- Email: [email protected]
An Indian child with Kindler syndrome resulting from a new homozygous non-sense mutation (C468X) in the KIND1 gene
P1328
P1401
SUNBURN AND QUALITY OF LIFE Pascale Guitera, MD, Hopital St Louis, Paris, France; Charles Taieb, MD, Eric Myon, PhD; Public Health, Quality of Life and Health Economics, Boulogne Billancourt, France; Louis Dubertret, MD, Hopital St Louis, Paris, France
AN INDIAN CHILD WITH KINDLER SYNDROME RESULTING FROM A NEW HOMOZYGOUS NON-SENSE MUTATION (C468X) IN THE KIND1 GENE Sethuraman Gomathy, MD, All India Institute of Medical Sciences, New Delhi, India; Gabrielle Ashton, BSc, GKT Medical School, London, England; Vinod Sharma, MD, All India Institute of Medical Sciences, New Delhi, India; John McGrath, MD, GKT Medical School, London, England Kindler syndrome is an autosomal recessive genodermatosis characterized by acral bullae in infancy and early childhood, progressive poikiloderma, and diffuse cutaneous atrophy. The molecular defect underlying this disorder has been shown to involve loss-of-function mutations in a novel gene, KIND1, encoding the protein kindlin-1, a recently identified 677-amino acid protein involved in anchorage of the actin cytoskeleton to the extracellular matrix. We describe the clinical features of an 11-year-old boy with Kindler syndrome from a consanguineous Indian family and the identification of a homozygous non-sense mutation (C468X) in exon 12 of the KIND1 gene in his genomic DNA. This mutation has not been described previously, but is similar to the 17 previously published KIND1 mutations that are all predicted to lead to loss of kindlin-1 protein expression and function. The clinical features in this boy highlight the relevance of kindlin-1 in skin biology, specifically to epidermal adhesion and response to acute and long-term sun exposure. Delineation of this new pathogenic mutation in KIND1 is also useful for genetic counseling in this family and in assessing carrier status in unaffected family members.
Objective: The ICARE program aims to describe how patients get sunburn and their knowledge of the consequences of sun exposure. Method: Patients suffering sunburn going to their pharmacy for their first treatment were asked to complete a questionnaire that included the DLQI (Dermatological Life Quality Index) and to return it by mail. Tool: The DLQI measures and compares disability in different skin conditions. The higher the score, the more quality of life (QoL) is affected. Results: First results showed evidence of impairment of QoL, with a mean DLQI total score of 4.0. The mean total score for men and women were 2.7 and 4.4 (P \.05), respectively. The mean number of sunburned areas (impacts) was reported; the mean number of impacts was 2.3; patients were allocated according to the number of impacts. For patients with 3 or fewer impacts, the mean DLQI total score was 3.3; for patients with 4 impacts or more, mean DLQI score was 6.8 (P [.0001). Further analysis demonstrated that age did not correlate with the scores. Discussion: Our population reflects QoL impairment compared with the ranges obtained when the DLQI was initially validated; that is, for patients with acne the DLQI mean score was 4.3, 6.7 for patients with viral warts, and 3.4 for patients with solar keratosis (Finlay AY, 1994).Those results confirm the ones obtained during a previous study among pharmacy staff demonstrating a link between QoL impairment and sunburn severity. Educating patients about therapeutic options for sunburn may further patients progress and awareness about the risks of sun exposure.
Nothing to disclose.
50% supported by Avene Laboratory
Genodermatoses P1400 A CHILD WITH BAZEX-DUPRE-CHRISTOL SYNDROME ASSOCIATED WITH MULTIPLE GENITAL TRICHOFOLLICULOMATA Anthony Yung, MBChB, Leeds General Infirmary, Leeds, England; Julia NewtonBishop, MBChB, St James’ Hospital, Leeds, England Bazex-Dupre-Christol syndrome was first described by Bazex in 1964. It is characterized by the triad of congenital hypotrichosis, follicular atrophoderma (often affecting the dorsa of the hands and feet, the face, and extensor surfaces of the elbows or knees), and the development of basocellular neoplasms (including basal cell nevi and basal cell carcinomas). Other commonly reported features include associated hair shaft abnormalities (pili torti, trichorrhexis nodosa), prominent milia affecting the face, and hypohidrosis. Other less consistently reported features include atopic diathesis, comedones, keratosis pilaris, joint hypermobility, lingua plicata, and hyperpigmentation of the forehead. This condition has been postulated to be transmitted by a X-linked dominant gene. The genetic defect has been reported to localize to Xq24-q27 by linkage analysis of microsatellite markers in members of 3 families with the syndrome. We present the case of a 3-year-old girl with Bazex-Dupre-Christol syndrome with features of congenital hypotrichia, prominent facial milia, and follicular atrophoderma. Her mother had similar features of multiple milia and hypotrichosis as a child, follicular atrophoderma, and hidradenitis suppurativa. The child’s maternal grandfather has a phenotype similar to that of her mother. Her maternal greatgrandmother and one of her sisters had similar phenotypes to her mother but without hidradenitis suppurativa; however, both developed multiple basal cell carcinomas starting from the third decade of life. At the 2 years of age, the child developed increasing numbers of multiple brown papules over the genitalia and medial aspects of the thigh. A biopsy specimen from the labial area revealed multiple dermal nodules consisting of interconnecting strands of rounded nests of basaloid cells centered around the hair follicles. These nodules also demonstrated continuity with the epidermis. A loose myxoid stroma without retraction artefact was present surrounding the interconnecting strands of basaloid cells. The histological appearances are consistent with multiple benign trichofolliculomata.
