Dermatopathia Pigmentosa Reticularis

Updated: Aug 24, 2018
  • Author: Noah S Scheinfeld, JD, MD, FAAD; 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] The reticulate pigmentation of dermatopathia pigmentosa reticularis occurs at birth or during early childhood.

Dereure [2] noted that Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis are 2 allelic ectodermal dysplasias related to mutations of dominant gene coding for keratin 14. Other diseases caused by defects in keratin 14 include epidermolysis bullosa and Dowling-Mera disease. [3, 4, 5] Severe keratin 5 and 14 mutations induce down-regulation of junction proteins in keratinocytes, [6] which likely underlies all of these diseases. A number of missense mutations in KRT14 causing a dermatopathia pigmentosa reticularis/Naegeli-Franceschetti-Jadassohn phenotype have been reported. [7, 8]   Dermatopathia pigmentosa reticularis resembles NFJS; they share reticulate pigmentation through adulthood, dental abnormalities, and alopecia. Evidence confirms that dermatopathia pigmentosa reticularis and NFJS are allelic disorders. [9]



NFJS and dermatopathia pigmentosa reticularis may be variations on the same genetic defect. The 2 syndromes are both allelic, both caused by dominant mutations in KRT14. Missense mutations can cause either of these diseases. [8] The model of dominant mutations in KRT14 in NFJS has been questioned as some mice with involvement of this gene developed epidermolysis bullosa. [10, 11] p53 can acts as a co-repressor to regulate KRT14 expression while epidermal cell differentiation occurs. [12] 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. [13]

NFJS and dermatopathia pigmentosa reticularis are ectodermal dysplasias. They are inherited in an autosomal dominant fashion. [14] Both manifest with the absence of dermatoglyphics, reticulate hyper pigmentation 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 dermatopathia pigmentosa reticularis.

Still, the relationship of NFJS must be further clarified. 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. [15]

Sprecher et al [16] assessed linkage for chromosome 17q in a large Swiss family with NFJS. Band 17q has been postulated to contain the gene for NFJS. Sprecher et al [16] 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, Sprecher et al [16] studied a small family with dermatopathia pigmentosa reticularis and reported that the linkage data they assembled suggested that dermatopathia pigmentosa reticularis may map to band 17q. On 17q, the NFJS critical interval spans approximately 5.4 Mb and contains a minimum of 45 distinct genes. [17]

Goh et al noted a patient of Malay ancestry with dermatopathia pigmentosa reticularis 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. [18]



Dermatopathia pigmentosa reticularis is believed to be a genetic disorder with probable autosomal dominant inheritance. [14]




United States

Dermatopathia pigmentosa reticularis is rare. Approximately 4 cases of dermatopathia pigmentosa reticularis have been reported in the United States.


Since first described in 1958, approximately 12 cases of dermatopathia pigmentosa reticularis have been reported. Most of the cases were reported in Europe, with rare reports in America and Asia. Brar et al noted it in a 12-year-old Indian patient. [19]

Another report in 2013 from India noted a 21-year-old woman with dermatopathia pigmentosa reticularis who had generalized reticulate pigmentation, finger and toe nail onychodystrophy, and diffuse noncicatricial alopecia. In addition to these 3 manifestation of dermatopathia pigmentosa reticularis, she had poorly developed dermatoglyphics and palmoplantar keratoderma. [20]

In 2014 in the French literature, an additional case of dermatopathia pigmentosa reticularis was noted. [21]


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


No sex predilection is documented for dermatopathia pigmentosa reticularis.


The reticulate pigmentation associated with dermatopathia pigmentosa reticularis occurs at birth or during early childhood.



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