Erythrokeratodermia Cardiomyopathy Syndrome
What Is Erythrokeratodermia Cardiomyopathy Syndrome (EKC)?
Erythrokeratodermia cardiomyopathy (EKC) syndrome is a rare type of congenital skin and heart disease. The name comes from the two defining features of the disease: red, scaly skin (erythrokeratodermia) and heart issues (cardiomyopathy). The disease is caused by damaging genetic variants in the DSP gene which is important for maintaining the integrity of the skin and the heart to mechanical stress.
Longterm Course
Failure to thrive in infancy and childhood; sudden cardiac death or heart failure may occur; treatment with ustekinumab significantly improves skin and heart disease and failure to thrive.2–4
Key Findings
- Skin
ichthyosis, generalized erythrokeratodermia; some cases show pustular flares which may be associated with bacterial skin infections. - Hair
Wooly hair; alopecia has been reported in some cases; lighter hair than other family members in some cases - Nails
Oncodystrophy
Associated Findings
- Cardiac
Dilated cardiomyopathy (left ventricle dominant)2, heart failure, myocarditis - Other
Failure to thrive, secondary tooth agenesis, enamel issues, recurrent dental caries
What are the Signs & Symptoms?
Although EKC follows an autosomal dominant pattern of inheritance, most reported cases occur sporadically, meaning there is usually only one affected individual in a family.
At birth, individuals with EKC may show red, scaly skin and may show increased skin infections. Individuals with EKC commonly have a lack of eyebrows and eyelashes at birth.1 Occasionally, heart issues may be present at birth causing feeding difficulties, skin color changes, and increased irritability. However, in many cases, heart issues do not develop until infancy or childhood.
Individuals with EKC experience ichthyosis (scaling skin), redness and may experience flares where their skin disease gets worse due to bacterial infection, stress, or other triggers. They may also have issues with their fingernails and toenails, issues with their teeth such as gum infections, and hair issues. Some individuals have alopecia (lack of hair) while others have hair that is “woolier” or thicker than other family members and some with EKC have lighter hair color than other family members. Occasionally, individuals with EKC will experience issues with their eye such as cloudy spots in their cornea.2
Individuals with EKC may show signs of heart issues during infancy or childhood including poor feeding difficulties (in infants), rapid breathing, excessive sweating or fatigue while eating or playing. Occasionally, individuals with EKC may experience chest pain, shortness of breath, or rapid/abnormal heart rhythms acutely which may get diagnosed as myocarditis (or inflammation of the hart). It is very important to pay attention to signs and symptoms which may signal heart disease since sudden cardiac death or heart failure can occur in individuals with EKC.
Lastly, individuals with EKC show failure to thrive, meaning they fail to grow and gain weight at the same rate as other children.
At birth, individuals with EKC may show red, scaly skin and may show increased skin infections. Individuals with EKC commonly have a lack of eyebrows and eyelashes at birth.1 Occasionally, heart issues may be present at birth causing feeding difficulties, skin color changes, and increased irritability. However, in many cases, heart issues do not develop until infancy or childhood.
Individuals with EKC experience ichthyosis (scaling skin), redness and may experience flares where their skin disease gets worse due to bacterial infection, stress, or other triggers. They may also have issues with their fingernails and toenails, issues with their teeth such as gum infections, and hair issues. Some individuals have alopecia (lack of hair) while others have hair that is “woolier” or thicker than other family members and some with EKC have lighter hair color than other family members. Occasionally, individuals with EKC will experience issues with their eye such as cloudy spots in their cornea.2
Individuals with EKC may show signs of heart issues during infancy or childhood including poor feeding difficulties (in infants), rapid breathing, excessive sweating or fatigue while eating or playing. Occasionally, individuals with EKC may experience chest pain, shortness of breath, or rapid/abnormal heart rhythms acutely which may get diagnosed as myocarditis (or inflammation of the hart). It is very important to pay attention to signs and symptoms which may signal heart disease since sudden cardiac death or heart failure can occur in individuals with EKC.
Lastly, individuals with EKC show failure to thrive, meaning they fail to grow and gain weight at the same rate as other children.
How is it Diagnosed?
The skin symptoms of EKC may cause individuals to be diagnosed with ichthyosis or other related disorders which have red, scaly skin such as Netherton syndrome, psoriasis, or pityriasis rubra pilaris.
Heart workup includes electrocardiogram to measure the heart rhythm and echocardiogram to measure structural characteristics of the heart. Most individuals with EKC show normal heart rhythm but abnormal structure, specifically dilation of the left ventricle.2 Given the risk of sudden cardiac death or heart failure, anyone experiencing signs and symptoms of EKC or observing these symptoms in their child should undergo cardiac evaluation as promptly as possible.
