Dermatopathia Pigmentosa Reticularis

Updated: Nov 22, 2019
  • Author: Melba Estrella, MD; Chief Editor: Dirk M Elston, MD  more...
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Dermatopathia pigmentosa reticularis (DPR) is a very rare disorder with the diagnostic triad of generalized reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy. Many other dermatologic findings have been associated with this triad. These findings include adermatoglyphia, hypohidrosis or hyperhidrosis, palmoplantar hyperkeratosis, and acral dorsal nonscarring blisters. [1, 2] The reticulate pigmentation of DPR occurs at birth or during early childhood.

Dereure [3] noted that Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and DPR are two allelic ectodermal dysplasias related to mutations of the dominant gene coding for keratin 14 (KRT14). Other diseases caused by defects in keratin 14 include epidermolysis bullosa and Dowling-Mera disease. [4, 5, 6] Severe keratin 5 and 14 mutations induce down-regulation of junction proteins in keratinocytes, [7] which likely underlies all of these diseases. A number of missense mutations in KRT14 causing a DPR/NFJS phenotype have been reported. [8, 9] DPR resembles NFJS; they share reticulate pigmentation through adulthood, dental abnormalities, and alopecia. DPR and NFJS are considered to be allelic disorders, attributable to mutations on the nonhelical (E1/V1) head domain in the KRT14 gene, with consequent premature termination of protein synthesis. [10, 11]



Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are ectodermal dysplasias inherited in an autosomal dominant fashion. [12] The two disorders are both allelic and caused by dominant mutations in KRT14. Missense mutations can cause either of these diseases. [9] Both can manifest with the absence of dermatoglyphics, reticulate hyperpigmentation of the skin, hypohidrosis, and heat intolerance. Palmoplantar keratoderma, nail dystrophy, and enamel defects are common in NFJS, whereas diffuse alopecia is only seen in DPR.

In some NFJS pedigrees, the reticulate pigmentation fades after puberty and may disappear completely in old age. Hypohidrosis, the main problem for the patients, remains constant. Teeth are always severely affected, leading to early total loss. All patients with NFJS lack dermatoglyphics. Diffuse palmoplantar keratoderma may coexist with punctate keratoses that are sometimes accentuated in the creases or exhibit a linear pattern. Congenital malalignment of the great toenails can occur. [13]

Burger et al [14] examined 9 members of a five-generation Swiss family with overlapping signs of NFJS and DPR. Sanger sequencing of genomic DNA derived from patient lymphocytes revealed a unique 2-bp insertion in exon 1 of KRT14, leading to a frameshift and premature stop codon. They postulate that the identification of this intrafamilial overlap of phenotypes with the same KRT14 frameshift variant challenges the idea that DPR and NFJS are distinct disorders, representing instead a continuous phenotypical spectrum. [14]

p53 can act as a co-repressor to regulate KRT14 expression while epidermal cell differentiation occurs. [15] A half-site occurring on the p53-binding site on the KRT14 promoter involves activation by p63, suggesting that the differing p53-binding site's lengths could determine the gene regulation by different members of the p53 family of proteins. [16]

In 2002 Sprecher et al [17] assessed linkage for 17q in a large Swiss family with NFJS. Band 17q has been postulated to contain the gene for NFJS. They found a considerably narrow NFJS gene region, from 27 cM to 6 cM, flanked by D17S933 and D17S934, with a maximum multipoint logarithm of the odds score of 2.7 at marker locus D17S800. In addition, they studied a small family with DPR and reported that the linkage data they assembled suggested that DPR may map to band 17q. On 17q, the NFJS critical interval spans approximately 5.4 Mb and contains a minimum of 45 distinct genes. [18]

Goh et al [19] noted a patient of Malay ancestry with DPR secondary to a recurrent KRT14 p.R125C mutation. The patient had wiry scalp hair and digital fibromatous thickening in addition to reticulate hyperpigmentation over his trunk and proximal limbs. He also had onychodystrophy without noncicatricial alopecia.



Dermatopathia pigmentosa reticularis (DPR) is believed to be a genetic disorder of autosomal dominant inheritance. [12]

Apoptosis may play a key role in its pathogenesis, as evidenced by increased apoptotic activity in the basal cell layer expressing keratin 14. [11]




Since first described in 1958, dermatopathia pigmentosa reticularis (DPR) has been acknowledged as a very rare disorder, with approximately 21 reported cases among the regions of America, Europe, and Asia. [14]


Although most cases of DPR are reported in the European and US literature, no evidence indicates that DPR is associated with any particular race.


No sex predilection is documented for DPR.


The reticulate pigmentation associated with DPR occurs at birth or during early childhood.



The hyperpigmentation associated with dermatopathia pigmentosa reticularis (DPR) persists throughout life, showing no tendency of spontaneous fading.


Patient Education

Counsel the patient that the reticular hyperpigmentation persists throughout life, showing no tendency of spontaneous fading.

Consider genetic counseling to advise affected patients and their families of the medical implications of the disease and its pattern of inheritance. [20]

Advise patients with dermatopathia pigmentosa reticularis (DPR) to avoid sun exposure, which may trigger blister formation.