DOCSLIB.ORG

Xeroderma Pigmentosum: an Insight Into DNA Repair Processes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Xeroderma Pigmentosum: an Insight Into DNA Repair Processes ACCME/Disclosures The USCAP requires that anyone in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. Dr. Jennifer O. Black declares she has no conflict(s) of interest to disclose. Xeroderma Pigmentosum: An Insight into DNA Repair Processes Jennifer O. Black, MD Assistant Professor Division of Pediatric Pathology and Laboratory Medicine Children’s Hospital Colorado University of Colorado Anschutz Medical Campus Aurora, Colorado Introduction: Xeroderma Pigmentosum Xeroderma Pigmentosum (XP): • Initially described 1874 • Rare autosomal recessive disorder • Prevalence: 1-45/million, variable ethnic frequency • UV radiation sensitivity disorder characterized by: • Severe skin burning following minimal sun exposure • Early freckling (before 2 years of age) • Skin cancer at an early age Kraemer KH, DiGiovann JJ. Photochemistry and Photobiology 91:452-459, 2015 Introduction: Xeroderma Pigmentosum XP Clinical Spectrum: • Skin Changes: o Early freckling and subsequent checkered pigmentation o Thin, dry, contracted skin o Telangiectasias o Skin cancers: o Squamous cell carcinoma o Basal cell carcinoma o Melanoma Courtesy Dr. Bahig M. Shehata, Children’s Healthcare of Atlanta Introduction: Xeroderma Pigmentosum Squamous Cell Carcinoma Robbins and Cotran Pathologic Basis of Disease. Lazar, Alexander J.F.; Murphy, George F. Pages 1141-1178 Introduction: Xeroderma Pigmentosum Basal Cell Carcinoma Robbins and Cotran Pathologic Basis of Disease. Lazar, Alexander J.F.; Murphy, George F. Pages 1141-1178. Introduction: Xeroderma Pigmentosum Melanoma Pigment Cell & Melanoma Research Volume 27, Issue 3, pages 454-464 Introduction: Xeroderma Pigmentosum Ocular Manifestations of Disease OCULAR ABNORMALITIES Structural Eyelid Abnormalities: Entropion Ectropion* Lagophthalmos Blepharitis Keratinization Loss of Eyelashes Neoplasms of the Ocular Surface Squamous Cell Carcinoma and Eyelids: Basal Cell Carcinoma Ocular Surface Disease and Conjunctivitis Inflammation: Melanosis* Xerosis Corneal Abnormalities: Neovascularization Pterygium Scarring Brooks et al. Ophthalmology. 2013 Jul; 120(7): 1324–1336. Opacification Other: Photophobia * More frequent in patients with non-burning phenotype Introduction: Xeroderma Pigmentosum Neurologic Manifestations of Disease • 24% XP Patients • Progressive Neurologic Degeneration: o Cognitive deterioration o Impaired hearing o Abnormal speech o Areflexia o Progressive ataxia o Spasticity o Peripheral neuropathy • Brain tumors: Glial tumors • Pontine glioma, glioblastoma, spinal cord astrocytoma Anttinen, et al. Brain. 2008 Aug;131:1979-89 Xeroderma Pigmentosum: Disease Pathophysiology Xeroderma Pigmentosum: Pathophysiology BER: Base excision repair NER: Nucleotide excision repair DSBR: Double stranded break repair MMR: Mismatch repair Xeroderma Pigmentosum: Pathophysiology Historical Studies: • XP cells demonstrate UV radiation hypersensitivity (Gartler 1964) • Deficient excision repair observed in cultured XP skin fibroblasts (Cleaver 1968) • Stable DNA photoproducts identified following UV radiation (Setlow 1962), not removed by XP cells ( Setlow 1969, Cleaver and Trosko 1970) • Defective excision repair in XP cells demonstrated in vitro (Reed 1969) and in vivo (Epstein 1970) • Cell fusion studies demonstrated heterogeneity of XP molecular defects ( De Weerd-Kastelein 1972) Fusion of fibroblasts from different XP patients form heterokaryons that demonstrate corrected DNA repair mechanisms. Characterization of different complementation groups, A-G (Kramer 1975, Arase 1979, Keijer 1979) Xeroderma Pigmentosum: Complementation Groups Complementation Gene Normal Protein