Diagnosis of EKC is confirmed if genetic testing shows damaging variants in the desmoplakin (DSP) gene. You can participate in research studies and also receive genetic testing through the National Ichthyosis Registry at Yale University or for more information about genetic tests performed you can visit GeneDx, www.genedx.com.
Heart workup includes electrocardiogram to measure the heart rhythm and echocardiogram to measure structural characteristics of the heart. Most individuals with EKC show normal heart rhythm but abnormal structure, specifically dilation of the left ventricle.2 Given the risk of sudden cardiac death or heart failure, anyone experiencing signs and symptoms of EKC or observing these symptoms in their child should undergo cardiac evaluation as promptly as possible.
Diagnosis of EKC is confirmed if genetic testing shows damaging variants in the desmoplakin (DSP) gene. You can participate in research studies and also receive genetic testing through the National Ichthyosis Registry at Yale University or for more information about genetic tests performed you can visit GeneDx, www.genedx.com.
What is the Treatment?
Individuals with EKC respond well to certain anti-inflammatory medications repurposed from psoriasis, namely ustekinumab. These medications improve skin and hair symptoms, lead to height and weight gain, and can also improve heart issues. 2–4
Additionally, antisepsis (such as use of bleach baths) may help in some cases, and care should be taken to monitor for bacterial and fungal infections of the skin, which should be treated appropriately with antibiotics or antifungals.
Given the serious heart issues associated with EKC and the efficacy of anti-inflammatory therapies, individuals and families with EKC should seek treatment from both a dermatologist and cardiologist with experience treating genetic diseases.
Additionally, antisepsis (such as use of bleach baths) may help in some cases, and care should be taken to monitor for bacterial and fungal infections of the skin, which should be treated appropriately with antibiotics or antifungals.
Given the serious heart issues associated with EKC and the efficacy of anti-inflammatory therapies, individuals and families with EKC should seek treatment from both a dermatologist and cardiologist with experience treating genetic diseases.
References
- Boyden, L. M. et al. Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome. Human Molecular Genetics 25, 348–357 (2016).
- Sun, Q., Wine Lee, L., Hall, E. K., Choate, K. A. & Elder, R. W. Hair and skin predict cardiomyopathies: Carvajal and erythrokeratodermia cardiomyopathy syndromes. Pediatric Dermatology 38, 31–38 (2021).
- Paller, A. S. et al. The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: Immunophenotyping and response to ustekinumab. Journal of the American Academy of Dermatology 78, 498-505.e2 (2018).
- Hamzehlou, S. et al. Erythrokeratodermia-Cardiomyopathy Syndrome: Expanding the DSP Mutational Spectrum Beyond Proline Substitutions. Pediatr Dermatol https://doi.org/10.1111/pde.70048 (2025) doi:10.1111/pde.70048.
Clinical Resources
- Clinicians seeking to confirm a diagnosis should visit the Edvyce portal to submit a case to experts in ichthyosis.
- Learn more about FIRST’s Resources for individuals and families affected by Ichthyosis?
- Information about current clinical trials and research studies can be found here.
Types of Ichthyosis
- Congenital Ichthyosiform Erythroderma (CIE)
- Lamellar Ichthyosis
- Collodion Baby
- Darier Disease
- Epidermal Nevus
- Epidermolytic Ichthyosis
- Erythrokeratodermia Variabilis
- Erythrokeratodermia Cardiomyopathy Syndrome
- Harlequin Ichthyosis
- Ichthyosis Vulgaris
- Ichthyosis with Confetti
- Keratitis-Ichthyosis-Deafness (KID)
- Netherton Syndrome
- Pachyonychia Congenita
- Palmoplantar Keratodermas
- Sjögren-Larsson Syndrome
- X-Linked Ichthyosis
- Chanarin Dorfman Syndrome
- CHILD Syndrome
- Conradi-Hünermann
- Ichthyosis Hystrix with Deafness (HID) Syndrome
- Ichthyosis Hystrix Curth-Macklin
- Refsum Disease
- Trichothiodystrophy
Phenotype Names
Erythrokeratodermia cardiomyopathy syndrome, dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis
EDD Name
KRT16-pEDD
OMIM
Inheritance
Autosomal Dominant
Incidence
Exceptionally rare, less than 25 cases reported, incidence of ~ 0.1–0.5 per million births based on a de novo mutation rate for DSP SR6 EKC variants.1
Diagnostic Tests
Genetic testing of blood or saliva, electrocardiogram, echocardiogram
Age of First Appearance
Often at birth or during infancy; some may experience milder disease and some may not show symptomatic heart disease.3
Abnormal Gene
Desmoplakin (DSP)
Primary Symptom Photos
