The first report of krt5 mutation underlying acantholytic dowling-degos disease with mottled hypopigmentation in an Indian family

Abstract

Galli Galli disease (GGD) is the name given to a rare form of acantholytic Dowling-Degos disease. (DDD), the latter itself being a rare condition. We believe we are describing for the first time in Indian dermatologic literature a case of GGD in a family where 25 persons have DDD and have been able to document a KRT5 mutation in four members of the family. Whereas reticulate pigmentation is a hallmark of DDD there are rare reports of mottled pigmentation with multiple asymptomatic hypopigmented macules scattered diffusely along with the pigmentation. All the cases described here show a mottled pigmentation comprising hypo and hyperpigmented asymptomatic macules. After the clinical diagnosis was made by one of the authors (SV) in India, the German authors repeated histological examination and successfully demonstrated a heterozygous nonsense mutation, c.C10T (p.Gln4X), in exon 1 of the KRT5 gene, from various centers in Munich, Bonn, Dusseldorf and Friedrichschafen in Germany.

Atypical cases of Dowling-Degos disease

“…They pointed out that the hypopigmented lesions in the DDD spectrum has been underreported in India. [ 9 ] A similar mutation has been described in Chinese family with DDD with hypopigmented macules adjacent to the classic lesions showing histologic features of DDD. [ 10 ]…”

“…Verma et al . [ 9 ] described a case of GGD in an Indian family where 25 persons had DDD and they have been able to document a heterozygous nonsense mutation c.C10T in exon 1 of the KRT5 gene in four members of the family. All the cases described by them showed a mottled pigmentation comprising hypo- and hyperpigmented asymptomatic macules similar to our case.…”

Galli–Galli Disease: A Comprehensive Literature Review

“…An Indian family was found to carry a mutation c.10C > T, in which cysteine was replaced by threonine at position 10 [9]. In addition to the classic symptoms, this family exhibited hyperpigmentation on the extremities and face.…”

“…Mutations in the KRT5 gene were identified in 21 out of 69 patients diagnosed with classical Galli-Galli disease [8,9,18,[20][21][22][23][24]. The most common genetic alteration in the KRT5 gene is the c.418dupA missense mutation, which was found in 13 of the 21 patients with a KRT5 mutation [18,21,22,24].…”

“…During the inflammatory phase of the disease, itchy, erythematous, vesicular, and/or scaly papules may manifest in the same distribution, as well as on the trunk and proximal extremities [5][6][7]. Comedo-like lesions or pitted acneiform scars on the face may occasionally occur [6,8,9]. An emerging consensus posits a distinct GGD subset characterized by an atypical phenotype.…”