Cole disease results from mutations in the gene ENPP1. Functions of the ENPP1 protein include breaking down extracellular ATP into AMP and pyrophosphate, which is crucial to prevent calcification and mineralization, and assisting in cell signaling in response to insulin, which helps regulate and control transport of melanin from the melanocytes to keratinocytes.
In most cases, Cole disease is inherited in an autosomal dominant pattern, but de novo mutations also occur. The prevalence of Cole disease is unknown; only a few case studies have been reported in the literature.
For more information, see OMIM.
Q82.8 – Other specified congenital malformations of skin
711154007 – Cole disease
Differential Diagnosis & Pitfalls
- Flat warts
- Hypopigmented seborrheic keratoses
- Idiopathic guttate hypomelanosis
- Darier disease – leukodermic macules are a rare manifestation. Their development preceded the onset of the typical greasy keratotic papules. Leukodermic macules are recognized predominantly in darker skin types.
- Arsenic poisoning
- Confetti-type tuberous sclerosis
- Extragenital lichen sclerosus
- Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) manifests as both hypo- and hyperpigmented macules (reticulated hyperpigmentation). Punctate keratoderma usually appears later in life. Another unique feature of EBS-MP is early-onset blistering of the acral regions that often resolves or significantly improves with age.
- Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis – both conditions are caused by defects in the keratin 14 protein due to mutations in the KRT14 gene.
- Cantú syndrome (hyperkeratosis-hyperpigmentation syndrome) can also present with similar reticulated hyperpigmentation and punctate keratoderma.