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Cole disease
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Cole disease

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Contributors: Zizi Yu, Susan Burgin MD
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Synopsis

Cole disease, also known as guttate hypopigmentation and punctate palmoplantar keratoderma with or without ectopic calcification, is a very rare disorder characterized by hypopigmented macules that typically affect the arms and legs and a punctate palmoplantar keratoderma. Both manifestations are present at birth or develop within the first year of life. Some patients with Cole disease develop calcifications within tendons, skin, or breast tissue.

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.

Codes

ICD10CM:
Q82.8 – Other specified congenital malformations of skin

SNOMEDCT:
711154007 – Cole disease

Look For

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

Differential diagnosis of guttate hypopigmented macules includes:
Also consider:
  • 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.

Best Tests

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Management Pearls

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Therapy

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References

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Last Reviewed: 05/31/2018
Last Updated: 07/23/2018
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Cole disease
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Cole disease : Irregular configuration, Hypopigmented macules, Arms, Legs
Copyright © 2019 VisualDx®. All rights reserved.