A Case Report of Turner Syndrome Diagnosed at Age 61 Years

Abstract

Here, we describe a case of Turner syndrome first diagnosed at 61 years of age. The patient’s chief complaint was general edema. A cardiologist was consulted, who performed echocardiogram and coronary heart computed tomography. Chromosomal analysis yielded inconclusive results for Turner syndrome. The patient’s karyotype was 45,X[17]/46,X,psu idic(Y)(q11.23), and she was referred to a gynecologist a time span. The patient was nulliparous with no history of sexual contact. We performed a prophylactic gonadectomy, but no malignancy was detected pathologically.

INTRODUCTION

Turner syndrome is a rare disorder caused by partial or complete X-chromosome defects affecting approximately 1 in 2,500 live-born females.

Around 50% exhibit monosomy X (45,X), while 5% to 10% possess an isochromosome duplication of the long arm of an X chromosome (46,X,i(Xq)). The majority of the remaining individuals display mosaicism for 45,X, with variant, which is accompanied by one or more alternate cell lineages.

It clinically presents with short stature, delayed puberty, ovarian dysgenesis, infertility, congenital heart disease, and hearing impairment [1,2].

When the syndrome presents as a mosaic karyotype, clinical presentations are often uncommon, which can be difficult to be recognized for primary care providers. Turner syndrome is typically diagnosed at an average age of 5.9 years, while the age at diagnosis of Turner syndrome mosaicism is 7.5 years [3].

In this report, we described a woman who was diagnosed with Turner syndrome mosaicism at 61 years of age.

CASE REPORT

A 61-year-old unmarried woman presented at our hospital with generalized edema. The patient’s height was 148.1 cm. Following echocardiography screening, she was diagnosed with a bicuspid aortic valve and moderate aortic stenosis. Coronary aortic computed tomography (CT) angiography revealed additional findings, including mild luminal narrowing of the aortic isthmus and persistent left superior vena cava.

In addition to the valvular disease, the patient also had a pectus deformity and scoliosis, which led physicians to consider a possible syndromic disease. For further workup, a cardiologist performed next-generation sequencing (NGS) to exclude the possibility of a syndrome, such as Malfan syndrome. FBN1, TGFBR2, and COL5A1 were identified as variants with uncertain significance. Additionally, the Y chromosome was detected in this woman.

Owing to the incidental finding of the Y chromosome, the patient underwent chromosomal analysis, and 45,X[17]/46,X,psu idic(Y)(q11.23) was confirmed. Hence, a 61-year-old patient was diagnosed with Mosaic-Turner syndrome and referred to a gynecologist for further evaluation of the possibility of gonadoblastoma.

At the first gynecological visit, the patient reported menarche at 27 years of age and menopause at 38 years of age. The patient was nulliparous with no history of sexual contact and never went any gynecologic evaluation before. We did CT and magnetic resonance imaging (MRI) for further workup.

Abdominal and pelvic CT did not identify any visible ovarian tissue. There was also no delineation of the bilateral ovaries on the MRI. Although the patient was 62 years old when she was referred to a gynecologist and there was no absolute gonadal tissue on imaging, we decided to perform prophylactic laparoscopic gonadectomy due to the possibility of gonadoblastoma [4].

In fact, when admission for laparoscopic gonadectomy, we performed a pelvic examination and were not able to insert a cotton swab more than 4 cm. Considering the pelvic examination findings and imaging results, which showed only a streaky uterus in the pelvic cavity, we verified the history with the patient. She changed her statement to say she had not experienced menstruation.

During the surgery, a streaky uterus and bilateral streaky gonads were observed (Fig. 1). Pathologically, the results were consistent with those of the bilateral streak gonadal tissues, and there was no evidence of malignancy.

Fig. 1. Operative findings of Turner syndrome patient. (A) A streaky uterus and bilateral streaky gonads were observed. (B) Left gonadal tissue is visible and the left ovary is not clearly visible. (C) Postoperative finding after bilateral gonadectomy.

