Keratosis linearis-ichthyosis congenita-keratoderma with mutations in pomp 10: Q82.8

Chaves AJ, 2006

Keratosis linearis with ichthyosis congenita and sclerosing keratoderm with mutations in POMP, known as KLICK syndrome for short, is a congenital or early childhood-acquired, generalized ichthyosiform dermatosis with palmoplantar keratoses, circular band structures around individual fingers and linear papules and plaques in the crook of the arm and wrists. The keratinization disorder is caused by an autosomal recessive mutation in the POMP gene on chromosome 13q.

Keratosis linearis with ichthyosis congenita and sclerosing keratoderm with mutations in POMP is caused by an autosomal recessive mutation in the POMP gene on chromosome 13q, which codes for the "proteasome maturation protein". This gene product is involved in the maturation of proteasomes. Genodermatosis is caused by a reduction in POMP levels leading to proteasome insufficiency in differentiating keratinocytes.

POMP is also known to be the causative gene for proteasome-associated autoinflammatory syndrome 2 (PRAAS2). It is assumed that the impaired proteasome assembly caused by the POMP mutation in "keratosis linearis with ichthyosis congenita and sclerosing keratoderm with mutations in POMP" leads to both an inflammatory reaction and a hyperkeratotic malformation. Inflammation caused by hyperactivation of innate immunity can lead to inflammatory diseases of the skin, also known as autoinflammatory keratinization diseases (AiKDs).

Epidermal hyperplasia with hypergranulose (no alkantholysis) and orthokeratotic hyperkeratosis.

Other variations in the POMP gene lead to systemic autoinflammatory diseases, such as proteasome-associated autoinflammatory syndrome 2 (PRAAS2). Affected individuals develop severe inflammatory, sometimes scarring neutrophilic dermatitis, autoimmunity and variable immunodeficiency. The symptoms already appear in the first weeks of life. Patients suffer from recurrent viral and bacterial infections (including Pneumocystis jiroveci), particularly of the respiratory tract, as well as episodic fever. Disseminated mycobacterial diseases have also been detected in isolated cases. Other features may include cyclical thrombocytopenia and seizures. CANDLE syndrome also belongs to this group.

1. Chaves AJ et al. (2006) Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK syndrome). Actas Dermosifiliogr 97:342-344.
2. Dahlqvist J et al. (2012) siRNA silencing of proteasome maturation protein (POMP) activates the unfolded protein response and constitutes a model for KLICK genodermatosis. PLoS One e294

3. Takeichi Tet al. (2020) KLICK Syndrome Linked to a POMP Mutation Has Features Suggestive of an Autoinflammatory Keratinization Disease. Front Immunol 11:641.