Epidermolysis Bullosa Simplex with KLHL24 MutationsQ82.8

Extensive (non-pyodermic) erosions are already present at birth, preferably on the extremities. These heal with tender scarring and mild hyperpigmentation. Traumatic blistering occurs in adolescence.

KLHL24 mutations can cause extracutaneous disease in humans in addition to the obvious cutaneous symptoms, with dilated cardiomyopathy being a strong association (Bolling MC et al. 2019). In addition, neurological diseases are also associated with mutations in KLHL24.

To what extent the cardiogenic component is associated only with specific variants popular currently still subject of research. A de novo pathogenic variant (c.2T>C (p.M1T) in KLHL24 (NM_017,644) appears to be associated with dermatologic symptomatology only (Xu X et al. 2021).

In epidermolysis bullosa simplex with mutation in KLHL24, whole-exome sequencing and targeted sequencing detected monoallelic mutations, c.1A>G and c.2T>C, in the translation initiation codon of the gene encoding Kelch-like protein 24 (KLHL24). These result in the encoding of a truncated polypeptide, abnormalities of intermediate filaments in keratinocytes and fibroblasts.KLHL24 mutations are associated with irregular and fragmented keratin 14. The c.1A>G mutation occurred de novo and was repeated in families from different countries (He Y et al. 2016).

Improvement of the dermatological symptomatology in the course of life

KLHL24 (KLHL24 is the acronym for Kelch Like Family Member 24) is a protein coding gene located on chromosome 3q27.1. KLHL24 is a member of the Kelch-like family of proteins that function as substrate-specific adaptors for cullin E3 ubiquitin ligases. The encoded protein is necessary for maintaining the balance between stability and degradation of intermediate filaments, a process essential for the integrity of the skin as well as the heart, among others. KLHL24 mutations are a cause of skin fragility but also of hereditary dilated cardiomyopathy.

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