Function Disease Characteristics Group Protein that assists with DNA unwinding Photosensitivity, poikiloderma, lentigines, skin cancer, XP-A XPA neurodegeneration Helicase involved with DNA unwinding Photosensitivity, poikiloderma, lentigines, skin cancer, XP-B XPB/ERCC3 neurodegeneration XP-C XPC Protein recognizing global genome defects Photosensitivity, poikiloderma, lentigines, skin cancer Helicase involved with DNA unwinding Photosensitivity, poikiloderma, lentigines, skin cancer, XP-D XPD/ERCC2 neurodegeneration, brain tumors Protein recognizing global genome defects Photosensitivity, poikiloderma, lentigines, skin cancer, XP-E XPE/DDB2 neurodegeneration Forms an endonuclease together with ERCC1 that Photosensitivity, poikiloderma, lentigines, skin cancer, XP-F XPF/ERCC4 incises damaged DNA for repair neurodegeneration, brain tumors Endonuclease that incise damaged DNA Photosensitivity, poikiloderma, lentigines, skin cancer, XP-G XPG/ERCC5 neurodegeneration DNA-polymerase eta (pol-eta) which performs Milder photosensitivity and poikiloderma XP-Variant XPV/POLH trans-lesion DNA synthesis past ultraviolet (UV) Xeroderma Pigmentosum: Pathophysiology Nucleotide Excision Repair Pathway DiGiovanna. J Invest Dermatol. 2012 Mar; 132(3): 785–796. Xeroderma Pigmentosum: Pathophysiology DiGiovanna. J Invest Dermatol. 2012 Mar; 132(3): 785–796. Xeroderma Pigmentosum: Overlap Syndromes Gene Normal Protein Function Clinical Syndrome Disease Characteristics XPB/ERCC3 Helicase involved with DNA unwinding XP-B, CS, TTD Photosensitivity, poikiloderma, lentigines, skin cancer, neurodegeneration XPD/ERCC2 Helicase involved with DNA unwinding XP-D, TTD, COFS, CS Photosensitivity, poikiloderma, lentigines, skin cancer, neurodegeneration, brain tumors XPF/ERCC4 Forms an endonuclease together with ERCC1 that incises XP-F, XFE progeroid Photosensitivity, poikiloderma, lentigines, skin cancer, damaged DNA for repair syndrome, Fanconi anemia neurodegeneration, brain tumors ERCC1 Forms an endonuclease together with XPF/ERCC4 that XP, CS, COFS Photosensitivity, poikiloderma, lentigines, skin cancer, incises damaged DNA for repair neurodegeneration CSA/ERCC8 DNA excision repair protein involved in the TCR pathways CS Growth failure, impaired neurodevelopment, photosensitivity, eye disorders, premature aging CSB/ERCC6 DNA excision repair protein involved in the TCR pathway CS, COFS Growth failure, severely impaired neurodevelopment, photosensitivity, eye disorders, premature aging GTF2H5 TTDA protein stabilizes the DNA/protein complex during TTD Brittle hair, intellectual impairment, photosensitivity unwinding of DNA strand for repair TTDN1/C7orf11 Regulates mitosis and cytokinesis TTD Non-photosensitive TTD CS = Cockayne Syndrome; TTD = Trichothiodystrophy; COFS = Cerebro-Oculo-Facio-Skeletal Syndrome Xeroderma Pigmentosum: Overlap Syndromes Trichothiodystrophy (TTD): • Features: • Photosensitivity (with XPD, XPB, TTDA but not TTDN1 mutations) • Abnormal hair • Decreased fertility • Short stature • Ichthyosis • Normal skin pigmentation • Intellectual impairment without neurodegeneration • Neuroimaging: demyelination, cortical heterotopia, partial agenesis of the corpus callosum, perimedullary fibrosis of the spinal cord, intracranial calcifications DiGiovanna. J Invest Dermatol. 