arrhythmogenic cardiomyopathy with variable ectodermal abnormalities

Arrhythmogenic cardiomyopathy with variable ectodermal abnormalities is a multi-system disorder that primarily affects the heart and structures derived from the ectoderm. Cardiac issues, such as dilated cardiomyopathy and left ventricular dysfunction, coexist with distinctive ectodermal features including notched primary central incisors, abnormal hair patterns, and nail changes. The condition is linked to pathogenic variants in the PPP1R13L gene and is inherited in an autosomal recessive pattern. Precise prevalence estimates are not well established, and affected individuals may present at a young age with variable severity.

The clinical presentation is multi-system and variable. Cardiac manifestations include consistently present dilated cardiomyopathy along with left ventricular systolic dysfunction, myocardial fibrosis, mitral and tricuspid regurgitation, ventricular tachycardia, and findings such as right atrial enlargement, ventricular septal defect, bicuspid aortic valve, and patent foramen ovale. Ectodermal features are prominent and include a notched primary central incisor, high anterior hairline, sparse, coarse, dry, and woolly scalp hair, as well as nail dystrophy, corneal opacity, and even cleft lip in some cases. Additional features include failure to thrive, motor delay, myofiber disarray, polyhydramnios, and a low frequency of intellectual disability, reflecting the possible cognitive involvement. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the PPP1R13L gene, which plays a role in the normal development and function of cardiac muscle and ectodermal tissues. It is inherited in an autosomal recessive pattern, which means that an affected individual has received one altered gene copy from each parent. Families with a history of this condition may consider genetic counseling, as there is a 25% recurrence risk for siblings when both parents are carriers.

Currently, management focuses on supportive care and symptom management because there are no FDA-approved treatments specifically for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team that might include cardiologists, dermatologists, and developmental specialists. Regular surveillance is an essential part of long-term care, as ongoing monitoring can help detect complications early and guide timely interventions. Genetic counseling is recommended to help families understand their options and the inheritance pattern.

Outcomes for individuals with this condition vary widely, with some experiencing a period of stability following initial symptoms while others may develop complications over time. With current standards of care, including vigilant surveillance and multidisciplinary management, many individuals benefit from improved management of cardiac and developmental issues. Outcomes continue to evolve as standards of care improve, and severity and symptoms vary widely between individuals. Families are encouraged to connect with genetic counselors and specialized care teams for further guidance on long-term management.