J Korean Ophthalmol Soc.  2008 Sep;49(9):1532-1538.

Ocular Manifestations and Histologic Characteristics of Keratitis-Ichthyosis-Deafness (KID) Syndrome

• Jeong JH
• Chun YS
• Lee SH
• Jeong HS
• Kim JC

Abstract

PURPOSE
Keratitis-ichthyosis-deafness (KID) syndrome is a congenital ectodermal disorder presenting the triad of vascularizing keratitis, erythrokeratoderma, and sensorineural deafness. Ocular manifestations such as hyperkeratinization of the eyelids, loss of eyelashes, keratoconjunctivitis sicca, corneal erosions, ulceration, neovascularization, and scarring opacity may be absent or mild, but if present and severe, they can lead to major visual loss. We report a patient with KID syndrome with severe ocular manifestations and the histologic characteristics of a corneal lesion.
CASE SUMMARY
A 5-year-old boy was referred to the Ophthalmology Department for bilateral hyperkeratinization of eyelids, bare eyelashes, and corneal opacity. He showed hyperkeratotic skin lesions and sensorineural hearing loss. Molecular analysis showed a mutation in the GJB2 gene and confirmed the diagnosis of KID syndrome. Initial conservative treatment did not preserve ocular surface integrity, and instead it was maintained by surgical procedures including superficial lamellar keratectomy with amniotic membrane transplantation. The histologic characteristics of corneal lesions are abnormal epithelial differentiation, absence of connexin 26 expression, and partial destruction of the basement membrane.

Keyword

Histologic characteristics; KID syndrome; Ocular manifestations

MeSH Terms

Amnion
Basement Membrane
Cicatrix
Connexins
Corneal Opacity
Deafness
Ectoderm
Eyelashes
Eyelids
Hearing Loss, Sensorineural
Humans
Ichthyosis
Keratitis
Keratoconjunctivitis Sicca
Ophthalmology
Preschool Child
Skin
Transplants
Ulcer
Connexins
Deafness
Ichthyosis
Keratitis

Figure

• 

  Figure 1. Clinical appearance of a 5-year-old boy with KID syndrome. (A) Frontal view of face showed scarring alopecia and hyperkeratotic skin lesions. (B) Palmoplantar hyperkeratosis.

• 

  Figure 2. Slit lamp photographs of the right eye of a pateint with KID syndrome before surgery. (A) Hyperkeratic lid lesions and sparse lashes. (B) Gray-white elevated scarring opacity was observed on the central cornea. (C) Epithelial erosions were observed with fluorescein stain.

• 

  Figure 3. Slit lamp photographs of right eye after surgery. Lamellar keratectomy and amniotic membrane transplantation were done. (A) Central scarring opacity was regressed at post operative 4months. (B) A complete epithelization was achieved.

• 

  Figure 4. Histopathology of the corneal lesion. High-power magnification showed the characteristic squamous cell hyperplasia and partial destruction of Bowman’s layer (arrow). (hematoxylin-eosin stain, ×400).

• 

  Figure 5. Immunohistochemical staining for cytokeratin of the corneal lesion of KID syndrome. It shows strong immunopositivity to cytokeratin 3 in the suprabasal layer (A), to cytokeratin 5 in all epithelial layer (B). Hyperkeratosis of the cornea shows special features of the keratin pearl formations (arrows). It shows immunopositivity to cytokeratin 10 in superficial layer (C), to cytokeratin 13 in suprabasal & superficial layer (D) (Original magnification ×400 in all of the photomicrographs).

• 

  Figure 6. Immunohistochemical staining for connexin of the corneal lesion of KID syndrome. It shows positive immune staining to connexin 43 in the suprabasal and middle layer (A, Original magnification ×400), but negative immune staining to connexin 26(B, Original magnification ×400).

• 

  Figure 7. Immunohistochemical staining for basement membrane of the corneal lesion of KID syndrome. There are partial absences of the staining in the basement membrane (arrows) to collagen Ⅳ (A, Original magnification ×400) and to laminin 5 (B, Original magnification ×400).

Reference

References

1. Skinner BA, Greist MC, Norins AL. The keratitis, ichthyosis, and deafness (KID) syndrome. Arch Dermatol. 1981; 117:285–9.

2. Alvarez A, del Castillo I, Pera A. . De novo mutation in the gene encoding connexin-26 (GJB2) in a sporadic case of keratitis-ichthyosis-deafness (KID) syndrome. Am J Med Genet. 2003; 117:89–91.

