Young adult with Cantú syndrome: dealing with a rare genetic skin disorder

Abstract

This case report of a young adult with Cantú syndrome (CS) illustrates a remarkable journey of learning how to cope with symptom management and emotional impact associated with a rare skin condition. We describe a 20-year-old woman with a CS-related mutation in ABCC9 resulting in clinical manifestations, including congenital hypertrichosis, facial dysmorphism and cardiomegaly. As of yet, no treatment is available for CS.

Little is known about the impact of CS and similar (skin) conditions on the life of affected individuals, and about their needs and preferences in this regard. Hence, we describe the psychosocial implications our case had to deal with immediately after her diagnosis. In addition, we outline her significant progress in managing disease-associated features and emotional stress prompted by considerable personal development and an increase in confidence. This example shows that a normal lifestyle is achievable for (newly diagnosed) individuals despite suffering from CS or a related skin disorder.

Background

Rare genetic diseases are heterogeneous conditions affecting only a small percentage of the population. Diagnosis of such rare conditions remains a challenge for affected individuals, doctors and healthcare systems due to insufficient characterisation of the natural history of many rare disorders. Next to undergoing a downright ‘diagnostic odyssey’, the majority of cases with rare diseases require complex clinical care due to multisystem dysfunctions. Hence, affected individuals and their families often apprehend significant impact on everyday life, work–life balance, mental health as well as social development and interpersonal relationships.

This is also the case for Cantú syndrome (CS; OMIM #239850), a rare autosomal dominant condition caused by gain-of-function mutations in ABCC9 and less commonly KCNJ8. CS consists of a wide constellation of clinical manifestations, including coarse facial features, congenital hypertrichosis and extensive cardiovascular anomalies, for example, cardiomegaly, patent ductus arteriosus, pericardial effusion, dilated and torturous cerebral blood vessels, and oedema.^1–3 The overall incidence of CS at birth is still unknown. Currently, we are not (yet) able to directly treat CS; clinical management merely involves symptomatic treatments to address secondary complications. However, recent studies hold great promise for pharmacological treatment of CS in the future.^{4 5}

CS creates a particular set of challenges for those affected. These include (1) the rarity of the disease, resulting in it being poorly understood by both peers and non-specialist healthcare professionals, (2) scarce information about long-term effects of associated features, (3) its potential to influence the psychosocial developmental, and (4) the combination of a stigmatising hair/skin disease that is also clinically complex and severe.

While it is essential to discuss and raise awareness regarding the negative implications of rare diseases on affected individuals and their families, reporting encouraging stories can be a powerful tool when tackling psychological stress associated with having rare conditions, especially for parents of a child diagnosed with a rare disease. Here, we present the journey of a young adult with CS and her impressive adjustment to a life with the disease. This shows that psychological well-being of such individuals can be ensured with the proper social support and counselling services in place.

Case presentation

The index case is a 20-year-old woman previously reported.^{2 3} She was born at 42 weeks following an uncomplicated pregnancy to healthy non-consanguineous Caucasian parents. Immediately after birth, the girl’s parents reportedly knew that ‘something was wrong’ because of extreme hair growth all over her body. However, the involved clinicians were not able to reach an accurate diagnosis at that time. Recurrent ear and chest infections resulted in breathing difficulties as a young child and required multiple penicillin treatments. She had speech therapy for her poor articulation due to a large tongue. Her motor, intellectual and puberty development were normal and she followed regular education. As an adolescent, she started to develop recurrent episodes of lower limb swelling extending to her ankles and feet (figure 1A). At present, she is attending college.

Figure 1.

Clinical features of Cantú syndrome. (A) Severe oedema of lower limb and around the ankle. (B) Hypertrichosis of the arms (not shaved). Image from social media post of index case after decision to stop shaving arm hair.

When growing up (until entering high school), she never worried about her social life or her overall place in society despite revealing extensive hair growth and other features mentioned above. At times, she did not realise to have a condition altogether.