P1402 A RARE EXPRESSION OF GLOMANGIOMA SUGGESTING LOSS OF HETEROZYGOSITY Hana Bak, MD, Won-Soo Lee, MD, PhD, Department of Dermatology, Institute of Hair and Cosmetic Medicine, Yonsei University, Wonju College of Medicine, Wonju, Korea Glomangioma is an uncommon cutaneous affection related to the arterial segment of the cutaneous glomus, the Sucquet-Hoyer canal. Lesions may be solitary or multiple, the latter accounting for fewer than 10% of all cases. Distribution of multiple glomangiomas may be localized or generalized. In the localized type, the lesions are grouped over a limited area but never over the face and trunk, whereas in the generalized type, they may spread diffusely over the body. We found only 13 cases of congenital multiple glomus tumors in literature. The patterns of congenital multiple glomus tumors were very important to analogize the pathogenesis of loss of heterozygosity.
Multiple trichofolliculomata and hidradenitis suppurativa have not been previously described in association with Bazex-Dupre-Christol syndrome. We present a case, discuss the significance of these new findings, and review the literature of this rare syndrome.
A 12-year-old boy presented with erythematous to bluish skin lesions. History disclosed that a few days after birth, multiple, small, erythematous to bluish, slightly raised plaques consisting of papules and dots on the left side of the abdomen and right chest wall began to appear. Family history was not contributory. Histologic examination revealed ectatic lumens within the dermis, which was lined by a few layers of glomus cells embedded in a fibrous stroma. In our case, the distribution was unique and hitherto rarely described. The lesions were on the left side of the abdomen and right chest wall, similar to segmental conditions. This unusual segmental-like manifestation of the lesion suggests loss of heterozygosity at an early stage of embryogenesis. Our case can be regarded as a very typical model in terms of the pathogenesis of glomus tumor.
Nothing to disclose.
Nothing to disclose.
MARCH 2005
J AM ACAD DERMATOL
P109
P1401
SUNBURN AND QUALITY OF LIFE Pascale Guitera, MD, Hopital St Louis, Paris, France; Charles Taieb, MD, Eric Myon, PhD; Public Health, Quality of Life and Health Economics, Boulogne Billancourt, France; Louis Dubertret, MD, Hopital St Louis, Paris, France
AN INDIAN CHILD WITH KINDLER SYNDROME RESULTING FROM A NEW HOMOZYGOUS NON-SENSE MUTATION (C468X) IN THE KIND1 GENE Sethuraman Gomathy, MD, All India Institute of Medical Sciences, New Delhi, India; Gabrielle Ashton, BSc, GKT Medical School, London, England; Vinod Sharma, MD, All India Institute of Medical Sciences, New Delhi, India; John McGrath, MD, GKT Medical School, London, England Kindler syndrome is an autosomal recessive genodermatosis characterized by acral bullae in infancy and early childhood, progressive poikiloderma, and diffuse cutaneous atrophy. The molecular defect underlying this disorder has been shown to involve loss-of-function mutations in a novel gene, KIND1, encoding the protein kindlin-1, a recently identified 677-amino acid protein involved in anchorage of the actin cytoskeleton to the extracellular matrix. We describe the clinical features of an 11-year-old boy with Kindler syndrome from a consanguineous Indian family and the identification of a homozygous non-sense mutation (C468X) in exon 12 of the KIND1 gene in his genomic DNA. This mutation has not been described previously, but is similar to the 17 previously published KIND1 mutations that are all predicted to lead to loss of kindlin-1 protein expression and function. The clinical features in this boy highlight the relevance of kindlin-1 in skin biology, specifically to epidermal adhesion and response to acute and long-term sun exposure. Delineation of this new pathogenic mutation in KIND1 is also useful for genetic counseling in this family and in assessing carrier status in unaffected family members.
