DSG1-pEDD (Desmoglein 1 – palmoplantar Epidermal Differentiation Disorder)

Commonly referred to as “Striate Palmoplantar Keratoderma”

Facts

• What does DSG1 stand for? – Desmoglein-1 is a gene commonly abbreviated as “DSG1.”
• What does the DSG1 gene do? – encodes a desmosomal protein, which helps maintain the structure of the epidermis¹
• What happens when DSG1 becomes mutated?- the barrier function of the skin is compromised²
• Clinical significance of mutation? – cellular hyperproliferation & hyperkeratotic

About DSG1-pEDD or Striate Palmoplantar Keratoderma

Skin disease caused by mutations in Desmoglein-1 is known as DSG1-pEDD or Striate Palmoplantar Keratoderma (SPPK).¹ However, not all cases of SPPK are caused by DSG-1 mutations and not all DSG-1 mutations lead to a phenotype specific to SPPK.³ SPPK is passed down from a parent to their offspring in an autosomal dominant inheritance pattern.² This means that it only takes one copy of the mutated DSG-1 gene from one parent to cause SPPK. The parent who has SPPK has a 50% chance of passing the mutated DSG-1 gene in each pregnancy. Genetic testing is necessary to determine whether or not an individual with symptoms of SPPK is caused by a mutation in the DSG-1 gene.¹

Symptoms of DSG1

Signs of DSG1 often appear at a young age.⁴ The disease is characterized by thick skin on the palms of the hands and soles of the feet.⁵ This skin is referred to as hyperkeratosis that is often in a striate or linear pattern. The striate hyperkeratosis typically extends down each finger as well as the palm of the hand. There are usually patches of hyperkeratosis found on the soles of the feet as well. ^2,5 Palmoplantar keratoderma that are caused by a DSG-1 mutation are only found in areas that undergo abrasion and high pressure. These keratoderma on the palms and soles are thought to be exaggerated by environmental stressors.⁴

IPCRR Data for DSG-1

Sixteen individuals fully enrolled in the International Pachyonychia Congenita Research Registry (IPCRR) were found to not be PC but have a mutation in Desmoglein-1 gene. Ten are in the United States, five are in the United Kingdom, and one is in Norway. Nine are female and seven are males. Below is select data from the registry.

Palmar Keratoderma	88%
Always (never goes away)	81%
Sometimes (clears up at times)	6%
Seldom (hands usually clear)	0%

Data from 2022 Sample Size N=16

References

1. Hammers CM, Stanley JR. Desmoglein-1, differentiation, and disease. J Clin Invest. 2013;123(4):1419-1422. doi:10.1172/JCI69071
2. Has C, Jakob T, He Y, Kiritsi D, Hausser I, Bruckner TL. Loss of desmoglein 1 associated with palmoplantar keratoderma, dermatitis and multiple allergies. British Journal of Dermatology. 2015;172(1):257-261. doi:10.1111/bjd.13247
3. Vodo D, O’Toole EA, Malchin N, et al. Striate palmoplantar keratoderma resulting from a missense mutation in DSG1. Br J Dermatol. 2018;179(3):755-757. doi:10.1111/bjd.16320
4. Martha B. Dua-Awereh, Yutaka Shimomura, Liv Kraemer, Muhammad Wajid, Angela M. Christiano, Mutations in the desmoglein 1 gene in five Pakistani families with striate palmoplantar keratoderma. Journal of Dermatological Science. 2009;  53(3):192-197
5. Barber AG, Wajid M, Columbo M, Lubetkin J, Christiano AM. Striate palmoplantar keratoderma resulting from a frameshift mutation in the desmoglein 1 gene. J Dermatol Sci. 2007;45(3):161-166. doi:10.1016/j.jdermsci.2006.11.013

Above photos are from individuals in the IPCRR with confirmed DSG-1 mutations.