As she did not receive hormone therapy, we did bone density test and results from her bone density test were consistent with those of osteoporosis (T-score: L2–L4 (AP) = –3.6, and left femoral neck = –2.8).

The patient is currently being treated for osteoporosis with denosumab and calcium carbonate, as she has never undergone hormone therapy. A cardiologist is monitoring the patient for heart disease.

This case report was approved by the Institutional Review Board of Samsung Medical Center (IRB No. 2023-08-154), and informed consent was obtained.

DISCUSSION

Turner syndrome is typically diagnosed during the neonatal or childhood period. The clinical presentation includes short stature, hearing impairment, or delayed puberty [5]. In this case, the diagnosis was made when the patient was over 60 years of age, which is substantially delayed even when considering the average age of mosaicism diagnosis. This case is also unusual because the diagnosis was initiated by echocardiography and cardiac CT performed as part of an evaluation for systemic edema rather than the typical clinical presentation associated with Turner syndrome.

Turner syndrome has various karyotypes. Monosomy X, also known as 45,X, accounts for approximately 50% of Turner syndrome cases and presents with the most severe phenotype due to the complete absence of one of the X chromosomes. Other than monosomy type, Turner syndrome can occur in mosaicism or variant type. As the present case, it can also be in mosaicism with various karyotype. In fact, in the chromosome analysis she had 48.8% of cells with monosomy X, 29.0% of cells with XY, and 22.2% of cells with psdueoidicentric chromosome Y, which can be differed from typical mosaicism, such as 45XO/46XX, 45XO/47XXX, 45XO/46XX/47XXX.

Depending on the specific karyotype, various clinical presentations can be observed. Turner syndrome has large phenotypic variability and patients with only few dysmorphism can be hard to distinguish from the general population. The intensity of clinical symptoms in TS generally aligns with the extent of the X-chromosome material deficiency.

Approximately half of Turner syndrome cases are diagnosed in teenagers with primary amenorrhea [6]. Our patient first reported menarche at 27-year-old and was later modified to never menstruate. Considering the surgical findings of an abnormal uterus, the patient would have never menstruated. Nevertheless, the patient did not present at any clinic, which was unusual, and this could have delayed the diagnosis. Physical examination revealed that the patient did not have a normal vagina. However, because she had never experienced coitus, she may not have recognized the abnormality, which would have additionally contributed to the delayed diagnosis.

In our patient, chromosomal analysis led to a diagnosis of Turner syndrome, as the patient’s NGS test revealed the presence of a Y chromosome. An isodicentric Y chromosome revealed by chromosomal analysis is one of the most common Y chromosomal abnormalities. The isodicentric Y chromosome is unstable due to the presence of two centromeres. Owing to its high instability, it often presents as mosaicism.

When an abnormal Y chromosome is present, gonadectomy is usually performed to prevent malignancy of the remaining gonads [7]. More commonly, this is performed in females with an XY karyotype, usually at a much earlier age, to eliminate the malignant potential of suggestive gonadal tissue. If her karyotype was just lacking some portion of X chromosome, she wouldn’t have needed this surgery. Fortunately, no malignancy was found in the streak gonads pathology, despite delayed surgery in our patient.

In this case report, we described a female patient diagnosed with mosaic Turner syndrome diagnosed at 61 years of age. Instead of the typical clinical presentation of Turner syndrome, the patient’s chief complaint was general edema, and the diagnosis was initiated by cardiac examination.

If a patient’s clinical features differ from the typical clinical course of the disease, physicians must consider another diagnosis. This is particularly important in cases with challenging diagnoses. Additionally, the patient’s medical history may not be accurate. Therefore, physicians should verify and correlate medical histories with other clinical findings. After confirming the diagnosis, long-term multidisciplinary care to improve the patient’s well-being is important.