisted that she wanted to be a woman, and she moved from her parents’ house in the countryside to work as a home-aide to a married lady in the city.

Ms. N disclosed to her employer that she was born male and that she wanted to undergo surgery for gender reassignment. Notably, the outpatient work-up for individuals seeking sex reassignment surgery revealed 47,XXY karyotype, and her blood tests showed low testosterone levels and raised gonadotrophins, which is consistent with Klinefelter syndrome. Moreover, her Wechsler Adult Intelligence Scale score of 75 disclosed “borderline intellectual functioning” according to DSM-IV criteria, although the IQ cutoff is no longer specified in DSM-5 (3).

Moreover, it was not clear whether sexual reassignment surgery would alleviate her stress or might increase suicide risk (reviewed in reference [4]).

Discussion

Ms. N is a transgender woman with a sex development disorder and with some degree of challenged intellectual functioning.

A challenge for this patient is that she grew up in a rural environment that could not accept her as being different, and she had to suffer constant humiliation and feelings of inferiority, especially at school from her male classmates. Although her mother and female siblings seemed to be accepting of her, her father felt ashamed of her appearance and behavior. Therefore, the cultural impact is enormous in this case. Firstly, her feelings of being rejected by society were reinforced. Secondly, her frustration with her gender drove her to want to prove that she was not male. Therefore, she insisted that obtaining female genitals and reproductive organs was critical to helping her to feel accepted by society as a “complete woman.”

Her genetic disorder has likely predisposed her to gender dysphoria (5), although it is a rare condition, since typically patients with Klinefelter syndrome identify or choose to identify themselves as males (2, 5). There is a dearth of literature on Klinefelter syndrome associated with gender dysphoria. Only few cases have been described in the literature (reviewed in reference [6]).

The main challenge for Ms. N’s treatment team was explaining to her the nature of her genetic disorder and that even if the sexual reassignment surgery was performed, she would not be able to conceive like other females.

The patient’s lack of understanding that could be explained by her borderline intellectual functioning represented a barrier for her to provide fully informed consent to undergo the operation, especially in appreciating the nature of her genetic disorder and its implications regarding her ability to conceive. Therefore, the team decided that she needed more time to be educated about the risks and benefits of the surgery and to appreciate the nature of the procedure and its consequences.

The patient was prescribed estrogen to promote the development of her secondary sexual characteristics, in addition to fluoxetine to help her with anxiety symptoms. Moreover, she received weekly individual psychotherapy sessions to help her have a safe transition to her full identity and to educate her about the nature of her genetic disorder and the implications of reassignment surgery. At first, she agreed to follow-up on a weekly basis and started taking her medications, but she was very frustrated that she would not achieve the same reproductive ability as other women. After a few weeks, she started to miss her appointments in the outpatient clinic and then discontinued her visits. All attempts to contact her were unsuccessful.

Conclusions

A major concern in patients with gender dysphoria is the risk of suicide (7). The above rare case raises awareness of the special needs of the transgender population and highlights the importance of having a well-prepared multi-disciplinary team to tailor a personalized plan depending on each individual’s unique situation.

Despite Ms. N not having any past history of suicidal ideation or behavior, this possibility had to be considered in the setting of increasing patient frustration and hopelessness. Therefore, targeted mental health intervention programs are necessary to address the exceptionally high suicide rates and increase treatment effectiveness (reviewed in reference [4]).

Key Points/Clinical Pearls