2012 Mar; 132(3): 785–796. Xeroderma Pigmentosum: Overlap Syndromes Cockayne Syndrome (CS) • Results from mutations in the CSA and CSB genes of the NER pathway • Features: • Short stature • Microcephaly • Pigmentary retinal degeneration • Kyphoscoliosis • Gait defects • Sensorineural deafness • Distinct facial features (deep-set eyes, prominent ears, “wizened appearance”) • Neurodegenerative Features; Demyelination (increased DTRs), • Neuroimaging: cerebral atrophy, ventricular dilation, calcification of basal ganglia and cortex, neuronal loss • Multiple Types: • Type I: moderate phenotype, normal prenatal development, abnormalities evident in first 2 years of life • Type II: Severe phenotype, growth failure at birth, death first decade • Type III: Mild symptoms, late onset; photosensitivity with normal pigmentation, no increased risk of cutaneous malignancy Laugel. Mechanisms of Ageing and Development 134 (2013) 161–170 Xeroderma Pigmentosum: Overlap Syndromes Cerebro-Oculo-Facio-Skeletal Syndrome (COFS): • Autosomal recessive disorder\ • Mutations involve CSB, XPD, XPG, and ERCC1 genes • Features: • Microcephaly • Congenital cataracts • Arthrogryposis • Severe developmental delay • Severe postnatal growth failure • Photosensitivity • Facial dysmorphism (prominent nasal root and overhanging upper lip) Laugel. J Med Genet 2008;45:564-571 Xeroderma Pigmentosum Disease Course Xeroderma Pigmentosum: Long Term Survival Leading Cause of Death: Skin cancer and metastasis Lifetime Cancer Risk: • 33% XP patients do not develop cancer • Squamous Cell and Basal Cell Carcinoma: o Median age at first cancer = 9 years (range 1-32 years) o XP patients have 58-year reduction in age at first non-melanocytic skin cancer o 10,000 fold lifetime risk compared to general population • Melanoma: o Median age at first cancer = 22 years (range 2-47 years) o XP patients have a 33-year reduction in age at first non-melanocytic skin cancer o 2,000 fold lifetime risk compared to general population o PTEN mutations more common (53%) compared to general population (16%) • Other Cancer: • Increased risk of lung cancer in XP smokers • Brain tumors Neurodegeneration: • More common in XPA, XPB, XPD, XPF, XPG (Rare in XPC, XPE) • Associated with decreased median age of death compared to XP patients without neurodegeneration (29 vs 37 years) • Second leading cause of death in XP patients
Load more

Recommended publications
  • Open Full Page
    CCR PEDIATRIC ONCOLOGY SERIES CCR Pediatric Oncology Series Recommendations for Childhood Cancer Screening and Surveillance in DNA Repair Disorders Michael F. Walsh1, Vivian Y. Chang2, Wendy K. Kohlmann3, Hamish S. Scott4, Christopher Cunniff5, Franck Bourdeaut6, Jan J. Molenaar7, Christopher C. Porter8, John T. Sandlund9, Sharon E. Plon10, Lisa L. Wang10, and Sharon A. Savage11 Abstract DNA repair syndromes are heterogeneous disorders caused by around the world to discuss and develop cancer surveillance pathogenic variants in genes encoding proteins key in DNA guidelines for children with cancer-prone disorders. Herein, replication and/or the cellular response to DNA damage. The we focus on the more common of the rare DNA repair dis- majority of these syndromes are inherited in an autosomal- orders: ataxia telangiectasia, Bloom syndrome, Fanconi ane- recessive manner, but autosomal-dominant and X-linked reces- mia, dyskeratosis congenita, Nijmegen breakage syndrome, sive disorders also exist. The clinical features of patients with DNA Rothmund–Thomson syndrome, and Xeroderma pigmento- repair syndromes are highly varied and dependent on the under- sum. Dedicated syndrome registries and a combination of lying genetic cause. Notably, all patients have elevated risks of basic science and clinical research have led to important in- syndrome-associated cancers, and many of these cancers present sights into the underlying biology of these disorders. Given the in childhood. Although it is clear that the risk of cancer is rarity of these disorders, it is recommended that centralized increased, there are limited data defining the true incidence of centers of excellence be involved directly or through consulta- cancer and almost no evidence-based approaches to cancer tion in caring for patients with heritable DNA repair syn- surveillance in patients with DNA repair disorders.