Objective: The ICARE program aims to describe how patients get sunburn and their knowledge of the consequences of sun exposure. Method: Patients suffering sunburn going to their pharmacy for their first treatment were asked to complete a questionnaire that included the DLQI (Dermatological Life Quality Index) and to return it by mail. Tool: The DLQI measures and compares disability in different skin conditions. The higher the score, the more quality of life (QoL) is affected. Results: First results showed evidence of impairment of QoL, with a mean DLQI total score of 4.0. The mean total score for men and women were 2.7 and 4.4 (P \.05), respectively. The mean number of sunburned areas (impacts) was reported; the mean number of impacts was 2.3; patients were allocated according to the number of impacts. For patients with 3 or fewer impacts, the mean DLQI total score was 3.3; for patients with 4 impacts or more, mean DLQI score was 6.8 (P [.0001). Further analysis demonstrated that age did not correlate with the scores. Discussion: Our population reflects QoL impairment compared with the ranges obtained when the DLQI was initially validated; that is, for patients with acne the DLQI mean score was 4.3, 6.7 for patients with viral warts, and 3.4 for patients with solar keratosis (Finlay AY, 1994).Those results confirm the ones obtained during a previous study among pharmacy staff demonstrating a link between QoL impairment and sunburn severity. Educating patients about therapeutic options for sunburn may further patients progress and awareness about the risks of sun exposure.
Nothing to disclose.
50% supported by Avene Laboratory
Genodermatoses P1400 A CHILD WITH BAZEX-DUPRE-CHRISTOL SYNDROME ASSOCIATED WITH MULTIPLE GENITAL TRICHOFOLLICULOMATA Anthony Yung, MBChB, Leeds General Infirmary, Leeds, England; Julia NewtonBishop, MBChB, St James’ Hospital, Leeds, England Bazex-Dupre-Christol syndrome was first described by Bazex in 1964. It is characterized by the triad of congenital hypotrichosis, follicular atrophoderma (often affecting the dorsa of the hands and feet, the face, and extensor surfaces of the elbows or knees), and the development of basocellular neoplasms (including basal cell nevi and basal cell carcinomas). Other commonly reported features include associated hair shaft abnormalities (pili torti, trichorrhexis nodosa), prominent milia affecting the face, and hypohidrosis. Other less consistently reported features include atopic diathesis, comedones, keratosis pilaris, joint hypermobility, lingua plicata, and hyperpigmentation of the forehead. This condition has been postulated to be transmitted by a X-linked dominant gene. The genetic defect has been reported to localize to Xq24-q27 by linkage analysis of microsatellite markers in members of 3 families with the syndrome. We present the case of a 3-year-old girl with Bazex-Dupre-Christol syndrome with features of congenital hypotrichia, prominent facial milia, and follicular atrophoderma. Her mother had similar features of multiple milia and hypotrichosis as a child, follicular atrophoderma, and hidradenitis suppurativa. The child’s maternal grandfather has a phenotype similar to that of her mother. Her maternal greatgrandmother and one of her sisters had similar phenotypes to her mother but without hidradenitis suppurativa; however, both developed multiple basal cell carcinomas starting from the third decade of life. At the 2 years of age, the child developed increasing numbers of multiple brown papules over the genitalia and medial aspects of the thigh. A biopsy specimen from the labial area revealed multiple dermal nodules consisting of interconnecting strands of rounded nests of basaloid cells centered around the hair follicles. These nodules also demonstrated continuity with the epidermis. A loose myxoid stroma without retraction artefact was present surrounding the interconnecting strands of basaloid cells. The histological appearances are consistent with multiple benign trichofolliculomata.
P1402 A RARE EXPRESSION OF GLOMANGIOMA SUGGESTING LOSS OF HETEROZYGOSITY Hana Bak, MD, Won-Soo Lee, MD, PhD, Department of Dermatology, Institute of Hair and Cosmetic Medicine, Yonsei University, Wonju College of Medicine, Wonju, Korea Glomangioma is an uncommon cutaneous affection related to the arterial segment of the cutaneous glomus, the Sucquet-Hoyer canal. Lesions may be solitary or multiple, the latter accounting for fewer than 10% of all cases. Distribution of multiple glomangiomas may be localized or generalized. In the localized type, the lesions are grouped over a limited area but never over the face and trunk, whereas in the generalized type, they may spread diffusely over the body. We found only 13 cases of congenital multiple glomus tumors in literature. The patterns of congenital multiple glomus tumors were very important to analogize the pathogenesis of loss of heterozygosity.
Multiple trichofolliculomata and hidradenitis suppurativa have not been previously described in association with Bazex-Dupre-Christol syndrome. We present a case, discuss the significance of these new findings, and review the literature of this rare syndrome.
A 12-year-old boy presented with erythematous to bluish skin lesions. History disclosed that a few days after birth, multiple, small, erythematous to bluish, slightly raised plaques consisting of papules and dots on the left side of the abdomen and right chest wall began to appear. Family history was not contributory. Histologic examination revealed ectatic lumens within the dermis, which was lined by a few layers of glomus cells embedded in a fibrous stroma. In our case, the distribution was unique and hitherto rarely described. The lesions were on the left side of the abdomen and right chest wall, similar to segmental conditions. This unusual segmental-like manifestation of the lesion suggests loss of heterozygosity at an early stage of embryogenesis. Our case can be regarded as a very typical model in terms of the pathogenesis of glomus tumor.
Nothing to disclose.
Nothing to disclose.
MARCH 2005
J AM ACAD DERMATOL
P109