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Palmoplantar keratoderma in a patient with a chromosome 12q deletion
P1303
P1305
A novel TAP2 mutation leading to the absence of HLA class I is responsible for a neoplastic degeneration over previous skin lesion ˜ a, MD, Department of Dermatology, University Clinic of Navarra, Agustin Espan Pamplona, Navarra, Spain; Oscar De La Calle, PhD, Department of Immunology, San Pablo Hospital, Barcelona, Spain; Laura Martinez, PhD, Department of Immunology, San Pablo Hospital, Barcelona, Spain; Celia Gonzalez, PhD, Department of Immunology, San Pablo Hospital, Barcelona, Spain Introduction: Bare lymphocyte syndrome (BLS) is characterized by a severe downregulation of HLA class I (BLS type I) or class II molecules (BLS type II). To date, 16 cases of HLA I class deficiency have been described. Patients with TAP deficiencies are usually characterized by respiratory chronic bacterial infections, and features of a chronic granulomatous inflammation. Herein, we present a new case of BLS type I, with a novel TAP2 mutation which has not been described previously, associated with a neoplastic degeneration over previous skin lesions.
Incontinentia pigmenti in three generations: A case report Elizabeth Clemons, Louisiana State University Health Sciences Center, Shreveport, LA, United States; David Clemons, MD, Dermatology and Skin Surgery, Shreveport, LA, United States; J. Anthony Lee, MD, The Delta Pathology Group, Shreveport, LA, United States; Seth Berney, MD, Louisiana State University Health Sciences Center, Shreveport, LA, United States
Case report: A 46-year-old female presented with a history of severe bronchiectasis and skin ulcers on the right leg with necrotizing granulomatous lesions since the age of 10. Tuberculosis and fungus infections were ruled out. An aggressive form of squamous cell carcinoma over previous ulcerated skin lesions on right leg was developed, leading to the right leg amputation. The patient relapsed with liver, lung and bone metastasis, and she died 4 months later. An HLA I class deficiency and HLA II class conserved expression were observed in the patient. The patient was homozygous for all the HLA loci, suggesting consanguinity. Sequencing of the full length TAP1 and TAP2 complementary DNAs (cDNA) showed a single point mutation at nucleotide 628, C to G, placed at exon 3 of the TAP2 gene. This mutation converts the arginine 210 into a premature stop codon. The relatives (the mother and three daughters) were heterozygous for the mutation and the HLA haplotype. Discussion: TAP down-regulation in neoplasias has been reported in many studies and could be related with the emergence of immune escape of tumors. HLA class I deficient patients usually shown chronic bacterial infections of the respiratory tract and severe chronic cutaneous granulomatous lesions. In this report, we described for the first time the development of neoplastic disease over previous TAP-related lesions.
Incontinentia pigmenti (IP), also known as BlocheSulzberger syndrome, is a rare, Xlinked dominant genodermatosis caused by a mutation of the nuclear factor kappa B essential modulator (NEMO) gene which is an essential component to many immune, inflammatory, and apoptotic pathways. This mutation represents a lethal defect in the majority of male fetuses; however, it is variably expressed in females. The cutaneous manifestations of IP typically evolve through four successive, yet overlapping stages: vesiculobullous, veruccous, hyperpigmented, and atrophic. Other commonly affected sites include the eyes, hair, teeth, and central nervous system. The major causes of morbidity and mortality are related to neurologic and ophthalmologic sequelae including seizures, mental retardation, and visual impairment. We describe the case of a 9-day-old female infant who presented with the classic vesiculobullous skin lesions involving the trunk and extremities. A biopsy of the infant’s skin rash revealed eosinophilic spongiosis, vesiculation, and dyskeratotic keratinocytes consistent with IP. Bacterial cultures and herpes simplex PCR of the lesions were negative. Magnetic resonance imaging of the brain was interpreted as focal gyral edema with peripheral enhancement representative of focal cortical necrosis. Further questioning of the patient’s mother and maternal grandmother indicated that they had similar, undiagnosed perinatal skin conditions. Examination of the patient’s mother demonstrated linear, atrophic skin lesions located predominantly over the extremities, and the maternal grandmother was found to have persistent brown macules in her axillae in addition to abnormal dentition also consistent with IP. The patient later experienced developmental delays and a seizure disorder. This case illustrates in three successive generations the various physical findings at different stages of the rare genetic disease of IP. Commercial support: None identified.
