Epidermolysis Bullosa Simplex with KLHL24 Mutations Is Associated with Dilated Cardiomyopathy

Abstract

et al. Inherited MST1 deficiency underlies susceptibility to EV-HPV infections. PLoS One 2012;7:e44010.

Phenotypic Features of Epidermolysis Bullosa Simplex due to KLHL24 Mutations in 3 Italian Cases

“…Indeed, the wide tissue distribution of KLHL24 suggests that mutations could affect other organs, in addition to skin (2). We recently found evidence of dilated cardiomyopathy (DCM) in 8 out of 20 EBS-KLHL24 patients (40%), the youngest being 25 years old (8). One additional EBS-KLHL24 family with lethal DCM has been reported (7).…”

Inherited epidermolysis bullosa: update on the clinical and genetic aspects

“…Several cases with typical signs of EB and mutations in KLHL24 have been described since then. 21 , 22 , 23 , 24 , 25 It is estimated that 5% of cases of EB S are associated with mutations in this gene. 1 The typical clinical signs of this subtype of EB S are still being characterized, as more studies and more patients are being described.…”

“… 23 , 24 Studies have demonstrated that 85% of patients with pathogenic variants in KLHL24 have some cardiac involvement, evidenced by a high level of biomarkers or dilated cardiomyopathy (40%). 25 , 26 Neurological problems, such as developmental delay, intellectual disability, memory problems, and myopathy were also described in some cases. 26 Future studies will be indispensable for a complete clinical characterization of this new subtype of EBS, designated in the most recent classification of EB as intermediateEB S with cardiomyopathy.…”

Clinical practice guidelines for laboratory diagnosis of epidermolysis bullosa

“…In syndromic EB types, expression of the affected genes in extracutaneous tissues leads to primary involvement of other organs or systems . Examples are muscular dystrophy in EBS with plectin deficiency; pyloric atresia in EBS with plectin deficiency and in JEB with integrin α6β4 deficiency; cardiomyopathy in EBS caused by KLHL24 or PLEC sequence variants and in skin fragility syndromes with DSP and JUP sequence variants; lung fibrosis and nephrotic syndrome in JEB with deficiency of the integrin α3 subunit; connective tissue abnormality in patients with PLOD3 gene mutation; or nephrotic syndrome in patients with CD151 deficiency . For detailed descriptions of the clinical features of EB, original and review articles are available …”