Recurrent adnexal torsion in a teenager with hypermobile Ehlers-Danlos syndrome: A case report

Abstract

Hypermobile Ehlers-Danlos syndrome (hEDS) is the most common type of EDS, characterized by joint hypermobility, frequent dislocations, and chronic pain. Genetic markers are not typically used in diagnosis.

A 17-year-old clinically diagnosed with hEDS presented with recurrent lower abdominal pain, later attributed to intermittent partial adnexal torsion. Whole-genome sequencing revealed a missense mutation c.1691G > A (p.Arg564His) in the COL1A1 gene. She had undergone two exploratory laparotomies at ages 8 and 10 due to acute pain, resulting in a left adnexectomy and right detorsion with hydrosalpinx drainage. It was suspected that the recurrent adnexal torsion was linked to hEDS-related tissue elasticity, and so a laparoscopic right oophoropexy by shortening the utero-ovarian ligament was performed. At one-year follow-up, she was asymptomatic.

This case highlights the potential connection between hEDS and adnexal torsion, which may contribute to chronic abdominal pain, often misattributed to other conditions, such as irritable bowel syndrome.

Highlights

• •The management of a 17-year-old with hypermobile Ehlers-Danlos syndrome (hEDS) and recurrent adnexal torsion is presented.
• •Whole-genome sequencing revealed a COL1A1 mutation.
• •Laparoscopic oophoropexy successfully prevented further adnexal torsion.
• •Tissue elasticity in hEDS may contribute to recurrent adnexal torsion.
• •Clinicians should consider adnexal torsion in hEDS patients with abdominal pain.

1. Introduction

Adnexal torsion, a common gynecologic surgical emergency, refers to the twisting of both adnexal components, the ovary and fallopian tube. These can also rotate individually, resulting in ovarian or fallopian tube torsion, respectively. A complete or partial torsion results in complete or partial obstruction of the blood supply by compressing the ovarian vessels inside the infundibulopelvic ligament. Risk factors include the presence of an ovarian mass and a prior history of torsion, but its exact etiology remains unclear. Adnexa that may be more susceptible to torsion are those with greater mobility, possibly due to longer or more elastic utero-ovarian ligaments.

Ehlers-Danlos syndrome (EDS) refers to a group of inherited connective tissue disorders that are characterized by a combination of skin hyperextensibility, joint hypermobility, and tissue fragility. In 2017, a new international classification was introduced, which recognizes 13 EDS subtypes. The most common type is hypermobile Ehlers-Danlos syndrome (hEDS; formerly EDS type III), which exhibits the general features of EDS but with less severe manifestations. This remains a clinical diagnosis, based on the 2017 international criteria, as there are currently no definitive diagnostic laboratory tests [1].

Here, we present the case of a 17-year-old with recurrent adnexal torsion, presumptively due to hEDS.

2. Case Presentation

The management is described of a 17-year-old who had been an outpatient at a pediatric and adolescent gynecology (PAG) clinic since the age of 10 for recurrent abdominal pain attributed to partial adnexal torsion. At the initial visit to the clinic, she had presented with chronic, recurrent lower abdominal pain, for at least two years. Physical examination was unremarkable, but abdominal ultrasound revealed a 30 mm unilocular cyst with anechoic contents in the right adnexa, indicative of a hydrosalpinx. At 8 years old, she had been hospitalized in another pediatric hospital for acute abdominal pain and had had an exploratory laparotomy via a subumbilical midline incision, where left ovarian torsion was diagnosed. Subsequently, left adnexectomy and appendectomy were performed. Two years later, she was readmitted for acute abdominal pain and had a second exploratory laparotomy. A right hydrosalpinx with torsion, possibly due to an intraperitoneal adhesion between the fallopian tube and loops of bowel, was noted. Adhesiolysis, detorsion and drainage of the hydrosalpinx were performed.

Concurrently, she had been diagnostically evaluated by different specialists, including a pediatrician, a rheumatologist and an orthopedic surgeon, as she had been having musculoskeletal symptoms, mainly hyperflexible joints, multiple episodes of hip, shoulder and jaw subluxations and dislocations and chronic musculoskeletal pain. At 11 years old, she was diagnosed with hEDS. Whole-genome sequencing (WGS) revealed she was heterozygous for a missense mutation c.1691G > A (p.Arg564His) in gene COL1A1.

Following this diagnosis, she was referred for further evaluation. During cardiac evaluation, echocardiography revealed an atrial septal aneurysm (ASA) and a patent foramen ovale (PFO) with great mobility and oscillation into the left atrium. At 13 years old, percutaneous closure of the defect with self-expanding double-disc PFO occlude was performed.

In addition, she suffered from depression, migraines and episodes of vertigo, which were treated with paroxetine 20 mg daily and riboflavin 300 mg daily. She had experienced menarche at 10 years old. Her height was 160 cm, and her body weight was 46 kg, with a BMI of 18 (11 % of the average value for her age). Regarding her family history, her mother had migraines, joint hypermobility, scoliosis and was heterozygous for the same mutation, without meeting the diagnostic criteria for hEDS. The patient had two sisters; the older one had arthralgias, while the younger one had joint hypermobility and kyphoscoliosis. The patient and her family were racially Caucasian and ethnically Greek.

