KID Syndrome
KID syndrome is an acronym for the syndrome character- ized by keratitis, ichthyosis, and deafness, a term proposed by Skinner et al. in 1981.
GENETICS/BASIC DEFECTS
1. Genetic heterogeneity a. Sporadic in most cases
b. Existence of familial cases suggesting a genetic etiology i. A vertical transmission suggesting an autosomal
dominant disease
ii. The occurrence in two sisters born to consan- guineous, unaffected parents suggesting an auto- somal recessive inheritance
2. Caused by heterozygous missense mutations in the connexin- 26 gene, GJB2, which is implied in the normal corneal function, hair growth, and carcinogenesis. Mutations in several other genes [GJB3 (connexin-31), GJB6 (connexin- 30)], which encodes members of the connexin family of gap-junction proteins, are shown to be responsible for hear- ing impairment and skin disorders.
3. Pathogenesis: failure in development and differentiation of multiple stratifying epithelia
CLINICAL FEATURES
1. Cutaneous features
a. Abnormal skin at birth: red, dry, thickened, and leathery b. Subsequent development of keratodermatous, non-
scaly plaques
i. Generally develop during the first year of life ii. Described as verrucous, ichthyotic, doughy,
rugal, or elephant-skin-like
iii. Develop primarily on the face and extremities iv. Plaques sharply demarcated and map-like in
contour
v. Plaques symmetrically located on the face a) Especially the cheeks
b) With variable involvement of the forehead, ears, chin, and nose
c) Furrows in the thickened skin of the chin and around the mouth
vi. Transverse ripples marking the surface of plaques over the knees
vii. Follicular keratoses, occasionally with spine-like projections, on the extremities, eyebrows, scalp, earlobes, neck, and nose
c. Distinct keratoderma of the palms and soles
i. Pebbly excrescences and an intervening coarsely stippled pattern analogous to heavily grained leather
ii. Patulous stippling rendering a moth-eaten appearance
d. Abnormal hair
i. Sparse, fine, and sometimes absent scalp, eye- brow, and eyelash hair
ii. Pattern of patch scalp alopecia resembling pseudopelade
iii. Body hair may be absent iv. Nails
a) Thickened b) Hypoplastic c) Absent d) White
e) Infrequently normal 2. Ophthalmologic features
a. Invariably involving epibulbar structures with inflam- mation of the cornea
i. Vascularized keratitis in majority of cases ii. Secondary pannus formation
b. Photophobia
c. Varying degree of visual impairment d. Onset: usually before adolescence 3. Auditory features
a. Sensorineural deafness
b. Repeat otitis media and externa 4. Other ectodermal abnormalities
a. Dental abnormalities i. Carious ii. Brittle iii. Malformed
iv. Delayed adult dentition b. Hypohidrosis
5. Neuroectodermal abnormalities a. Short heel cord
b. Cerebellar hypoplasia 6. Other associated features
a. Normal intelligence b. Growth delay
c. Increased risk of developing squamous cell carcinoma d. Increased susceptibility to viral, bacterial and mycotic
infections
i. Most commonly reported pathogens a) Staphylococcus aureus
b)
Eschericia colic) Pseudomonas aeruginosa d) Trychophyton rubrum e) Candida albicans
ii. Invasive and overwhelming infection may be present in infancy and early childhood. Death secondary to overwhelming sepsis has been reported in infancy
iii. Infections typically persistent and recurrent, but usu- ally limited to the skin in older children and adults iv. No consistent pattern of immunologic dysfunc-
tion demonstrated in patients with KID syndrome
567568 KID SYNDROME
DIAGNOSTIC INVESTIGATIONS
1. Dental examinations for teeth abnormalities
2. Ophthalmological examination for corneal pathology and visual acuity
3. Audiologic examination to demonstrate sensorineural hearing loss
4. Histopathology of the skin a. Findings not specific b. Stratum corneum
