UCI DERMATOLOGYGRAND ROUNDSMARCH 30 , 2011

JENNIFER ARMSTRONG

Vohwinkel Syndrome vs. KID Syndrome

Connexin 26

Vohwinkel Syndrome and KID Syndrome are 2 clinically different syndromes both originating with missense mutation for Connexin 26 on Chrom 13.

What is a Connexin

A protein which is the building blocks that forms channels in gap junctions

Facilitates small molecules between cells

Important intercellular connections

Connexin & Hearing Loss Connection

Regulates K+ in Cochlea of inner ear.

Vohnwinkel Syndrome 2 Types

Both group of palmoplanter keratodermas

1 – Classical type with hearing loss Missense mutation of Connexin 26

2 – Ichthyosis- associated type Insertional mutation of the loricrin gene Develop thick ridged envelope

Vohwinkel Syndrome

……………………………………………………… Deafness, hearing impaired

…..…Palmoplanter Keratoderma, honeycomb appearance

………………………… Starfish shaped hyperkeratotic plaques

……………………………….………… autoamputation (pseudoainhum)

Treatment - Vohwinkel Syndrome

Rare Disease – Limited Options

Topical- Usually inadequate- Keratolytics (i.e salicylates, urea) - Retinoids

Systemic- Retinoids- Relapes after discontinue – almost all pts- Dose 60mg/Kg/PO

Surgical- Surgical release of constriction bands to

preserve digits

What is KID

KID syndrome is a rare disorder characterized by keratitis (with progressive corneal opacification), ichthyosis, and deafness (neurosensory).

Affects the epidermis but also Ectodermal tissue Predisposes patient to Squamous Cell Carcinoma on skin

and tongue Also susceptible to bacterial, viral, and fungal infections

KID

Acanthosis of the skin with a heavy-grained leather appearance.………..……………..

Hyperkeratotic Plaques………………….…

………………..…………Vascularizing Keratitis

…….……..…..Palmar Keratoderma

Nail Dystrophy, ………………………………..fungal infections

KID

Three months of age is typical age of cutaneous presentation Can start as general erythema Sometimes diffuse scaling Leathery skin

Ichthyosis

Not a classic ichthyosis but more a erythrokeratoderma

None scaling verrucous plaques, forehead and

cheeks

79% alopecia sparse to totalalis

Key Findings

Hearing loss Always by age 7 Variable degrees Subsequent speech delay

Occular manifestations 95% Progressive Corneal vascularization Worsened by retinoids

Similarities

Vohwinkels Syndrome KID Syndrome

Connexin 26 Missense Mutation

Connexin 26 Missense Mutation

Hearing Loss Hearing LossPalmoplanter Keratoderma Palmoplanter Hyperkeratosis

Differences

KID Syndrome……………………. Alopecia………………………………. Occular Keratitis

……………………………………………………...................….……. Small Teeth………………………………..…………. Hyperkeratotic fixed plaques

……………………………………………………….…………. Leathering of skin

…………………………………..…………. Increased squamous cell carcinoma

…………………………………………………...………..….…. Nail dystrophy

Differences

Vohwinkel Syndrome

Intact hearing in ichthyosis association type……………….……………….

Autoamputation (Pseudoainhum)…………….……………………….

Star shaped plaques on dorsum of hands………………………….

Differences

Vohwinkels Syndrome KID Syndrome

- Retinoids improve - Retinoids worsen

References

• Lucker GP, Van de Kerkhof PC, Steijlen PM. The hereditary palmoplantar keratoses: an updated review and classification. Br J Dermatol. Jul 1994;131(1):1-14.

• Camisa C, Rossana C. Variant of keratoderma hereditaria mutilans (Vohwinkel's syndrome). Treatment with orally administered isotretinoin. Arch Dermatol. Oct 1984;120(10):1323-8. 

• Solis RR, Diven DG, Trizna Z. Vohwinkel's syndrome in three generations. J Am Acad Dermatol. Feb 2001;44(2 Suppl):376-8.

• Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness ?see comments?. Nature 1997; 387(6628): 80-3.

• Richard G: Connexins: A connection with the skin. Exp Dermatol 9:77, 2000.

• Jan AY et al: Genetic heterogeneity of KID syndrome: Identification of a Cx30 gene (GJB6) mutation in a patient with KID syndrome and congenital atrichia. J Invest Dermatol 122:1108.

 • Philip Fleckman, John J. DiGiovanna. Dermatology Part 2. Disorders Presenting in Skin and Mucous

Membranes > Section 7. Disorders of Epidermal Differentiation and Keratinization >Chapter 47. The Ichthyoses.

• Images from: Geneva Foundation for Medical Education and Research including images published in Journal of Investigative Dermatolog, The American Journal of Human Genetics, Pediatric DermatologyVolume 15, Issue 3, Article first published online: 16 MAR 2009.