Following her initial visit, she was regularly assessed for the right adnexal mass and, after counseling, she was commenced on a low-dose combined oral contraceptive (COC) pill to suppress the formation of new ovarian cysts. Since then, there had been episodes of recurrent, lower abdominal pain, which had been treated conservatively. These episodes were attributed to intermittent partial adnexal torsion, suspected to be linked to the Ehlers-Danlos syndrome. Consequently, she was advised and agreed about surgical intervention.

Therefore, a laparoscopic approach was decided, during which a longer than usual ovarian ligament was noted, hypothetically secondary to hEDS (Fig. 1). A right oophoropexy by shortening the ligament (Fig. 2) was then performed, along with a salpingostomy in order to drain the hydrosalpinx.

Fig. 1.

Right adnexa during laparoscopy. The left grasper is on the right utero-ovarian ligament, which appears unusually long.

Fig. 2.

Right oophoropexy by shortening the utero-ovarian ligament.

Postoperatively, the patient complained about right hip arthralgia. This was further evaluated, as there was concern for a possible injury during laparoscopic surgery due to patient position and hEDS diagnosis. A plain radiograph was normal and a CT/MRI of the right hip was ordered a month later. This revealed femoroacetabular impingement syndrome (FAIS), a focal acetabular labral tear in the anterosuperior portion and iliopsoas muscle tendinitis, which were treated conservatively. At one-year follow-up she had no further abdominal pain.

3. Discussion

The patient was clinically diagnosed with hEDS using the 2017 international criteria, based on her history and physical examination. Genetic testing was ordered, as most other EDS subtypes have a causative genetic variant and needed to be excluded. However, hEDS is considered genetically heterogeneous and there is ongoing research on its pathophysiology and potential biological markers.

In the reported case, whole-genome sequencing (WGS) revealed heterogeneity for a missense mutation c.1691G > A (p.Arg564His) in the gene COL1A1. This gene is located on the long (q) arm of chromosome 17 (17q21.33) and encodes a component of type I collagen, called the pro-alpha1(I) chain. [2] Mutations in this gene are associated with a variety of connective tissue disorders (osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIA, Ehlers-Danlos syndrome Classical type, Caffey disease and idiopathic osteoporosis). [3]

This particular mutation results from a G to A substitution at nucleotide position 1691. Thus, the arginine at codon 564 is replaced by histidine, an amino acid with highly similar properties. It was previously reported as likely pathogenic in a patient with connective tissue abnormality. [4] It is currently considered of unknown clinical significance in the ClinVar database. [5]

The pattern of occurrence of hEDS is generally consistent with dominant inheritance with incomplete penetrance and variable expression among family members. [6] Indeed, this concurs with the case reported here, as the patient and her mother were found to be carriers of this mutation, but, unlike the patient, her mother did not meet the diagnostic criteria for hEDS. Nevertheless, she did have joint hypermobility and scoliosis, which suggests hypermobility spectrum disorder (HSD).

Patients with hEDS may have a variety of other associated symptoms and more than half experience abdominal pain. [7] This is often attributed to gastrointestinal causes, such as disorders of gut–brain interaction or irritable bowel syndrome. However, in the reported case, the patient's surgical history in combination with the ultrasound imaging of hydrosalpinx suggested recurrent partial torsion of the remaining adnexa and it was hypothesized that the hEDS-associated connective tissue laxity could contribute to this. Given the frequent episodes of abdominal pain and the need of hospitalization, laparoscopic surgical intervention was chosen after patient counseling.

This approach was also deemed essential for fertility preservation, which was a key consideration in this case. Even though the standard management should be a conservative laparoscopic approach, with detorsion and removal of any ovarian mass, the patient had previously undergone an adnexectomy during her first operation at another hospital. Oophorectomy was undertaken at the time. In light of this, preserving the remaining ovary was considered crucial.

Oophoropexy is the standard procedure for prevention of ovarian torsion, even though recent research suggests that it may be less effective than previously thought. [8,9] However, it remains the only available treatment, especially in young women with no pathology within the torted ovary. In addition, the longer than usual ovarian ligament that was recognized during laparoscopy was a risk factor for extended mobility of the remaining ovary. The patient's clinical improvement suggests that the procedure was preventing further ovarian torsion. She remained asymptomatic at follow-up and was considering stopping the COC for pain prevention.

A systematic search of the literature was conducted in order to find other reports, using “Ehlers Danlos” and “torsion” as search terms. Even though there was no other report of adnexal torsion in EDS, there were cases of appendiceal, testicular and even uterine torsion in patients with known or suspected EDS, where the authors also hypothesized that ligamentous laxity was a key feature. [[10], [11], [12]]

Patients with EDS undergoing surgery should receive special care during anesthesia and perioperative management. [13] Despite the best efforts of the care team, the patient experienced right hip pain postoperatively, which was attributed to a focal acetabular labral tear in the anterosuperior portion and iliopsoas muscle tendinitis. The most likely explanation was a perioperative injury, caused by either the patient positioning during laparoscopic surgery, the patient transfer to/from surgery, or postoperative mobilization. Thus, practitioners should be aware of such complications associated with EDS.

4. Conclusions

To our knowledge, this is the first case report in the literature of recurrent adnexal torsion in a patient with hEDS. Clinicians should be aware that patients with hEDS may be more susceptible to recurrent adnexal torsion due to associated tissue elasticity. This may be underdiagnosed, but it could explain some cases with chronic abdominal pain, which is usually attributed to other causes, such as irritable bowel syndrome.