Commercial support: None identified.
P1304 Dyskeratosis congenita, a case report with late onset bone marrow hypoplasia Dan R. Lo´pez-Garcı´a, MD, Servicio de Dermatologı´a, Hospital Universitario, U.A.N.L., Mty, N.L., Mexico; Claudia I. Ancer-Arellano, Ma. del Carmen Liy Wong, MD, Servicio de Dermatologı´a, Hospital Universitario, MTY, N.L., Mexico; Minerva Go´mez-Flores, MD, Servicio de Dermatologı´a, Hospital Universitario, MTY, N.L., Mexico; Jorge Ocampo-Candiani, MD, Servicio de Dermatologı´a, Hospital Universitario, MTY, N.L., Mexico Background: Dyskeratosis congenita (DC) is a rare disorder characterized by a classical tetrad of progressive bone marrow failure, reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia. DC is predominantly inherited in an Xlinked recessive form. The gene responsible, DKC1 located at Xq28, encodes for a dyskeratin that is believed to be essential in ribosome biogenesis and telomerase assembly. Early mortality is often associated with bone marrow failure. Case report: A 29-year-old male, who noted since early infancy the presence of a generalized skin disorder that affected the scalp, oral mucosa, nails, and skin folds predominantly. Physical examination revealed a marked mottled and reticulate hyperpigmentation of the face, neck, arms, and legs, sparing the trunk. Poikilodermatous changes with atrophy and telangiectasia in seborrheic regions was found, along with xerosis scarring alopecic patches on the scalp. Twenty nail dystrophy and leukoplakia was noted on the tonge and oral mucosa. The patient had a medical history of moderate tobacco consumption, photosensitivity, and esophageal dilations. A month before the first visit to our department, the patient was seen by a hematologist because of fatigue; the CBC revealed moderate pancytopenia, and a bone marrow biopsy showed hypoplasia. Skin biopsy was compatible with dyskeratosis congenita. The patient was advised to continue close follow-up at the hematology clinic. Discussion: DC is a rare genodermatosis; approximately 200 cases are reported in the literature. The vast majority of cases are diagnosed during childhood, and 70% of patients die directly from bone marrow failure at a median age of 16 years. The interesting features of this case are the late presentation of bone marrow failure and the delay in diagnosis. Management strategies should include photoprotection, smoking cessation, surveillance of leukoplakia, and close hematologic follow-up. The success rate of BMT is limited because of a high prevalence of fatal pulmonary complications which likely reflect preexisting pulmonary disease in these patients. DNA testing of the genes responsible for the X-linked and autosomal dominant forms of DC allows us to perform prenatal testing, early diagnosis via postnatal testing (which may, in turn, enable harvesting of the patient’s bone marrow before marrow failure), and carrier detection. Gene therapy may be a promising future treatment modality for this potentially fatal disease. Commercial support: None identified.
AB80
J AM ACAD DERMATOL
P1306 Palmoplantar keratoderma in a patient with a chromosome 12q deletion Ronald Vender, MD, Dermatrials Research, Hamilton, ON, Canada; Ian MacDougall, Michael C. DeGroote School of Medicine, Hamilton, ON, Canada Keratins are a group of proteins that form the intermediate filament cytoskeleton that is essential in providing structural integrity to the skin. These proteins can be broadly classified into type I and type II keratins, which are encoded on two dense clusters on chromosome 17q and 12q, respectively. Disruptions of these genes may result in a heterogeneous group of diseases characterized by marked thickening of the epidermis of the palms and soles. Past reports have described patients with deletions, translocations and ring formation of chromosome 12. We report the case of a 9-year-old boy with a de novo interstitial deletion of the long arm of chromosome 12: 46,XY,del(12)(Q24.31Q24.33) presenting with palmoplantar keratoderma. Commercial support: None identified.
