Journal of Medicine, Radiology, Pathology & Surgery (2017), 4, 22–27 NARRATIVE REVIEW Oral manifestation of genodermatoses L. Kavya, S. Vandana, Swetha Paulose, Vishwanath Rangdhol, W. John Baliah, T. Dhanraj Department of Oral Medicine and Radiology, Indira Gandhi Institute of Dental Sciences, Pudhucherry, India Keywords Abstract Genodermatoses, mutation, oral Genodermatoses are inherited dermatological disorders associated with the structure manifestation and functions of skin and its appendages. Several genodermatoses presenting with Correspondence multisystem involvement lead to increased morbidity and mortality. Dermatological Dr. L. Kavya, Department of Oral Medicine and diseases, besides including the skin and its supplements may also involve the oral cavity, Radiology, Indira Gandhi Institute of Dental which deserves special attention considering that they may be the only presenting sign Sciences, Pudhucherry, India. of these disorders. The important aspect to be noted about these disorders is the rarity Phone: +91-9442902745. of the conditions and lack of awareness among the population which are the major E-mail: [email protected] drawbacks in the early diagnosis and prompt management of these diseases. This review intends to outline various genodermatoses with their characteristic oral manifestations. Received: 11 April 2017; Accepted: 15 May 2017 doi: 10.15713/ins.jmrps.97 Introduction hence, it is simplified under three classifications based on its distinct features. Genodermatoses or genetic diseases are a group of inherited According to William et al. 2005:[3] skin disorders with a collection of cutaneous and systemic signs 1. Chromosomal and symptoms. In the oral cavity, a wide spectrum of diseases 2. Single gene occurs due to genetic modifications ranging from developmental 3. Polygenetic. disturbances of hard and soft tissues to precancerous and According to Irvine and Mellerio in 2010:[4] cancerous lesions. Dermatological diseases, besides including 1. Inherited immunobullous disorders the skin and its supplements may also involve the oral cavity, • Epidermolysis bullosa (EB) of different groups. which deserves special attention considering that they may be 2. Disorders of keratinization the early presenting clinical feature or the only sign of these • Ichthyosis disorders. The oral mucosal lesions in dermatological disorder • Palmoplantar keratoderma can be life-threatening and also affect the quality of life in terms • Erythrokeratoderma [1] of pain, discomfort, social, and functional limitations. • Follicular keratosis. The rarity of the conditions and lack of awareness are the 3. Hereditary disorders of pigmentation major complications in the management of these diseases. Several • Carney complex genodermatoses presenting with multisystem involvement may • Chediak-Higashi syndrome (CHS) [2] lead to increased morbidity and mortality. • Griscelli syndrome. 4. Familial multiple tumor syndrome Classification • Neurofibromatosis Type 1 and 2 • Tuberous sclerosis complex (TSC) Genodermatoses are a vast group of disorders including • Gardner syndrome common, uncommon, and very rare diseases. Categorizing • Cowden syndrome these diseases into different groups are arduous because of the • Peutz-Jeghers syndrome. overlapping clinical features of many conditions. It is difficult 5. Ectodermal dysplasias (EDAs) and disorders of to comprise all genodermatoses under one broad classification; ectodermal appendages 22 Journal of Medicine, Radiology, Pathology & Surgery ● Vol. 4:3 ● May-Jun 2017 Oral genodermatoses Kavya, et al. 6. Disorders with defects in DNA repair and chromosomal • Focal dermal hypoplasia syndrome instability • Multiple hamartoma syndrome (Cowden syndrome) • Bloom syndrome • Pachonychia congenita • Xerodermapigmentosum • EB • Cockayne syndrome. • Multiple endocrine neoplasia syndrome 7. Poikilodermatous disorders • White sponge nevus. • Rothmund-Thomson syndrome 4. Genodermatoses affecting jaw bones and facies • Dyskeratosis congenital (DKC) • Mccune-Albright syndrome • Acrokeratoticpoikiloderma of Weary • EDS • Kindler syndrome. • Marfan syndrome 8. Connective tissue disorders • Focal dermal hypoplasia syndrome • Ehlers-Danlos syndrome (EDS) • Gardner syndrome • Pseudoxanthoma elasticum • Basal cell nevus syndrome • Marfan syndrome • Orofacial digital syndrome Type 1. • Cutis laxa 5. Genodermatoses causing pigmentation of oral mucosa • Fabry disease • Carney complex • Williams syndrome • Neurofibromatosis Type 1 and 2 • Menkes kinky hair syndrome. • Mccune-Albright syndrome 9. Vascular and lymphatic disorders • Lipoid proteinosis • Osler-Rendu-Weber syndrome Type 1 and 2 • Pseudoxanthoma elasticum • Lymphedema distichiasis syndrome. • Peutz-Jeghers syndrome 10. Porphyrias • Congenital erythropoietic porphyria 11. Disorders associated with immunodeficiency • Hypomelanosis of ito • Wiskott-Aldrich syndrome • Sturge-Weber syndrome • Omenn syndrome. • Hereditary hemorrhagic telengiectasia syndrome. 