Investigations

Due to the combination of congenital hypertrichosis and distinctive facial features, she was eventually suspected to have CS, which was confirmed by Sanger sequencing of ABCC9 (c.3460C>T, p.(Arg1154Trp)) at the age of 12 years. After being diagnosed, marking the end of her long diagnostic odyssey, she and her family felt greatly relieved as they were finally able to give her condition a name. Immediately after the diagnosis, she experienced difficulties when attempting to talk to peers about the disorder. Despite feeling somewhat extraordinary as being part of a small percentage of individuals with CS, she described a lack of empathy from others during conversations. Because of its rarity, CS is typically unknown by the general population. In secondary school, she experienced bullying, resulting in a negative self-image during adolescence.

After her diagnosis, she started attending our annual CS research clinics at the University Medical Center Utrecht, The Netherlands. Recent clinical examinations showed apart from her tall stature and macrocephaly, generalised hypertrichosis with thick scalp hair extending to her forehead and cheeks, and excessive body hair on her arms, legs and plantar part of her hands (figure 1B). Three-dimensional imaging of the face revealed epicanthal folds, full lips and a broad nasal bridge.³ To assess cognitive profile, social functioning and psychiatric symptoms, she was asked to complete the Social Responsiveness Scale-2 and the Achenbach System of Empirically Based Assessment. The results showed an overall scoring in the normal range (17 years of age). At the age of 18 years, she underwent a neurological examination, including motor and sensory skill evaluation, which revealed no abnormalities. Recent electrocardiography revealed eccentric hypertrophy of the heart with the left ventricular chamber being significantly dilated (139 g/m²). Additionally, ejection fraction was markedly increased (69%).

Differential diagnosis

Due to the overall rarity and the limited experience of physicians with CS, cases can initially be misdiagnosed with metabolic disorders, such as a mucopolysaccharidosis; or Beckwith‐Wiedemann syndrome, based on coarse facial features; or Pompe disease based on neonatal cardiomegaly.² Before receiving a molecular diagnosis of CS, our patient was misdiagnosed with Fabry disease, most likely based on distinctive facial features and limb swelling, as well as gigantism due to large birth weight and length.

Treatment

No drug treatment is available (yet) for patients with CS. Currently, clinical management of CS merely involves symptomatic treatments to address secondary complications. To monitor the reported cardiac abnormalities, she has annual echocardiograms. Peripheral oedema is being treated with compression stockings. In the past, she underwent cosmetic treatment of hypertrichosis. Laser removal of excess hair on the cheeks at the age of 13 years was not successful. At the age of 14 years, she felt the need to remove excessive body hair, including excess hair on the face, by waxing and/or daily shaving. When being asked to let hair grow naturally on her arms for 2 weeks in preparation for a dermatological evaluation as part of our study, she expressed noticeable reluctance at first, highlighting the associated social impact of the visual part of her condition.

Notably, not every patient might have access to symptomatic treatment for CS-related features. In particular, cosmetic treatment like laser hair removal is typically not covered by insurance and can be associated with high costs depending on the body part of interest and hair characteristics.

Outcome and follow-up

After her experience of being bullied for the physical appearance associated with CS, she started attending regular therapy sessions with a child psychologist focusing on the importance of body image and how the mental picture of the physical self influences interactions and responses, making it a major factor in her social and interpersonal relationships. For instance, she reportedly learnt to refrain herself from the immediate thought of being judged by her peers and to stand up for herself in case of confronting incidences. Prompted by therapy (10 sessions) and the associated growth in confidence as well as COVID-19-related social distancing measures, our case decided to stop removing excess hair on her arms at the age of 20 years. This significant step in her personal development received major support online after opening up about her journey on social media (figure 1B).

Our case has a stable support system in place consisting of her close family, grandmother and friends. She is an enthusiastic participant of social activities and exercises up to three times a week without experiencing any limitations.

Discussion

We present a young adult with CS, a rare genetic disorder resulting in excessive body hair growth, distinctive facial anomalies and a wide constellation of cardiovascular manifestations.