FEBRUARY 2008
P1305
A novel TAP2 mutation leading to the absence of HLA class I is responsible for a neoplastic degeneration over previous skin lesion ˜ a, MD, Department of Dermatology, University Clinic of Navarra, Agustin Espan Pamplona, Navarra, Spain; Oscar De La Calle, PhD, Department of Immunology, San Pablo Hospital, Barcelona, Spain; Laura Martinez, PhD, Department of Immunology, San Pablo Hospital, Barcelona, Spain; Celia Gonzalez, PhD, Department of Immunology, San Pablo Hospital, Barcelona, Spain Introduction: Bare lymphocyte syndrome (BLS) is characterized by a severe downregulation of HLA class I (BLS type I) or class II molecules (BLS type II). To date, 16 cases of HLA I class deficiency have been described. Patients with TAP deficiencies are usually characterized by respiratory chronic bacterial infections, and features of a chronic granulomatous inflammation. Herein, we present a new case of BLS type I, with a novel TAP2 mutation which has not been described previously, associated with a neoplastic degeneration over previous skin lesions.
Incontinentia pigmenti in three generations: A case report Elizabeth Clemons, Louisiana State University Health Sciences Center, Shreveport, LA, United States; David Clemons, MD, Dermatology and Skin Surgery, Shreveport, LA, United States; J. Anthony Lee, MD, The Delta Pathology Group, Shreveport, LA, United States; Seth Berney, MD, Louisiana State University Health Sciences Center, Shreveport, LA, United States
Case report: A 46-year-old female presented with a history of severe bronchiectasis and skin ulcers on the right leg with necrotizing granulomatous lesions since the age of 10. Tuberculosis and fungus infections were ruled out. An aggressive form of squamous cell carcinoma over previous ulcerated skin lesions on right leg was developed, leading to the right leg amputation. The patient relapsed with liver, lung and bone metastasis, and she died 4 months later. An HLA I class deficiency and HLA II class conserved expression were observed in the patient. The patient was homozygous for all the HLA loci, suggesting consanguinity. Sequencing of the full length TAP1 and TAP2 complementary DNAs (cDNA) showed a single point mutation at nucleotide 628, C to G, placed at exon 3 of the TAP2 gene. This mutation converts the arginine 210 into a premature stop codon. The relatives (the mother and three daughters) were heterozygous for the mutation and the HLA haplotype. Discussion: TAP down-regulation in neoplasias has been reported in many studies and could be related with the emergence of immune escape of tumors. HLA class I deficient patients usually shown chronic bacterial infections of the respiratory tract and severe chronic cutaneous granulomatous lesions. In this report, we described for the first time the development of neoplastic disease over previous TAP-related lesions.
Incontinentia pigmenti (IP), also known as BlocheSulzberger syndrome, is a rare, Xlinked dominant genodermatosis caused by a mutation of the nuclear factor kappa B essential modulator (NEMO) gene which is an essential component to many immune, inflammatory, and apoptotic pathways. This mutation represents a lethal defect in the majority of male fetuses; however, it is variably expressed in females. The cutaneous manifestations of IP typically evolve through four successive, yet overlapping stages: vesiculobullous, veruccous, hyperpigmented, and atrophic. Other commonly affected sites include the eyes, hair, teeth, and central nervous system. The major causes of morbidity and mortality are related to neurologic and ophthalmologic sequelae including seizures, mental retardation, and visual impairment. We describe the case of a 9-day-old female infant who presented with the classic vesiculobullous skin lesions involving the trunk and extremities. A biopsy of the infant’s skin rash revealed eosinophilic spongiosis, vesiculation, and dyskeratotic keratinocytes consistent with IP. Bacterial cultures and herpes simplex PCR of the lesions were negative. Magnetic resonance imaging of the brain was interpreted as focal gyral edema with peripheral enhancement representative of focal cortical necrosis. Further questioning of the patient’s mother and maternal grandmother indicated that they had similar, undiagnosed perinatal skin conditions. Examination of the patient’s mother demonstrated linear, atrophic skin lesions located predominantly over the extremities, and the maternal grandmother was found to have persistent brown macules in her axillae in addition to abnormal dentition also consistent with IP. The patient later experienced developmental delays and a seizure disorder. This case illustrates in three successive generations the various physical findings at different stages of the rare genetic disease of IP. Commercial support: None identified.
