Cole Disease: Guttate Hypopigmentation and Punctate Palmoplantar Keratoderma

Acromelanosis Albo-Punctata: A Distinct Inherited Dermatosis with Acral Spotty Dyspigmentation without Systemic Involvement

“…The case described by Siemens did not exhibit any blistering. This entity is different from reticulate acropigmentation of Kitamura [12], DSH [13,14] or Cole disease [15,16,17]. …”

“…Inheritance is supposed to be in an autosomal dominant way. Only a few reports have been published since the first description [15,16,64]. Histopathological examination of the hypopigmented macules reveals a normal melanin content of the melanocytes but a reduced melanin content of the keratinocytes, which could be explained by a defective transport of the melanosomes [16].…”

Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy

“…Some patients also show ectopic calcifications involving breast and spleen, tendons and skin . Histology and immunohistochemistry of hypopigmented areas show normal density and melanin content of melanocytes but decreased melanin and melanosomes within keratinocytes, suggesting an impaired melanosome transfer from melanocytes to keratinocytes …”

“…99,100 Histology and immunohistochemistry of hypopigmented areas show normal density and melanin content of melanocytes but decreased melanin and melanosomes within keratinocytes, suggesting an impaired melanosome transfer from melanocytes to keratinocytes. 101,102 In 2013, Eytan et al 99 demonstrated that Cole disease is caused by dominant mutations in the ectonucleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1) gene (Table S1) that is involved in the negative regulation of mineralization and insulin signalling. 103 Noteworthy, biallelic loss-of-function mutation in ENPP1 causes the severe generalized arterial calcification of infancy.…”

Association of Cole disease with novel heterozygous mutations in the somatomedin-B domains of theENPP1gene: necessary, but not always sufficient

“…1 Since then six further families with Cole disease (MIM 615522) have been reported and an autosomal dominant mode of inheritance has been proposed. [2][3][4][5] Recently, three heterozygous missense mutations were identified in ENPP1 encoding ectonucleotide pyrophosphatase/ phosphodiesterase1. 5 It is of note that bi-allelic mutations in this gene had been shown previously to underlie recessive conditions characterized by ectopic calcification such as generalized arterial calcification 6 or pseudoxanthoma elasticum 7 as well as autosomal recessive hypophosphatemic rickets with anterior spinal ligament ossification.…”