Genetic Skin Disorders with Heart Involvement: Recognition, Screening, and Counseling

Conclusions

• Genetic skin disorders can provide an early clue to underlying cardiac disease because the skin and heart share important developmental and structural pathways.
• Dermatologists are often the first clinicians to recognize these syndromes, so early suspicion can change outcomes for patients and families.
• Rasopathies such as Noonan, Costello, CFC, NF1, tuberous sclerosis, Carney complex, and H syndrome can have characteristic skin findings and specific cardiac associations.
• Disorders of keratinization and desmosomal proteins, including Naxos, Carvajal, and erythrokeratodermia variabilis, commonly lead to cardiomyopathy or arrhythmogenic heart disease.
• Some epidermolysis bullosa subtypes, especially KLHL24-related disease and recessive dystrophic/junctional EB, are associated with later dilated cardiomyopathy and require long-term follow-up even if the skin improves.
• In EB-associated cardiomyopathy, early recognition and treatment appear to improve stability, whereas missed disease can be fatal.
• Abnormal collagen/connective tissue disorders such as vascular EDS, Marfan syndrome, pseudoxanthoma elasticum, and PLOD3-related disease carry important vascular and valvular risks.
• Metabolic and premature aging disorders, especially Fabry disease and progeroid syndromes, can produce significant progressive cardiac disease.
• Initial cardiac screening with ECG and echocardiography should be considered broadly in these genodermatoses, with additional tests and surveillance tailored to the syndrome.
• Genetic testing, cardiology referral, and family counseling are essential because diagnosis often has implications for relatives and reproductive planning.