    [Show full text]
  • EXTENDED CARRIER SCREENING Peace of Mind for Planned Pregnancies
    Focusing on Personalised Medicine EXTENDED CARRIER SCREENING Peace of Mind for Planned Pregnancies Extended carrier screening is an important tool for prospective parents to help them determine their risk of having a child affected with a heritable disease. In many cases, parents aren’t aware they are carriers and have no family history due to the rarity of some diseases in the general population. What is covered by the screening? Genomics For Life offers a comprehensive Extended Carrier Screening test, providing prospective parents with the information they require when planning their pregnancy. Extended Carrier Screening has been shown to detect carriers who would not have been considered candidates for traditional risk- based screening. With a simple mouth swab collection, we are able to test for over 419 genes associated with inherited diseases, including Fragile X Syndrome, Cystic Fibrosis and Spinal Muscular Atrophy. The assay has been developed in conjunction with clinical molecular geneticists, and includes genes listed in the NIH Genetic Test Registry. For a list of genes and disorders covered, please see the reverse of this brochure. If your gene of interest is not covered on our Extended Carrier Screening panel, please contact our friendly team to assist you in finding a gene test panel that suits your needs. Why have Extended Carrier Screening? Extended Carrier Screening prior to pregnancy enables couples to learn about their reproductive risk and consider a complete range of reproductive options, including whether or not to become pregnant, whether to use advanced reproductive technologies, such as preimplantation genetic diagnosis, or to use donor gametes.
    [Show full text]
  • Disease Reference Book
    The Counsyl Foresight™ Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.counsyl.com | [email protected] | (888) COUNSYL The Counsyl Foresight Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia .................................................................................................................................................................................... 8 21-hydroxylase-deficient Congenital Adrenal Hyperplasia ...........................................................................................................................................................................................10 6-pyruvoyl-tetrahydropterin Synthase Deficiency ..........................................................................................................................................................................................................12 ABCC8-related Hyperinsulinism........................................................................................................................................................................................................................................ 14 Adenosine Deaminase Deficiency .................................................................................................................................................................................................................................... 16 Alpha Thalassemia.............................................................................................................................................................................................................................................................
    [Show full text]
  • Melasma on the Nape of the Neck in a Man
    Letters to the Editor 181 Melasma on the Nape of the Neck in a Man Ann A. Lonsdale-Eccles and J. A. A. Langtry Sunderland Royal Hospital, Kayll Road, Sunderland SR4 7TP, UK. E-mail: [email protected] Accepted July 19, 2004. Sir, sunlight and photosensitizing agents may be more We report a 47-year-old man with light brown macular relevant. pigmentation on the nape of his neck (Fig. 1). It was The differential diagnosis for pigmentation at this site asymptomatic and had developed gradually over 2 years. includes Riehl’s melanosis, Berloque dermatitis and He worked outdoors as a pipe fitter on an oilrig module; poikiloderma of Civatte. Riehl’s melanosis typically however, he denied exposure at this site because he involves the face with a brownish-grey pigmentation; always wore a shirt with a collar that covered the biopsy might be expected to show interface change and affected area. However, on further questioning it liquefaction basal cell degeneration with a moderate transpired that he spent most of the day with his head lymphohistiocytic infiltrate, melanophages and pigmen- bent forward. This reproducibly exposed the area of tary incontinence in the upper dermis. It is usually pigmentation with a sharp cut off inferiorly at the level associated with cosmetic use and may be considered of his collar. He used various shampoos, aftershaves and synonymous with pigmented allergic contact dermatitis shower gels, but none was applied directly to that area. of the face (6, 7). Berloque dermatitis is considered to be His skin was otherwise normal and there was no family caused by a photoirritant reaction to bergapentin; it history of abnormal pigmentation.
    [Show full text]
  • Poikiloderma of Civatte, Slapped Neck Solar Melanosis, Basal Melanin Stores
    American Journal of Dermatology and Venereology 2019, 8(1): 8-13 DOI: 10.5923/j.ajdv.20190801.03 Slapped Neck Solar Melanosis: Is It a New Entity or a Variant of Poikiloderma of Civatte?? (Clinical and Histopathological Study) Khalifa E. Sharquie1,*, Adil A. Noaimi2, Ansam B. Kaftan3 1Department of Dermatology, College of Medicine, University of Baghdad 2Iraqi and Arab Board for Dermatology and Venereology, Dermatology Center, Medical City, Baghdad, Iraq 3Dermatology Center, Medical City, Baghdad, Iraq Abstract Background: Poikiloderma of Civatte although is a common complaint among population, especially European, still it was not reported in dark skin people as in Iraqi population. Objectives: To study all the clinical and histopathological features of Poikiloderma of Civatte in Iraqi population. Patients and Methods: This study is descriptive, clinical and histopathological study. It was carried out at the Dermatology Center, Medical City, Baghdad, Iraq, from September 2017 to October 2018. Thirty-one patients with Poikiloderma of Civatte were included and evaluated by history, physical examination, Wood’s light examination. Lesional skin biopsies were obtained from 9 patients, with histological examination of the sections stained with Hematoxylin and Eosin (H&E) and Fontana-Masson stain. Results: Thirty-one patients were included in this study, with mean age +/- SD was 53.32+/-10 years, and all patients were males. Twenty-six patients (84%) were with skin phenotype III&IV, The pigmentation was either mainly erythematous (22.5%), mainly dark brown pigmentation (29%), and mixed type of pigmentation (48.5%). These lesions were distributed on the sides of the neck and the face and the V shaped area of the chest.
