International Journal of Health Sciences and Research www.ijhsr.org ISSN: 2249-9571

Case Report

Keratoderma Hereditariamutilans: A Rare Disorder of Keratinization

Shikha1, Mudita Gupta2, Pragya Gupta1

1Postgraduate Student, 2Assistant Professor, Department of Dermatology, Venereology and Leprosy, Indira Gandh Medical College, Shimla

Corresponding Author: Mudita Gupta

Received: 28/11/2016 Revised: 23/12/2016 Accepted: 26/12/2016

ABSTRACT

Keratoderma hereditariamutilans is a rare, autosomal dominant disorder of keratinization characterized by palmoplantar keratoderma and ainhum-like constrictions. We report herein a 16- year-old deaf –mute girl, since birth with palmoplantar hyperkeratosis with a honeycomb-like appearance, constricting band in her bilateral little finger, starfish keratosis on extensor surface of joints and nail changes.

Key words: Palmoplantar keratoderma, ainhum like.

INTRODUCTION marriage by full term normal vaginal Palmoplantar keratoderma (PPKs) delivery after an uneventful pregnancy. are a heterogeneous group of disorders Presented with persistent, palmoplantar characterized by hyperkeratosis of the palms keratoderma (Fig 1a,1b) since the age of 6 and soles. The majority of the disorders of months. Palmoplanter keratoderma this group are hereditary and a few are progressed steadily, and there was the acquired. Inherited PPKs can further be development of tight band around little classified into diffuse, focal PPK and finger of both hands since the age of around punctuate. Keratoderma hereditariamutilans 2 years. These bands and PPK subsequently (KHM) is also known as Vohwinkel lead to deformities of both the hands. syndrome. KHM is an autosomal dominant (Fig1a)There were starfish-like keratosis type of diffuse transgradient palmoplantar over the knuckles and hyperkeratotic keratoderma characterized by honeycomb papules over the dorsum of both feet. A appearance, pseudoainhum leading to auto constriction band around little finger. There amputation, stellate keratosis on knuckles, was no history of recurrent infections, teeth and associated with sensorineural deafness. loss, photosensitivity, photophobia, The most common mutation responsible is sweating abnormalities, muscle weakness or in the gene encoding connexin26, [1] which walking disability. No h/o any other is found in cochlea as well as in systemic complaints. She had 3 sisters and palmoplantar epidermis. one brother, none of them had similar complaints or any other disorder of CASE REPORT keratinization. A 16-year-old female deaf-mute Examination of the patient revealed since birth born of nonconsanguinous diffuse yellowish thickening of the palms

International Journal of Health Sciences & Research (www.ijhsr.org) 326 Vol.7; Issue: 1; January 2017 Shikha et al. Keratoderma Hereditariamutilans: A Rare Disorder of Keratinization

(Fig 1a), and soles (Fig 1b), honeycombed there were starfish-shaped keratosis on the (Fig. 2), by keratotic lesions encroaching on dorsa of the fingers and knees (Fig 6a) dorsum of hands and feet (Fig. 3), but there elbows (6b) and linear keratosis on the was no perilesional erythema. The keratosis flexor aspect of forearms. Hair, mucous was marked leading to clawing of both the membranes, and teeth were normal. hands. (Figure1a) A constricting fibrous Similarly, ocular, and musculoskeletal band was seen around bilateral little finger examination was normal. Patient on bedside (Fig4). Nails showed gross thickening with tests done for hearing was found to be deaf. horizontal ridges, and loss of cuticle (Fig5)

Figure1a honey combing and clawing of hands Figure 1b planter keratoderma

Figure 2: showing honey combing Figure 3: Transgradient PPK

International Journal of Health Sciences & Research (www.ijhsr.org) 327 Vol.7; Issue: 1; January 2017 Shikha et al. Keratoderma Hereditariamutilans: A Rare Disorder of Keratinization

Figure 4: pseudo ainhum in the little finger Figure 5: nail changes

Figure 6a: starfish keratosis over knee Figure 6b: starfish keratosis over elbow

Routine investigations were normal. translucent papular hyperkeratosis, Histopathological examination showed - gradually becoming confluent on hands and hyperkeratosis, spotty parakeratosis, regular feet, warty papules on the knuckles and acanthosis, and preserved granular layer. other extensor sites, coalesce into Audiometry revealed bilateral sensorineural pathognomic ‘starfish keratosis.’ The edge hearing loss. We started the patient on oral of the keratoderma at the wrists and isotretinoin (20 mg/day) which led to Achilles tendon consists of spiky digitate significant improvement after 1 month of hyperkeratotic projections onto normal skin, therapy with decreased keratoderma and sometimes showing koebnerization. arrest of the progression of fibrotic bands. Multiple keratosis on digits produce circumferential hyperkeratosis, which DISCUSSION predisposes to the formation of cicatricial In 1929, Vohwinkel first described bands and auto amputation. The little finger this syndrome in a 24-year-old woman who and fifth toe are most commonly affected as had a diffuse honeycombed palmar and was seen in our case. plantar keratosis, in addition to distal Two types of mutations of epidermal interphalangeal constrictions since 2 years differentiation have been identified in of age. The constrictions ultimately led to Vohwinkel syndrome. One is a novel auto-amputation. The patient also had mild- missense mutation of the gap junction to-moderate sensorineural deafness. protein beta 2 (GJB2 gene) coding Vohwinkel syndrome is a rare autosomal connexin-26, a gap junction protein. [3,4] dominant palmoplantar keratoderma, with This mutation is associated with the classic, approximately 50 cases reported in the sensorineural hearing loss-associated literature, which manifests in childhood and Vohwinkel syndrome. In Camisa syndrome becomes more evident in adulthood. [2] there is an insertional mutation of the Keratoderma hereditariamutilans also loricrin gene on the epidermal known as "Vohwinkel syndrome" and differentiation complex on 1q21. A "mutilating palmoplantar keratoderma" is a phenotype associated with ichthyosis. [5] rare autosomal dominant disorder although This protein is synthesized in the granular few sporadic cases have also been layer; it migrates to the cell periphery, described. No racial and sex predominance where it is deposited beneath the plasma is reported. The lesions start appearing in membrane. It links to several other proteins, infancy or early childhood and gradually forming cornified cell envelope. Thus, it progress with age. It begins as shiny or promotes an effective barrier between the

