Diagnosing Rare Diseases and Mental Well-being: A Family’s Story

Orphanet Journal of Rare Diseases is proud to present this article by Zheqing Zhang. This blog post is based on the winning essay in beacon for rare diseases and Medics4RareDiseases' "Student Voice" contest, which is accepted for publication in our journal.

When we experience symptoms, most of us walk into the clinic or hospital expecting immediate answers. For individuals with a rare condition, the path to diagnosis can span months to decades, with an average diagnostic delay of four to five years. Here, I share the story of two sisters whose diagnostic journeys diverged then converged, reflecting on the impact of these experiences on mental well-being.

It took the death of two siblings for Sarah to be diagnosed. In March 2000, Sarah and Lizzie were three and seven years old, respectively, when their older brother died suddenly from an aortic dissection, aged fifteen. Lizzie was born with a heart murmur, but no other family members had cardiovascular issues, leading doctors to believe that her brother had a de novo mutation causing Marfan syndrome. The rest of the family tested negative for the condition, and the case was closed.

Eighteen years later, in August 2018, Sarah began experiencing unexplained neurological and pulmonary symptoms. In March 2019, she suffered a spontaneous pneumothorax. However, multiple examinations ruled out infection, cancer, and lupus. “My brother died from an aortic dissection and I think this is something related.” Sarah remembers saying, but doctors never referred her to a geneticist. Sarah suffered three further lung collapses and a surgery in between. Doctors suspected a connective tissue disorder, but no one considered vascular disorders or genetic testing.

In March 2020, 27-year-old Lizzie, nine-months pregnant, was admitted to hospital for emergency caesarean delivery. She developed unexpected placental abruption and liver laceration, followed by respiratory and cardiovascular complications three days later. Doctors failed to save her despite their best efforts. Autopsy revealed an aortic rupture, and genetic testing was consistent with vascular Ehlers-Danlos syndrome (VEDS). In the remaining family, Sarah was the only person to test positive, and it was assumed that this condition had also afflicted their brother.

Ehlers-Danlos syndromes (EDS) are rare inherited connective tissue disorders. VEDS, the most severe form, is characterised by fragile arteries, muscles, and internal organs, usually caused by a mutation in the COL3A1 gene. Despite VEDS having autosomal dominant inheritance, Sarah’s parents showed no signs of the disease. It is likely that Sarah’s mother had mosaicism, meaning that only some of her cells harbour a genetic mutation, which was passed on to three of her eight children.

The diagnosis brought clarity, and genetic testing revealed that Lizzie’s daughter had been spared. Sadly for Lizzie, her post-mortem diagnosis came too late. This was especially harrowing for her family, as the celebration of a new life was marred by a tragic death. As things happened so quickly, Sarah felt she never had time to fully process her emotions. Her hospital visits coincided with her senior year of college, adding stress onto an already difficult degree. Shortly after graduation, her life was turned upside down by her sister’s tragedy and her own diagnosis.

For Sarah, grappling with the grief of losing her sister and the lifelong implications of her diagnosis was a mental whirlwind – a strange mix of relief, guilt, anger, shock, and confusion. Arguably, the premature deaths of her siblings were worse outcomes, but they were spared the psychological trauma and survivor’s guilt, which affected Sarah profoundly. She was angry at herself for not pursuing it more, and angry at her doctors for not diagnosing it earlier. “I can’t believe we had to lose another person to finally get an answer,” she laments.

Mental health issues are common alongside rare diseases, and psychological support must not be neglected. Luckily, Sarah has assembled her own care team, which she calls her “Dream Team”, including a cardiologist, pulmonologist, neurologist, psychotherapist, and nutritionist, and also benefits from massage therapy and acupuncture. Through communities like the VEDS Movement, she has found friends with the same condition, adding to her support network. Like many, Sarah has become a patient advocate, and sharing her story is her way of educating the public and medical community.

Retrospectively, many clues were missed, and more efficient communication between healthcare providers, as well as taking a family history, could have helped. Discussing Lizzie’s case, a doctor proposed integrating rare diseases into the medical school curriculum. As many physicians are unfamiliar with rare diseases, patients often find themselves the expert. Healthcare providers should constantly identify and fill gaps in knowledge, never forgetting that medicine, especially timely diagnosis, requires lifelong learning.

Compared to her siblings, Sarah may have been “the lucky one”, but the story does not end here. For Lizzie’s husband and daughter, the loss of wife and mother will haunt them for decades. For Sarah, she has to navigate her new life with courage and faith. For all of us, a pressing question remains: How can we improve the physical and mental wellbeing of patients before (and after) diagnosis?

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