Commercial support: None identified.
P1304 Dyskeratosis congenita, a case report with late onset bone marrow hypoplasia Dan R. Lo´pez-Garcı´a, MD, Servicio de Dermatologı´a, Hospital Universitario, U.A.N.L., Mty, N.L., Mexico; Claudia I. Ancer-Arellano, Ma. del Carmen Liy Wong, MD, Servicio de Dermatologı´a, Hospital Universitario, MTY, N.L., Mexico; Minerva Go´mez-Flores, MD, Servicio de Dermatologı´a, Hospital Universitario, MTY, N.L., Mexico; Jorge Ocampo-Candiani, MD, Servicio de Dermatologı´a, Hospital Universitario, MTY, N.L., Mexico Background: Dyskeratosis congenita (DC) is a rare disorder characterized by a classical tetrad of progressive bone marrow failure, reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia. DC is predominantly inherited in an Xlinked recessive form. The gene responsible, DKC1 located at Xq28, encodes for a dyskeratin that is believed to be essential in ribosome biogenesis and telomerase assembly. Early mortality is often associated with bone marrow failure. Case report: A 29-year-old male, who noted since early infancy the presence of a generalized skin disorder that affected the scalp, oral mucosa, nails, and skin folds predominantly. Physical examination revealed a marked mottled and reticulate hyperpigmentation of the face, neck, arms, and legs, sparing the trunk. Poikilodermatous changes with atrophy and telangiectasia in seborrheic regions was found, along with xerosis scarring alopecic patches on the scalp. Twenty nail dystrophy and leukoplakia was noted on the tonge and oral mucosa. The patient had a medical history of moderate tobacco consumption, photosensitivity, and esophageal dilations. A month before the first visit to our department, the patient was seen by a hematologist because of fatigue; the CBC revealed moderate pancytopenia, and a bone marrow biopsy showed hypoplasia. Skin biopsy was compatible with dyskeratosis congenita. The patient was advised to continue close follow-up at the hematology clinic. Discussion: DC is a rare genodermatosis; approximately 200 cases are reported in the literature. The vast majority of cases are diagnosed during childhood, and 70% of patients die directly from bone marrow failure at a median age of 16 years. The interesting features of this case are the late presentation of bone marrow failure and the delay in diagnosis. Management strategies should include photoprotection, smoking cessation, surveillance of leukoplakia, and close hematologic follow-up. The success rate of BMT is limited because of a high prevalence of fatal pulmonary complications which likely reflect preexisting pulmonary disease in these patients. DNA testing of the genes responsible for the X-linked and autosomal dominant forms of DC allows us to perform prenatal testing, early diagnosis via postnatal testing (which may, in turn, enable harvesting of the patient’s bone marrow before marrow failure), and carrier detection. Gene therapy may be a promising future treatment modality for this potentially fatal disease. Commercial support: None identified.
AB80
J AM ACAD DERMATOL
P1306 Palmoplantar keratoderma in a patient with a chromosome 12q deletion Ronald Vender, MD, Dermatrials Research, Hamilton, ON, Canada; Ian MacDougall, Michael C. DeGroote School of Medicine, Hamilton, ON, Canada Keratins are a group of proteins that form the intermediate filament cytoskeleton that is essential in providing structural integrity to the skin. These proteins can be broadly classified into type I and type II keratins, which are encoded on two dense clusters on chromosome 17q and 12q, respectively. Disruptions of these genes may result in a heterogeneous group of diseases characterized by marked thickening of the epidermis of the palms and soles. Past reports have described patients with deletions, translocations and ring formation of chromosome 12. We report the case of a 9-year-old boy with a de novo interstitial deletion of the long arm of chromosome 12: 46,XY,del(12)(Q24.31Q24.33) presenting with palmoplantar keratoderma. Commercial support: None identified.
FEBRUARY 2008