Review Article http://doi.org/10.18231/j.jeths.2019.

016

Oral genodermatoses
Akshat Sachdeva1, Sumit Bhateja2*, Geetika Arora3
1Dental Surgeon, 2,3Reader, 2Dept. of Oral Medicine & Radiology, 3Dept. of Public Health Dentistry, 1,2Manav Rachna Dental College,
Faridabad, Haryana, Inderprastha Dental College, Ghaziabad, Uttar Pradesh, India

*Corresponding Author: Akshat Sachdeva

Email: bhateja.sumit@gmail.com

Abstract
Genodermatoses alludes to a set of inherited dermatologic disorders. A significant variety of these disorders is unusual and present with
oral indications called oral genodermatoses. They typically present with multisystem association prompting an expanded tempo of
morbidity and mortality. The oral findings maybe perhaps distinct and may offer the primary clue of underlying genetic disorder. The
present article discusses various genodermatomes presenting with oral manifestations and an approach to the diagnosis of these disorders.

Keywords: Genodermatoses, Dermatologic features, Oral manifestations, Genetics.

Introduction a. McCune-Albright syndrome.

Genodermatoses refers to a bunch of inherited disorders b. Marfan syndrome.
with skin manifestations. Several of these disorders have a c. Gardner syndrome.
rare incidence. Few present with certain oral manifestations d. Basal cell nevus syndrome.
as well and are hence referred to as oral genodermatoses.1 5. Genodermatoses causing pigmentation of oral mucosa:
These disorders might vary from developmental a. Neurofibromatosis type 1 and 2.
disturbances of hard and soft tissues to precancerous and b. Peutz-Jeghers syndrome.
cancerous lesions.2 Rarity of these conditions can lead to c. Hereditary hemorrhagic telangiectasia syndrome.
complications in the diagnosis and management of these 6. Genodermatoses with malignant potential:
disorders. a. Xeroderma pigmentosum.
Since the past few years, there has been a sudden b. Dyskeratosis congenita.
explosion with regard to numerous innovations within the
field of molecular biology which has appreciably According to Irvine and Mellerio, oral genodermatoses can
transformed our current day expertise of pathogenesis of be classified as:4
many human diseases. 1. Inherited immunobullous disorders:
a. Epidermolysis bullosa of different groups.
Classification 2. Disorders of keratinization:
There have been several proposed classifications of oral a. Icthyosis.
genodermatoses by various authors. Arora M et al (2016) b. Follicular keratosis.
classified oral manifestations of genodermatoses into six c. Palmoplantar keratoedema.
different groups as:3 3. Hereditary disorders of pigmentation:
1. Genodermatoses affecting teeth and dentition: a. Carney complex.
a. Icthyosis. b. Chediak-Higashi syndrome.
b. Sjogren-Larrson syndrome. 4. Familial multiple tumor syndrome:
c. Incontinenia pigmenti. a. Neurofibromatosis type 1 and 2.
d. Ehlers Danlos syndrome. b. Tuberous sclerosis complex.
e. Focal dermal hypoplasia syndrome. c. Gardner syndrome.
f. Gardner syndrome. d. Cowden syndrome.
g. Ectodermal dysplasia. e. Peutz–Jeghers syndrome.
2. Genodermatoses affecting periodontium and gingiva 5. Ectodermal dysplasia and disorders of ectodermal
a. Icthyosis. appendages.
b. Papillon Lefevre syndrome. 6. Disorders with defects in DNA repair and chromosomal
c. Tuberous sclerosis. instability:
d. Chediak-Higashi syndrome. a. Bloom syndrome.
3. Genodermatoses affecting oral mucosa: b. Xerodermapigmentosum.
a. Darier’s disease. 7. Poikilodermatous diorders:
b. Neurofibromatosis type 1 and 2. a. Rothmund Thomson syndrome.
c. Multiple hamartoma syndrome. b. Dyskeratosis congenital.
d. Epidermolysis bullosa. c. Kindler syndrome.
e. Pachonychia congenital. 8. Connective tissue disorders:
4. Genodermatoses affecting jaw bones and facies: a. Ehlers-Danlos syndrome.
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Akshat Sachdeva et al. Oral genodermatoses

