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Genodermatoses Dental Science - Review Article Genodermatoses N. Aravindha Babu, E. Rajesh, Jayasri Krupaa, G. Gnananandar Department of ABSTRACT Oral pathology and Microbiology, Sree Genodermatoses are an inherited disorder, present with multisystem involvement. Help us to identify regular Balaji Dental College mutations and appalling skin diseases with recessive inheritance. Genetic heterogeneity is very common, and and Hospital, Bharath molecular diagnosis requires a broad effort. Recurrent mutations in unrelated families were seen in families University, Chennai, with xeroderma, Griscelli. It seems likely that eventually oligonucleotide arrays will replace most other methods Tamil Nadu, India for routine mutation scanning of the more common diseases and planned sequencing will be increasingly used for rarer diseases. Address for correspondence: Dr. G. Gnananandar, E-mail: gnanam.anu.rg@ gmail.com KEY WORDS: Benign, dyskeratosis congenital, ectodermal dysplasia, Ehlers–Danlos syndrome, epidermolysis Received : 31-10-14 bullosa, hereditary, hidrotic ectodermal dysplasia, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, Review completed : 31-10-14 intraepithelial-dyskeratosis, keratosis follicularis, multiple hamartoma syndrome, pachyonychia congenital, Accepted : 09-11-14 Peutz–Jeghers syndrome, tuberous sclerosis, Warty dyskeratoma, white sponge nevus, xeroderma pigmentosum enodermatoses consign to an inherited skin disorder associated Classification G with structure and function. Several genodermatoses present with multisystem involvement lead to increased morbidity and • Chromosomal mortality. Genetic research Center resolute on identifying the • Single gene molecular basis of such outrageous skin diseases with recessive • Polygenetic.[2] inheritance. This would help us identify regular mutations, founder effects etc., which would reduce the cost of selection Ectodermal Dysplasia patients and their carrier parents. During the years 2011–2013, 100 patients were referred to the center with Genodermatoses. Group of inherited condition. Two or more ectodermally The commonest group was ichthyosis, followed by epidermolysis derived anatomical structures fail to develop. Inherited one bullosa, ectodermal dysplasia, albinism, cutis laxa, progeroid of genetic pattern, autosomal dominant, autosomal recessive, conditions, precancerous conditions xeroderma pigmentosum, X‑linked. Rothmund Thomson syndrome, dyskeratosis congenita. Genetic heterogeneity is very common, and molecular diagnosis requires Hypohidrotic ectodermal dysplasia an extensive effort. Recurrent mutations in unrelated families were seen in families with xeroderma, griscelli. Prenatal diagnosis X‑linked ‑ mapped in the proximal area of the long arm of could be provided for ichthyosis, infantile hyalinosis, and progeria. band Xq‑12‑q13.1 Decreased expression of the epidermal growth factor receptor. Gene ED1 is responsible. Autosomal This is the largest cohort of mutation proven patients with recessive ‑ phenotypically indistinguishable from the X‑linked genodermatoses from India.[1] form. Gene is located at dl (downless) locus.[3,4] Access this article online Quick Response Code: Hidrotic ectodermal dysplasia Website: www.jpbsonline.org GJB6 is the causative gene. This encodes for connexin 30. Located at pericentromeric region of chromosome 13q. For DOI: patients with cleft lip/palate‑mutation PVRL 1, encoding a 10.4103/0975-7406.155903 cell to cell adhesion molecule/herpes virus receptor. Reduction in number of, sweat gland, hair follicle, and sebaceous gland. How to cite this article: Babu NA, Rajesh E, Krupaa J, Gnananandar G. Genodermatoses. J Pharm Bioall Sci 2015;7:S203-6. Journal of Pharmacy and Bioallied Sciences April 2015 Vol 7 Supplement 1 S203 Babu, et al.: Genodermatoses Salivary glands may show ectasia of ducts and inflammatory Xeroderma pigmentosum changes.[5] Inherited as an autosomal recessive trait. Caused by one of the White sponge nevus several defects in the excision repair and/or postreplication repair mechanism of DNA. Inability of the epithelial cells to repair Defect in normal keratinization of the oral mucosa. Mutation in ultraviolet (UV) light‑induced damage. Markedly increased kerarin‑4 or keratin‑13. Inherited as autosomal dominant trait. tendency to sunburn. Atrophy, freckled pigmentation, and High degree of penetrance and variable expressivity.