Random Dermatology MCQ - KID Syndrome

A 3-year-old child presents with generalized, thick, leathery, yellowish hyperkeratosis with a distinctive "honeycomb" pattern, profound bilateral sensorineural deafness, and vascularizing keratitis. The parents are consanguineous. Which of the following is the most likely diagnosis and its associated genetic mutation?

A) KID syndrome; GJB2 (Connexin 26)
B) Pachyonychia Congenita; KRT6A or KRT16
C) Vohwinkel syndrome; GJB2 (Connexin 26)
D) Netherton syndrome; SPINK5
E) Ichthyosis Hystrix; KRT1

Correct Answer: A) KID syndrome; GJB2 (Connexin 26)

Explanation

This presentation is classic for KID syndrome (Keratitis-Ichthyosis-Deafness), a rare congenital disorder.

Key Clinical Features of KID Syndrome:

• Keratosis (K): Generalized, spiky, stippled, or "honeycomb" patterned palmoplantar keratoderma and erythrokeratoderma. The skin has a characteristic thick, leathery, yellowish appearance.

• Ichthyosis (I): Not a true ichthyosis, but a progressive erythrokeratoderma.

• Deafness (D): Profound bilateral sensorineural hearing loss present from birth.

• Ocular: Vascularizing keratitis (corneal inflammation and neovascularization) leading to photophobia and impaired vision.

• Other Features: Increased susceptibility to bacterial and fungal (especially Candida) infections, scarring alopecia, and a predisposition to squamous cell carcinoma.

Genetic Defect and Pathophysiology:

• Gene: Mutations in the GJB2 gene, which encodes the gap junction protein Connexin 26.

• Inheritance: Most cases are autosomal dominant, but autosomal recessive inheritance exists. Consanguinity, as in this case, supports a recessive pattern.

• Mechanism: Connexin 26 is a component of gap junctions, which are channels that allow direct communication and exchange of ions and small molecules between adjacent cells. Mutations disrupt intercellular communication in the skin (leading to hyperkeratosis), the inner ear (causing deafness), and the cornea (causing keratitis).

Why Not the Other Options?

• (B) Pachyonychia Congenita: Features massive subungual hyperkeratosis (pachyonychia), focal palmoplantar keratoderma, and oral leukokeratosis, but not deafness or keratitis.

• (C) Vohwinkel syndrome: Also caused by GJB2 mutations, it features a "honeycomb" palmoplantar keratoderma and deafness. However, it is distinguished by the presence of pseudoainhum (constricting bands around digits) and the absence of the widespread erythrokeratoderma and vascularizing keratitis seen in KID syndrome.

• (D) Netherton syndrome: Features ichthyosis linearis circumflexa (migratory, double-edged scale), bamboo hair (trichorrhexis invaginata), and atopy, but not deafness or keratitis.

• (E) Ichthyosis Hystrix: Refers to severe, verrucous, generalized epidermal nevi or ichthyotic disorders like Epidermal Nevus syndrome, not a syndromic form with deafness and keratitis.

Management:

• Multidisciplinary care: Dermatology, audiology, ophthalmology.

• Hearing aids or cochlear implants for deafness.

• Lubricating eye drops and management of keratitis.

• Oral retinoids (e.g., acitretin) can improve the hyperkeratosis but must be used cautiously due to the increased risk of skeletal toxicity in children.

Prognosis:
Chronic and lifelong. The risk of squamous cell carcinoma necessitates regular skin surveillance.

Note: KID syndrome is a connexinopathy. The triad of Keratosis, Ichthyosis-like skin, and Deafness is pathognomonic. The distinctive "honeycomb" keratoderma and vascularizing keratitis are key diagnostic clues.