b. Marfan syndrome. Marfan’s Syndrome

c. Pseudoxanthoma elasticum. Marfan's disorder is a hereditary condition of the connective
tissue and has appeared to display visual, skeletal and
9. Vascular and lymphatic disorders: cardiovascular signs. People influenced with the disorder
a. Osler-Rendu-Weber syndrome type 1 and 2. will in general be abnormally tall with lengthy appendages.
10. Porphyrias. Spine curves on one side called scoliois.1 Severe
11. Disorders associated with immunodeficiency: complications like aortic aneurysms and left ventricular
a. Wiskott-Aldrich syndrome. dysfunction have likewise been seen. Syndrome is carried
12. Miscellaneous disorders: by the gene FBN1 that encodes fibrillin-1 inherited as a
a. Goltz syndrome. dominant trait.13
b. Nail-patella syndrome. Oral Manifestations: Jaw bones present with
c. Apert syndrome. retrognathia, crowding of teeth. Root distortion and irregular
There are many genetic disorders affecting the mouth and pulp shapes have been every now and again watched.12
adjoining areas. Few of them along with their oral
manifestations have been discussed: Gardner’s Syndrome
It is an uncommon autosomal dominant disorder portrayed
Epidermolysis Bullosa by intestinal polyposis, sebaceous cysts and jaw osteomas. It
Epidermolysis bullosa refers to a group of heritable genetic has been related to X gene located in chromosome 5q21.14
diseases having three major varieties particularly simple, The condition is also associated with epidermoid cysts, eye
junctional and dystrophic.5 It is characterized by blister abnormalities and malignancies like thyroid carcinomas and
formation and scarring. Flat, pink bullae on ankles, knees, adenocarcinomas. The condition is usually asymptomatic.
hands, elbow and feet are visible. Maximum instances are Oral Manifestations: Multiple supernumerary peg
associated with anchoring filaments and anchoring fibrils shaped and unerupted teeth are present in the incisor, cuspid
which gives rise to an interconnecting network. In addition, and bicuspid region. Compound odontomas are usually seen
mutations of gene coding for type VII collagen of anchoring in the same manner as supernumerary teeth. Osteomas can
fibrils have likewise been distinguished.6 also be felt through the skin and oral mucosa.15
Oral Manifestations: Oral involvement has been
observed in junctional and dystrophic forms of the disease. Cowden Syndrome
Few sufferers have shown to evince oral bullae and milia Also known as “multiple hamartoma syndrome”. It is an
formation.7 autosomal dominant disorder having multiple tumor-like
growths called hamartomas. They are characterized by
Peutz-Jeghers Syndrome mucocutaneous papules involving oral, nasal and intestinal
It is an autosomal dominant ailment characterized by mucosa.16 Patients suffering from Cowden’s syndrome are
formation of gastrointestinal polyps and maculae.8 Mutation also prone to developing cancers including breast, thyroid
of the gene LKB1/STK11 (serine/threonine-protein kinase and uterus. Mutation in the PTEN gene is the causative
11) is accountable for its causation.9 The condition typically factor for the syndrome discovered in majority of patients.17
includes the periorofacial areas (mouth, nose). Oral Manifestations: Oral findings include presence of
Gastrointestinal adenocarcinoma may develop in 2-3% of hamartomas on gingiva, buccal and palatal mucosa.
affected individuals. Patients stricken by this disorder have a Appearance of multiple mucosal papules has been described
nearly 50% threat of passing on the mutation to each of their as cobblestone-like seen in about 40% of patients.18.
progeny.10
Oral Manifestations: Pigmented lesions on the skin Neurofibromatosis
around lips and vermilion zone are commonly seen. Brown Neurofibromatosis is inherited as an autosomal dominant
pigmented macules are usually present during childbirth or trait. It is a neurocutaneous disorder ordered into two sorts:
noted in early adolescence.11 Lesions are viewed as painless neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2).19
patches on buccal or labial mucosa and tongue. NF1 is also called as von Recklinghausen disease. It is
characterized by presence of numerous café-au-lait spots
Ehlers-Danlos Syndrome more noteworthy than 0.5 cm in diameter. NF1 affects 1 in
It refers to a collection of inherited connective tissue 3500 individuals worldwide and is caused by mutation on
disorders. The condition occurs as a result of an chromosome 17q11.2. NF2 is commonly known as bilateral
imperfection in collagen amalgamation. It mostly influences acoustic neurofibromatosis. Identifying features of NF2
joints, skin and vessels. Nearly half of the affected include bilateral schwannomas involving eighth cranial
individuals have a mutation in COL5A1 or COL5A2.1 nerve and lesions on brain and spinal cord.19 NF2 is caused
Oral Manifestations: Extra-oral signs consist of slender due to mutation on chromosome 22q12.2.
and uneven face, scars on the skin and forehead and Oral Manifestations: Oral soft tissue neurofibromas are
repeated incidence of TMJ dislocation. Intra-oral located in the soft tissues such as cheek, tongue, floor of
manifestations comprise of high arched palate, crowding of mouth and lips with tongue being the most commonly
teeth and fragile mucosa seen with bruising.12 affected part.20 Superficial lesions give the tongue a scrotal
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Akshat Sachdeva et al. Oral genodermatoses