    [Show full text]
  • Blueprint Genetics Ectodermal Dysplasia Panel
    Ectodermal Dysplasia Panel Test code: DE0401 Is a 25 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of ectodermal dysplasia (hidrotic or hypohidrotic) or Ellis-van Creveld syndrome. About Ectodermal Dysplasia Ectodermal Dysplasia (ED) is a group of closely related conditions of which more than 150 different syndromes have been identified. EDs affects the development or function of teeth, hair, nails and sweat glands. ED may present as isolated or as part of a syndromic disease and is commonly subtyped according to sweating ability. The clinical features of the X-linked and autosomal forms of hypohidrotic ectodermal dysplasia (HED) can be indistinguishable and many of the involved genes may lead to phenotypically distinct outcomes depending on number of defective alleles. The most common EDs are hypohidrotic ED and hydrotic ED. X-linked hypohidrotic ectodermal dysplasia (HED) is caused by EDA mutations and explain 75%-95% of familial HED and 50% of sporadic cases. HED is characterized by three cardinal features: hypotrichosis (sparse, slow-growing hair and sparse/missing eyebrows), reduced sweating and hypodontia (absence or small teeth). Reduced sweating poses risk for episodes of hyperthermia. Female carriers may have some degree of hypodontia and mild hypotrichosis. Isolated dental phenotypes have also been described. Mutations in WNT10A have been reported in up to 9% of individuals with HED and in 25% of individuals with HED who do not have defective EDA. Approximately 50% of individuals with heterozygous WNT10A mutation have HED and the most consistent clinical feature is severe oligodontia of permanent teeth.
    [Show full text]
  • Xeroderma Pigmentosum
    Xeroderma pigmentosum Description Xeroderma pigmentosum, which is commonly known as XP, is an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight. This condition mostly affects the eyes and areas of skin exposed to the sun. Some affected individuals also have problems involving the nervous system. The signs of xeroderma pigmentosum usually appear in infancy or early childhood. Many affected children develop a severe sunburn after spending just a few minutes in the sun. The sunburn causes redness and blistering that can last for weeks. Other affected children do not get sunburned with minimal sun exposure, but instead tan normally. By age 2, almost all children with xeroderma pigmentosum develop freckling of the skin in sun-exposed areas (such as the face, arms, and lips); this type of freckling rarely occurs in young children without the disorder. In affected individuals, exposure to sunlight often causes dry skin (xeroderma) and changes in skin coloring (pigmentation). This combination of features gives the condition its name, xeroderma pigmentosum. People with xeroderma pigmentosum have a greatly increased risk of developing skin cancer. Without sun protection, about half of children with this condition develop their first skin cancer by age 10. Most people with xeroderma pigmentosum develop multiple skin cancers during their lifetime. These cancers occur most often on the face, lips, and eyelids. Cancer can also develop on the scalp, in the eyes, and on the tip of the tongue. Studies suggest that people with xeroderma pigmentosum may also have an increased risk of other types of cancer, including brain tumors.