i. Always hyperkeratotic, usually with a basket- weave pattern
ii. Orthokeratotic and occasionally parakeratotic c. Stratum granulosum: generally intact
d. Eccrine sweat glands appearing normal, although a diminished number and aberrant morphology have been noted
e. Absent or atrophic hair follicles indicating the cus- tomary state of alopecia
f. Follicular plugging is the rule
5. Molecular genetic study to detect connexin 26 gene (GJB2) mutation
GENETIC COUNSELING
1. Recurrence risk a. Patient’s sib
i. Autosomal dominant inheritance: not increased unless a parent is affected
ii. Autosomal recessive inheritance: 25%
b. Patient’s offspring
i. Autosomal dominant inheritance: 50%
ii. Autosomal recessive inheritance: not increased unless the spouse is a carrier or affected 2. Prenatal diagnosis: none reported to date 3. Management
a. No specific treatment for the skin lesions b. Isotretinoin with inconsistent results
i. May cause exacerbation of eye lesion a) Marked increase in pannus formation b) Marked increase in vascularization
ii. Side effects of higher doses of isotretinoin a) Corneal opacities
b) Punctate erosions c) Blepharo-conjunctivities
c. Ophthalmologic evaluations and follow up. Corneal grafts revascularize rapidly with subsequent loss of vision
d. Treat infections vigorously
e. Surveillance for skin and mucosal malignancy f. Hearing aids
g. Appropriate school placement
REFERENCES
Alvarez A, del Castillo I, Pera A, et al.: De novo mutation in the gene encod- ing connexin-26 (GJB2) in a sporadic case of keratitis-ichthyosis- deafness (KID) syndrome. Am J Med Genet 117A:89–91, 2003.
Caceres-Rios H, Tamayo-Sanchez L, Duran-Mckinster C, et al.: Keratitis, ichthyosis, and deafness (KID syndrome): review of the literature and proposal of a new terminology. Pediatr Dermatol 13:105–113, 1996.
Ghadially R, Chong LP: Ichthyoses and hyperkeratotic disorders. Dermatol Clin 10:597–607, 1992.
Gilliam A, Williams ML: Fatal septicemia in an infant with keratitis, ichthyosis, and deafness (KID) syndrome. Pediatr Dermatol 19:232–236, 2002.
Grob JJ, Breton A, Bonafe JL, et al.: Keratitis, ichthyosis, and deafness (KID) syndrome. Vertical transmission and death from multiple squamous cell carcinomas. Arch Dermatol 123:777–782, 1987.
Kelsell DP, Di WL, Houseman MJ: Connexin mutations in skin disease and hearing loss. Am J Hum Genet 68:559–568, 2001.
Langer K, Konrad K, Wolff K: Keratitis, ichthyosis and deafness (KID)- syndrome: report of three cases and a review of the literature. Br J Dermatol 122:689–697, 1990.
McGrae J: Keratitis, ichthyosis, and deafness (KID) syndrome. Int J Dermatol 29:89–93, 1990.
Richard G: Connexins: a connection with the skin. Exp Dermatol 9:77–96, 2000.
Richard G, Rouan F, Willoughby CE, et al.: Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis- ichthyosis-deafness syndrome. Am J Hum Genet 70:1341–1348, 2002.
van Geel M, van Steensel MA, Kuster W, et al.: HID and KID syndromes are associated with the same connexin 26 mutation. Br J Dermatol 146:938–942, 2002.
van Steensel MA, van Geel M, Nahuys M, et al.: A novel connexin 26 muta- tion in a patient diagnosed with keratitis-ichthyosis-deafness syndrome.
J Invest Dermatol 118:724–727, 2002.
Wilson GN, Squires RH Jr, Weinberg AG: Keratitis, hepatitis, ichthyosis, and deafness: report and review of KID syndrome. Am J Med Genet 40:255–259, 1991.
KID SYNDROME 569
Fig. 1. A 26-year-old woman with keratitis, ichthyosis, and deafness.
Cutaneous manifestations show sharply demarcated red-brown hyper- keratotic plaques on the central face, around both eyes, and upper and lower extremities.
Fig. 2. Marked hyperkeratosis is visible around the eye and the outer rim of the ear.
Fig. 3. Chronic Candida albicans onychia and paronychia with hyper- trophy of distal digits and hyperkeratosis of the skin are apparent on both hands.