General knowledge of CS and its pathophysiology remains scarce and treatment options are limited. From a psychological perspective, this alone can have significant psychological implications for the patient resulting in decreased self-confidence and quality of life. Hypertrichosis, mentioned as the most impacting feature of the disease by a majority of patients, can cause severe emotional distress for patients, which may be increased for those who do not have access to permanent and successful laser hair removal due to high associated costs. This is not only the case for CS, but also other congenital skin conditions with no causative treatment options.

Studies on the quality of life of rare disease patients, however, mainly focus on disease-associated variables, presenting a pathophysiological model without the patient-centred perspective and exploring the psychosocial impact of a rare medical condition.⁶ The aim of this report was not only to illustrate the psychological impact of being affected with CS or a related disorder, but also to identify associated support needs which, when utilised correctly, can drastically improve the quality of life.

One important factor on psychological well-being of CS cases is perceived social support; the perception that there are others who care for the overall well-being and happiness of affected individuals. As illustrated by this case report, social support does not only include interpersonal exchange with immediate family and friends, but can also be received via social media. Nowadays, people diagnosed with a rare disease utilise social media to raise awareness about their condition by expressing their emotions and sharing their own experiences.⁷ They can share their story and exchange ideas and feelings so that they themselves create a real community on a specific topic. We show important benefits of social media participation for individuals with rare disorders, including increased confidence related to positive feedback received online.

Another important tool to increase the quality of life for patients of rare disease is counselling services. Hence, enhanced coordinated care among clinical geneticists and mental health practitioners might have significant implications not only for this small community of CS individuals, but also for other rare disease cohorts. For instance, in case of severe hypertrichosis, mental healthcare for patients in addition to medical care should be considered.

Finally, given the enormous range of studies involving rare diseases and single cases, knowledge about shared experiences for rare conditions is hampered. Case reports like this one, investigating the psychological and social experiences of people with rare disorders, can be one way of addressing the challenges of lack of knowledge in the society and the healthcare system, by summarising, discussing, and presenting an individual’s experience and their consequences in everyday life. Encouraging stories as presented here give hope to (newly diagnosed) patients and their family members, and ease worries and apprehensions they might have.

To get in contact with other CS patients and clinicians/researchers focused on the disorder, please visit http://cantu-syndromeorg.

Patient’s perspective.

When I was born, I was a large and heavy baby with a lot of hair growth. My parents immediately knew that something was not quite okay. The doctors first thought of a metabolic disease. Until I was 12 years old, I never knew that I was born with Cantú syndrome. I got along well with my classmates and had many friends. When they asked me about my hair, I always said that’s how I was born, this is who I am. In the beginning of high school, I was bullied a lot. Students who saw my excess hair called me a monkey and told me to shave. That hurt a lot, and I decided to shave my hair and pretend that there was nothing wrong with me.

Last year, I decided to let my arm hair grow again. Because I knew I couldn't do it alone, I contacted a psychologist, and talked a lot about it with friends. After multiple sessions, I regained a lot of confidence in myself and I learnt how to best tell my story to peers who do not know about the syndrome. From experience I have learnt that people close to you will accept you as you are. People are proud of me and they actually think it is cool to have a girlfriend with such a rare and special syndrome. You are beautiful just the way you are. Of course, there will be times when it gets difficult. But it always works out somehow and talking about it is the best tip I can give. I also have my insecurities about my swollen ankles, facial hair and big feet. But luckily, I can do something about that by wearing compression stockings and shaving. It’s not fun, but it’s part of it.

I look forward to doing more for other Cantú patients and helping where needed.

Learning points.

• Cantú syndrome (CS) cases are facing a unique set of challenges, including its rarity, unknown long-term consequences, and complex and stigmatising features.

• Continuous efforts will further elucidate the complex pathophysiology underlying CS, increasing the possibilities of ultimately identifying a pharmacological treatment for the condition.

• Rare genetic (skin) diseases, such as CS, affect individuals and their families on an emotional and sociocultural level, especially if no causative treatment is available. Social support and appropriate counselling can drastically improve the quality of life.

Ethics statements

Patient consent for publication

Obtained.