International Journal of Health Sciences & Research (www.ijhsr.org) 328 Vol.7; Issue: 1; January 2017 Shikha et al. Keratoderma Hereditariamutilans: A Rare Disorder of Keratinization body and the environment. [5] This mutation syndrome) in three unrelated families. Hum presents a palmoplantar keratoderma, Mol Genet 1999; 8: 1237-43. 2. O'Driscoll J, Muston GC, McGrath JA, Lam generalized thin desquamation on the HM, Ashworth J, Christiano AM. A extensor surfaces of the finger joints, and recurrent mutation in the loricrin gene constricting bands around the digits(pseudo- underlies the ichthyotic variant of ainhum).Other reported findings of classic Vohwinkel syndrome. Clin Exp Dermatol Vohwinkel syndrome are ,congenital 2002; 27:243-6. [6] 3. Kelsell DP, Wilgoss AL, Richard G, alopecia universalis, pseudopelade type Stevens HP, Munro CS, Leigh IM. alopecia, acanthosis nigricans, spastic Connexin mutations associated with [7] paraplegia, myopathy, nail changes, palmoplanter keratoderma and profound mental retardation, bullous lesions on the deafness in a single family. Eur J Hum soles, and seizures. [8] The differential Genet 2000; 8(2):141-2. 4. Solis RR, Driven DG, Trizna Z diagnosis of Vohwinkel’s syndrome .Vohvinkel’s syndrome in three generations includes other types of keratoderma that can J Am Acad Dermatol 2001;44(2 Suppl); be associated with auto-amputation of the 376-8 . digits: Olmsted syndrome, acral 5. Schmuth M, Fluhr JW, Crumrine DC, keratoderma, congenital pachyonychia, Uchida Y, Hachem JP, Behne M, et al. Structural and functional consequences of Sybert’s palmoplantar keratoderma, Meleda loricrin mutations in human loricrin disease and Gamborg-Nielsen palmar and keratoderma (Vohwinkel syndrome with [9] plantar keratoderma. As genetic and ichthyosis) J Invest Dermatol 2004; 122(4): molecular defects have not been elaborated 909-22. in all these conditions, they are 6. KrolAL.Keratodermas. In: Bolognia JL Jorrizo JL, Rapini RP. eds Dermatology. differentiated on clinical grounds mainly. Second ed USA: Mosby; 2008. P.777-89. The treatment is very difficult and tends to 7. James WD. Palmoplantar Keratoderma. In: be symptomatic: keratolytic agents and James WD, Berger TG, Elston DM. systemic retinoid [10] are used for the Andrews’s diseases of the skin clinical treatment of hyperkeratosis, but without dermatology.10thed.Philadelphia: Saunders; [2,11] 2006. p. 211-15. consistent results. Excision of the 8. Castro PJS, Fernandez CN, Subirana PQ, constricting bands, the use of grafts and Ortiz MP. Vohwinkel syndrome secondary flaps have been an alternative to to missense mutation D66H in GJB2 gene hyperkeratosis and auto amputation of the (connexin 26) can induce epileptic digits. The case is being presented because manifestations. Seizure 2010; 19(2):129-31. 9. Cavalcante, LIS; Holanda, EM; Almeida, the disease was sporadic and extensive TLP; Filho, JWA. Vohwinkel´s mutilating involvement was there. She had complete keratoderma: report of three familial cases sensorineural deafness with extensive An Bras Dermatol 2003; 78: 311-8. palmoplantar keratoderma leading to 10. Judge MR, McLean WHI, Munro CS. disability and deformity of hands. Disordrs of keratinization. In: Burns T, Breathnach S, and Cox N, Griffiths C. Rook's Textbook of Dermatology. 7th ed. REFERENCES Oxford;2004.34.79-34.104 1. Maestrini E, Korge BP, Ocana-Sierra J et al. 11. Bassetto F, Tiengo C, Sferrazza R, Belloni- A missense mutation in connexin 26, D66H, Fortina A, Alaibac M. Vohwinkel causes mutilating keratoderma with sensorineural deafness (Vohwinkel’s syndrome: treatment of pseudo-ainhum. Int J Dermatol2010; 49:79-82.

How to cite this article: Shikha, Gupta M, Gupta P. Keratoderma hereditariamutilans: a rare disorder of keratinization. Int J Health Sci Res. 2017; 7(1):326-329.

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International Journal of Health Sciences & Research (www.ijhsr.org) 329 Vol.7; Issue: 1; January 2017