BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by the association of skin lesions, hearing loss and vascularizing keratitis. KID syndrome is caused by autosomal dominant mutations in the connexin 26 gene (GJB2). OBJECTIVES: To establish whether there is a correlation between genotype and phenotype in KID syndrome. METHODS: Clinical examination and molecular analysis of GJB2 were performed in a cohort of 14 patients with KID syndrome originating from 11 families. We also reviewed the 23 cases with molecular analysis previously reported in the literature. RESULTS: The patients displayed the classical signs of KID syndrome with the additional finding of inflammatory nodules in six patients (43%); this clinical finding has not been described previously in the literature. One patient presented at the age of 18 years with a fatal carcinoma of the tongue, an extremely rare reported complication. For seven of the 11 families (64%) the disease was sporadic, whereas it was familial in the remaining four families (36%). Twelve patients (86%) were heterozygous for the p.Asp50Asn mutation and two patients (14%) were heterozygous for the p.Ser17Phe mutation. Surprisingly, a family in which we personally examined the healthy parents had two affected children heterozygous for the p.Asp50Asn mutation, suggesting germinal mosaicism. Compared with patients with the p.Asp50Asn mutation, the two patients with the p.Ser17Phe mutation had more severe skin involvement. One of these two patients experienced a carcinoma of the tongue. CONCLUSIONS: Familial cases appear to be more frequent than reported in the literature. The possibility of germinal mosaicism must be taken into account for genetic counselling. This study also suggests that patients with the p.Ser17Phe mutation may have a more severe phenotype and could be at higher risk for tongue carcinoma.
BACKGROUND:Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by the association of skin lesions, hearing loss and vascularizing keratitis. KID syndrome is caused by autosomal dominant mutations in the connexin 26 gene (GJB2). OBJECTIVES: To establish whether there is a correlation between genotype and phenotype in KID syndrome. METHODS: Clinical examination and molecular analysis of GJB2 were performed in a cohort of 14 patients with KID syndrome originating from 11 families. We also reviewed the 23 cases with molecular analysis previously reported in the literature. RESULTS: The patients displayed the classical signs of KID syndrome with the additional finding of inflammatory nodules in six patients (43%); this clinical finding has not been described previously in the literature. One patient presented at the age of 18 years with a fatal carcinoma of the tongue, an extremely rare reported complication. For seven of the 11 families (64%) the disease was sporadic, whereas it was familial in the remaining four families (36%). Twelve patients (86%) were heterozygous for the p.Asp50Asn mutation and two patients (14%) were heterozygous for the p.Ser17Phe mutation. Surprisingly, a family in which we personally examined the healthy parents had two affected children heterozygous for the p.Asp50Asn mutation, suggesting germinal mosaicism. Compared with patients with the p.Asp50Asn mutation, the two patients with the p.Ser17Phe mutation had more severe skin involvement. One of these two patients experienced a carcinoma of the tongue. CONCLUSIONS: Familial cases appear to be more frequent than reported in the literature. The possibility of germinal mosaicism must be taken into account for genetic counselling. This study also suggests that patients with the p.Ser17Phe mutation may have a more severe phenotype and could be at higher risk for tongue carcinoma.
Authors: Ming Yang Lee; Hong-Zhan Wang; Thomas W White; Tony Brooks; Alan Pittman; Heerni Halai; Anastasia Petrova; Diane Xu; Stephen L Hart; Veronica A Kinsler; Wei-Li Di Journal: J Invest Dermatol Date: 2019-11-06 Impact factor: 8.551
Authors: Evelyn Lilly; Christopher G Bunick; Alexander M Maley; Shali Zhang; Mary K Spraker; Amy J Theos; Karina L Vivar; Lucia Seminario-Vidal; Adam E Bennett; Robert Sidbury; Yasushi Ogawa; Masashi Akiyama; Barbara Binder; Smail Hadj-Rabia; Raffaella A Morotti; Earl J Glusac; Keith A Choate; Gabriele Richard; Leonard M Milstone Journal: J Am Acad Dermatol Date: 2018-10-02 Impact factor: 11.527
Authors: Pallavi V Mhaske; Noah A Levit; Leping Li; Hong-Zhan Wang; Jack R Lee; Zunaira Shuja; Peter R Brink; Thomas W White Journal: Am J Physiol Cell Physiol Date: 2013-02-27 Impact factor: 4.249