    [Show full text]
  • Trichothiodystrophy
    Trichothiodystrophy Author: Doctor Alfredo Rossi1 and Doctor C. Cantisani. Creation date: June 2004 Scientific Editor: Prof Antonella Tosti 1Dipartimento di Malattie Cutanee-Veneree Chirurgia Plastica-Ricostruttiva, Università degli studi di Roma “La Sapienza” Abstract Keywords Definition Epidemiology Etiology Clinical description Diagnostic methods Prenatal diagnosis Management References Abstract Trichothiodystrophy (TTD) is a rare autosomal recessive genetic disorder characterized by abnormal synthesis of the sulphur containing keratins and consequently hair dysplasia, associated with numerous symptoms affecting mainly organs derived from the neuroectoderm. This phenotypic aspect is due to mutations in the DNA-dependent ATPase/helicase subunit of TFIIH, XPB and XPD. Abnormalities in excision repair of ultraviolet (UV)-damaged DNA are recognized in about half of the patients. The clinical appearance is characterized by brittle and fragile hair, congenital ichthyosis, nail and dental dysplasias, cataract, progeria-like face, growth and mental retardation. The abnormalities are usually obvious at birth, with variable clinical expression. The variants of TTD, depending on their different associations, are known by the initials BIDS, IBIDS, PIBIDS, SIBIDS, ONMRS, as well as the eponyms of the Pollit, Tay, Sabinas syndromes or Amish brittle hair. The exact prevalence of TTD is unknown, but appears to be rather uncommon. About 20 cases of PIBI(D)S have been reported in the literature. Up to 1991, clinical data of 15 cases with IBIDS were published. Prenatal diagnostic of TTD is available. There is no specific treatment. Keywords Brittle hair, photosensitivity, ichthyosis, BIDS, IBIDS, PIBIDS, SIBIDS, ONMRS, Tay-syndrome Definition tail pattern). They named it Trichothiodystrophy, Trichothiodystrophy (TTD) is a group of rare noticing also an increased Photosensitivity and autosomal recessive disorders with heterogenic Ichthyosis in these patients (PIBIDS).
    [Show full text]
  • Predisposition to Hematologic Malignancies in Patients With
    LETTERS TO THE EDITOR carcinomas but no internal cancer by the age of 29 years Predisposition to hematologic malignancies in and 9 years, respectively. patients with xeroderma pigmentosum Case XP540BE . This patient had a highly unusual pres - entation of MPAL. She was diagnosed with XP at the age Germline predisposition is a contributing etiology of of 18 months with numerous lentigines on sun-exposed hematologic malignancies, especially in children and skin, when her family emigrated from Morocco to the young adults. Germline predisposition in myeloid neo - USA. The homozygous North African XPC founder muta - plasms was added to the World Health Organization tion was present. 10 She had her first skin cancer at the age 1 2016 classification, and current management recommen - of 8 years, and subsequently developed more than 40 cuta - dations emphasize the importance of screening appropri - neous basal and squamous cell carcinomas, one melanoma 2 ate patients. Rare syndromes of DNA repair defects can in situ , and one ocular surface squamous neoplasm. She 3 lead to myeloid and/or lymphoid neoplasms. Here, we was diagnosed with a multinodular goiter at the age of 9 describe our experience with hematologic neoplasms in years eight months, with several complex nodules leading the defective DNA repair syndrome, xeroderma pigmen - to removal of her thyroid gland. Histopathology showed tosum (XP), including myelodysplastic syndrome (MDS), multinodular adenomatous/papillary hyperplasia. At the secondary acute myeloid leukemia (AML), high-grade age of 19 years, she presented with night sweats, fatigue, lymphoma, and an extremely unusual presentation of and lymphadenopathy. Laboratory studies revealed pancy - mixed phenotype acute leukemia (MPAL) with B, T and topenia with hemoglobin 6.8 g/dL, platelet count myeloid blasts.
    [Show full text]
  • Hereditary Hearing Impairment with Cutaneous Abnormalities
    G C A T T A C G G C A T genes Review Hereditary Hearing Impairment with Cutaneous Abnormalities Tung-Lin Lee 1 , Pei-Hsuan Lin 2,3, Pei-Lung Chen 3,4,5,6 , Jin-Bon Hong 4,7,* and Chen-Chi Wu 2,3,5,8,* 1 Department of Medical Education, National Taiwan University Hospital, Taipei City 100, Taiwan; [email protected] 2 Department of Otolaryngology, National Taiwan University Hospital, Taipei 11556, Taiwan; [email protected] 3 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City 100, Taiwan; [email protected] 4 Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei City 100, Taiwan 5 Department of Medical Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan 6 Department of Internal Medicine, National Taiwan University Hospital, Taipei 10041, Taiwan 7 Department of Dermatology, National Taiwan University Hospital, Taipei City 100, Taiwan 8 Department of Medical Research, National Taiwan University Biomedical Park Hospital, Hsinchu City 300, Taiwan * Correspondence: [email protected] (J.-B.H.); [email protected] (C.-C.W.) Abstract: Syndromic hereditary hearing impairment (HHI) is a clinically and etiologically diverse condition that has a profound influence on affected individuals and their families. As cutaneous findings are more apparent than hearing-related symptoms to clinicians and, more importantly, to caregivers of affected infants and young individuals, establishing a correlation map of skin manifestations and their underlying genetic causes is key to early identification and diagnosis of syndromic HHI. In this article, we performed a comprehensive PubMed database search on syndromic HHI with cutaneous abnormalities, and reviewed a total of 260 relevant publications.