12. Miscellaneous disorder 6. Genodermatoses with malignant potential • Bazex syndrome • Xeroderma pigmentosum (XP) • Goltz syndrome • DKC. • Pachydermoperiostosis In this review, the various genodermatoses along with • Nail-patella syndrome their oral manifestations are discussed. [Table 1] shows Oral • Apert syndrome. genodermatoses with their corresponding mutated genes. Arora and Mane proposed a classification in 2016:[5] 1. Genodermatoses affecting teeth and dentition EB • Ichthyosis • Sjogren-Larrson syndrome EB is a chronic blistering disease of the skin and mucosa. • Incontinentia pigment The three major types of EB are EB simplex, junctional EB, • EDS and dystrophic EB. Oral involvement has been reported in • Focal dermal hypoplasia syndrome the junctional and dystrophic forms of the disease, which is characterized by bulla and vesicle formation following mild • Gardner syndrome [6] • EDA physical trauma. Oral manifestations include blistering • Hyperimmunoglobulin E syndrome (Job syndrome). and ulceration of the oral mucosa, abnormal tooth eruption, 2. Genodermatoses affecting periodontium and gingiva depapillation of tongue, ankyloglossia, ablated palatal rugae, • Ichthyosis and microstomia. • Sjogren-Larrson syndrome Ichthyoses • Papillon Lefevre syndrome • Tuberous sclerosis Ichthyoses form a large, clinically and etiologically heterogeneous • CHS group of cornification disorders that typically affect all or most of • EDS the skin surface.[7] It is caused by abnormality in keratinization • Focal dermal hypoplasia syndrome. and exfoliation of the horny cell layer. Oral and dental findings 3. Genodermatoses affecting oral mucosa reported in ichthyosis include gingivitis, periodontitis, • Darier’s disease enamel hypoplasia, high caries incidence, delayed primary • Neurofibromatosis Type 1 and 2 and permanent teeth eruption, bruxism, bifid teeth, irregular • CHS morphology of teeth, and hyperkeratotic plaques on the tongue. • EDS Angular cheilitis and facial dermatitis may occur as side effects of • Lipoid proteinosis oral retinoid therapy. Journal of Medicine, Radiology, Pathology & Surgery ● Vol. 4:3 ● May-Jun 2017 23 Kavya, et al. Oral genodermatoses Palmoplantar keratoderma (PPK) Table 1: Oral genodermatoses with their corresponding mutated genes PPK is a common hereditary cutaneous disorder characterized Oral genodermatoses Mutated gene by marked hyperkeratosis on the surface of palms and soles.[8] EB KRT5/KRT14/COL7A1 Periodontitis can affect both the deciduous and permanent teeth. Initially, there tends to be gingival inflammation, which can be Ichthyoses ABCA12/FLJ39501/FLG/STS followed by destruction of periodontium leads to premature loss PPK KRT1/KRT16/TRPV3 of primary teeth. CHS CHS1 gene in 1q42‑43 band NF NF1 and NF2 CHS TSC TSC1 (9q34), TSC2 (16p13.3) CHS is an autosomal recessive disease that affects the production of organelles in many cells including melanocytes, platelets, and Gardner syndrome APC (5q21q22) leukocytes. Neutrophils are characterized by abnormal giant Peutz‑Jeghers syndrome STK11 lysosomes containing enzymes and with impaired ability to DKC NOP10/NHP2 [9] release them. It is associated with severe gingivitis, periodontal EDS COL5A1 disease and premature loss of dentition. Marfen syndrome FBN1 Neurofibromatosis Cowden’s syndrome PTEN (10q22‑23) Neurofibromatosis comprises several distinct genetic disorders Apert syndrome C934G/C937G that lead to the formation of tumors surrounding nerves and many EB: Epidermolysis bullosa, PPK: Palmoplantar keratoderma, other pathological features. Oral lesions are present in 5-10% of CHS: Chédiak‑Higashi syndrome, TSC: Tuberous sclerosis complex, NF: Neurofibromatosis, EDS: Ehlers‑Danlos syndrome, DKS: Dyskeratosis cases, as papillomatous tumors of palate, buccal mucosa, tongue congenital and lips, or as macroglossia, which is usually asymmetrical.[10] Common sites of the oral solitary neurofibromas include tongue, buccal mucosa, alveolar ridge, labial mucosa, palate, gingiva, lesions are usually flat, painless, brown pigmented patches of nasopharynx, paranasal sinuses, larynx, floor of the mouth, and the buccal mucosa, tongue or labial mucosa. Microscopically, salivary gland. Tumors may also arise within the bone. these lesions show mild acanthosis with elongation of rete pegs and increased production of melanin pigment in the basal layer [14] TSC without increase in the melanocyte number. TSC is an autosomal dominant, systemic disorder characterized EDA by the formation of hamartomas in multiple organ systems, most commonly