[6] patchy depigmentation, soon follow. In early childhood, actinic keratoses begin developing. These lesions quickly progress to Hereditary, benign, intraepithelial‑dyskeratosis squamous cell carcinoma. Triracial isolate (native American, black and white). Autosomal Basal cell carcinoma, melanoma and nonmelanoma skin cancer dominant transmission. A segment of DNA localized at 4q35 also develops occur before 20 years of age. Development of is duplicated resulting in triple alleles for 2 linked markers squamous cell carcinoma of the lower lip and the tip of the suggesting that gene duplication is responsible for the disorder tongue Nonspecific Cutaneous premalignant lesions and develop during childhood. The oral lesions are similar to those malignancies that occur are microscopically indistinguishable of white sponge nevus. Milder cases may exhibit the opalescent from those observed in unaffected patients.[11] appearance of leukoedema. Superimposed candidal infection. Develop during childhood. The oral lesions are similar to Incontinentia pigmenti those of white sponge nevus. Milder cases may exhibit the opalescent appearance of leukoedema. Superimposed candidal Inherited as an X‑linked dominant trait. Single unpaired gene infection.[7] on the X‑chromosome being lethal for most males. Affected patients show chromosomal instability. Primarily affecting the Pachyonychia congenita skin, eyes and central nervous system (CNS), as well as oral structures. Begin in the first few weeks of infancy vesicular Inherited as an autosomal dominant trait. Specific stage ‑ vesiculobullous lesions appear on the skin of the trunk mutations in the keratin 16 gene‑Jadassohn–Lewandowsky and limbs. Spontaneous resolution occurs within 4 months. type. Mutations of the keratin 17 gene are associated with Verrucous stage ‑ verrucous cutaneous plaques develop, the Jackson–Lawler form. The oral lesions are seen in the affecting the limbs. These clear by 6 months of age. Hyper Jadassohn–Lawandowsky form. Whitish plaques on the pigmentation stage ‑ macular, brown skin lesions appear, mucosa of the cheeks, tongue. Marked hyperpa rakeratosts characterized by a strange swirling pattern. Atrophy and and acanthosis with perinuclear clearing of the epithelial depigmentation stage ‑ atrophy and depigmentation of the cells. The free margins of the nails are lifted up because of skin ultimately occur. an accumulation of keratinaceous material in the nail beds. Marked hyperkeratosis of the palmar and plantar surfaces, Central nervous system abnormalities mental retardation, producing thick, callouslike lesions. The rest of the skin shows seizure disorders, motor difficulties, strabismus, cataracts, punctate papules, representing an abnormal accumulation of retinal vascular abnormalities, optic nerve atrophy keratin in the hair follicles. Formation of painful blisters on oligodontia (hypodontia), delayed eruption, hypoplasia of the the soles of the feet after a few minutes of walking during teeth. The teeth are small and cone‑shaped, both the primary warm weather. Marked hyperpa rakeratosts and acanthosis and permanent dentitions are affected. Histopathology; with perinuclear clearing of the epithelial cells.[8,9] vesicular stage ‑ intraepithelial clefts filled with eosinophils are observed. Verrucous stage ‑ hyperkeratosis, acanthosis, and Dyskeratosis congenita papillomatosis are noted. Hyperpigmentation stage ‑ shows numerous melanin‑containing macrophages (melanin Inherited as an X‑linked recessive trait. Striking male incontinence) in the subepithelial connective tissue.[12] predilection. Autosomal dominant and autosomal recessive forms are less common. Mutations in the DKC1 gene. The Keratosis follicularis mutated gene appears to disrupt the normal maintenance of telomerase. Skin hyper pigmentation develops, affecting the Autosomal dominant, a high degree of penetrance and variable face, neck, and upper chest. Dysplastic changes of the nails expressivity. Mutation of the gene that encodes an intracellular intraorally, the tongue and buccal mucosa develop bullae; these calcium pump (ATP2A2 located at 12th chromosome). are followed by erosions and eventually leukoplakic lesions. Suprabasal clefting and several “corps ronds” clinical features The leukoplakic lesions are considered to be premalignant. common in childhood, numerous erythematous, often pruritic, Thrombocytopenia is usually the first hematologic problem papules on the skin, common on scalp and trunk, accumulation that develops. Followed by anemia. Ultimately aplastic anemia of keratin, produce rough texture. Foul odor is due to bacterial develops. Hyperorthokeratosis with epithelial atrophy. As degradation of keratin, Palm and sole exhibits pits and keratosis. the lesions progress, epithelial dysplasia develops until frank Nails show longitudinal lines, ridges or painful splits. Become squamous cell carcinoma evolves.[10] worse during the summer either due to the sensitivity to UV S204 Journal of Pharmacy and Bioallied Sciences April 2015 Vol 7 Supplement 1 Babu, et al.: Genodermatoses light or increased sweating that causes more epithelial clefting, Oral manifestations
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