    [Show full text]
  • Pediatric Photosensitivity Disorders Dr
    FAST FACTS FOR BOARD REVIEW Series Editor: William W. Huang,MD,MPH W. Series Editor:William Swetha N.Pathak,MD;JacquelineDeLuca,MD Pediatric PhotosensitivityDisorders Table 1. Pediatric Photosensitivity Disorders Disease Pathophysiology Clinical Features Management/Prognosis Other/Pearls Actinic prurigo Strong association Pruritic crusted papules Phototesting: lesions Native Americans, (hydroa aestivale, with HLA-DR4 and nodules in both provoked by UVA or UVB; especially mestizos; Hutchinson (HLA-DRB1*0401/0407); sun-exposed and less spontaneous resolution hardening does not summer prurigo) may be a persistent frequently nonexposed may occur during late occur; histopathology: variant of PMLE sites (ie, buttocks); heal adolescence; may follow dermal perivascular (delayed-type with scarring; mucosal a chronic course that mononuclear cell hypersensitivity) and conjunctival persists in adulthood; infiltrate, lacks papillary from UVA or UVB involvement, with cheilitis photoprotection; topical dermal edema, can see often an initial or only corticosteroids and lymphoid follicles feature; worse in summer topical tacrolimus; from lip biopsies; but can extend to winter NB-UVB or PUVA; occurs hours to cyclosporine or days following azathioprine; thalidomide sun exposure (treatment of choice) for (vs solar urticaria) resistant disease noconflictofinterest. The authorsreport Long Beach,California. Center, LaserSkinCare DeLucaisfrom Dr. North Carolina. Winston-Salem, University, Forest Wake Pathakisfrom Dr. Bloom syndrome AR; BLM (encodes Malar telangiectatic
    [Show full text]
  • Treatment of Poikiloderma of Civatte with Ablative Fractional Laser Resurfacing: Prospective Study and Review of the Literature Emily P
    JUNE 2009 527 Vo l u m e 8 • Is s u e 6 CO P YR IGHT © 2009 ORIGINAL ARTICLES JOURN A L OF DRUGS IN DER MA TOLOGY Treatment of Poikiloderma of Civatte With Ablative Fractional Laser Resurfacing: Prospective Study and Review of the Literature emily P. Tierney MD and C. William Hanke MD MPH Laser and Skin Surgery Center of Indiana, Carmel, IN ABSTRACT Background: Previous laser treatments for Poikiloderma of Civatte (PC) (i.e., Pulsed dye, Intense Pulsed Light, KTP and Argon) are limited by side effect profiles and/or efficacy. Given the high degree of safety and efficacy of ablative fractional photothermolysis (AFP) for photoaging, we set out to assess the efficacy of PC with AFP. Design: A prospective pilot study for PC in 10 subjects with a series of 1−3 treatment sessions. Treatment sessions were adminis- tered at 6−8 week intervals with blinded physician photographic analysis of improvement at 2 months post-treatment. Evaluation was performed of five clinical indicators, erythema/telangiecatasia, dyschromia, skin texture, skin laxity and cosmetic outcome. Results: The number of treatments required for improvement of PC ranged from 1 to 3, with an average of 1.4. For erythema/te- langiecatasia, the mean score improved 65.0% (95% CI: 60.7%, 69.3%) dyschromia, 66.7% (95% CI: 61.8%, 71.6%), skin texture, 51.7% (95% CI: 48.3%, 55.1%) and skin laxity, 52.5% (95% CI: 49.6%, 55.4%). For cosmetic outcome, the mean score improved 66.7% (95% CI: 62.6%, 70.8%) at 2 months post treatment.
    [Show full text]