3. Richard G, Rouan F, Willoughby CE. . Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. Am J Hum Genet. 2002; 70:1341–8.

4. Yotsumoto S, Hashiguchi T, Chen X. . Novel mutations in GJB2 encoding connexin-26 in Japanese patients with keratitis-ichthyosis-deafness syndrome. Br J Dermatol. 2003; 148:649–53.

5. van Steensel MA, van Geel M, Nahuys M. . A novel connexin 26 mutation in a patient diagnosed with keratitis- ichthyosis-deafness syndrome. J Invest Dermatol. 2002; 118:724–7.

6. Simon AM, Goodenough DA. Diverse functions of vertebrate gap junctions. Trends Cell Biol. 1998; 8:477–83.

7. Langer K, Konard K, Wolff K. Keratitis, ichthyosis and deafness (KID)-syndrome:report of three cases and a review of the literature. Br J Dermatol. 1990; 122:689–97.

8. Caceres-Rios H, Tamayo-Sanchez L, Duran-Mckinster C. . Keratitis, ichthyosis, and deafness (KID syndrome): review of the literature and proposal of a new terminology. Pediatr Dermatol. 1996; 13:105–13.

9. Gilliam A, Williams ML. Fatal septicemia in an infant with keratitis, ichthyosis, and deafness (KID) syndrome. Pediatr Dermatol. 2002; 19:232–6.

10. Wilson GN, Squires RH Jr, Weinberg AG. Keratitis, hepatitis, ichthyosis, and deafness:report and review of KID syndrome. Am J Med Genet. 1991; 40:255–9.

11. Gicquel JJ, Lami MC, Catier A. . Limbal stem cell deficiency associated with KID syndrome, about a case [in French]. J Fr Ophtalmol. 2002; 25:1061–4.

12. Sonoda S, Uchino E, Sonoda KH. . Two patients with severe corneal disease in KID syndrome. Am J Ophthalmol. 2004; 137:181–3.

13. Messmer EM, Kenyon KR, Rtittinger O. . Ocular manifestations of keratitis-ichthyosis-deafness (KID) syndrome. Ophthalmology. 2005; 112:1–6.

14. Kim L, Lee DH. A Case of Keratitis, Ichthyosis and Deafness (KID) Syndrome. J Korean Pediatr Soc. 2003; 46:1135–8.

15. Grob JJ, Breton A, Bonafe JL. . Keratitis, ichthyosis, and deafness (KID) syndrome. Vertical transmission and death from multiple squamous cell carcinomas. Arch Dermatol. 1987; 123:777–82.

16. Nazzaro V, Blanchet-Bardon C, Lorette G, Civatte J. Familial occurrence of KID (keratitis, ichthyosis, deafness) syndrome. Case reports of a mother and daughter. J Am Acad Dermatol. 1990; 23:385–8.

17. Kikuchi T, Kimura RS, Paul DL. . Gap junction systems in the mammalian cochlea. Brain Res Brain Res Rev. 2000; 32:163–6.

18. Madariaga J, Fromowitz F, Phillips M, Hoover HC Jr. Squamous cell carcinoma in congenital ichthyosis with deafness and keratitis. A case report and review of the literature. Cancer. 1986; 57:2026–9.

19. Walcott B, moore LC, Birzgalis A. . Role of gap junctions in fluid secretion of lacrimal glands. Am J Physiol Cell Physiol. 2002; 282:501–7.

20. Wiszniewski L, Limat A, Saurat JH. . Differential expression if connexins during stratification of human keratinocytes. J Invest Dermatol. 2000; 115:278–85.

21. Hernandez Galindo EE, Theiss C, Steuhl KP, Meller D. Gap junctional communication in microinjected human limbal and peripheral corneal epithelial cells cultured on intact amniotic membrane. Exp Eye Res. 2003; 76:303–14.

22. Derse M, Wannke E, Payer H. . Successful topical cyclosporine. A in the therapy of progressive vascularising keratitis in keratitis-ichthyosis-deafness (KID) syndrome (Senter syndrome) [in German]. Klin Monatsbl Augenheilkd. 2002; 219:383–6.

23. Carey AB, Burke WA, Park HM. Malignant fibrous histiocytoma in keratosis, ichthyosis, and deafness syndrome. J Am Acad Dermatol. 1998; 19:1124–6.