or fissured appearance, while deep seated tumors give Cutaneous findings inconsistent with the patient’s age, such
appearance of macroglossia. as loose, hanging skin in a newborn or cutaneous
malignancy in a child are strongly suggestive of a genetic
Dyskeratosis Congenita skin disorder. Clinical presentation of many genodermatoses
The disorder is an X-linked recessive one and is changes with the patient’s age and some genetic disorders
characterized by a classical triad of nail dystrophy, lacy manifest only in adolescence or adulthood.
cutaneous pigmentations and oral leukoplakia. Affected
individuals have a high tendency for malignancies and Obtain thorough medical history
subsequent bone marrow failure. Malignancy often develops Family history has often been called “the first genetic test”26
in the third decade of life.21 Bone marrow failure can lead to the physician should examine first- and second-degree
thrombocytopenia, anemia and ophthalmic abnormalities. relatives, or obtain clinical pictures and medical documents,
Significantly shortened lifespan has been seen in individuals in order to be able to recognize subtle phenotypic features.
affected with more serious form of the disorder.22 The The country of origin, and in particular ethnicity, may affect
condition occurs as a result of one or more mutations in the the molecular and clinical presentation of some genetic
long arm of the X chromosome in gene DKC1. pigmented disorders. For e.g.: positive family history in a
Oral Manifestations: Leukoplakia involving lingual & young adult with blisters and erosions in the large folds
buccal mucosa and palate has been observed in majority of points to the diagnosis of Hailey-Hailey disease. Many
affected patients. The lesion may progressively become genodermatoses occur sporadically as a result of new
verrucous and ulcerated. An increased incidence of mutations.25
periodontal disease and dental caries has also been
observed.22 Perform complete physical examination
Identification of skin changes and appendages are helpful in
Hemorrhagic Telangiectasia narrowing the differential diagnosis and sometimes even in
It is also known as Osler-Weber-Rendu syndrome. It is a determining the final diagnosis. Congenital anomalies and
rare autosomal dominant disorder leading to abnormal extracutaneous findings may point to a specific diagnosis.
vessel formation affecting the skin and mucous membranes. Early diagnosis of a genetic disorder may prompt adequate
Certain arteriovenous malformations become more clinical follow-up and early treatment of systemic
prominent with advancing age. Two genetic types have been manifestations.
observed: HHT-1 and HHT-2.
Oral Manifestations: Oral lesions maybe nodular and Laboratory testing
can be seen on buccal mucosa, tongue, lips and gingiva.23 Skin biopsies should be obtained for histopathology,
Shading may fluctuate from brilliant red to purple. including special stains and immunochemistry, electron
microscopy, and/or cell cultures. Histopathology is crucial
MEN’s Syndrome in determining the morphology of cutaneous features, and
Multiple endocrine neoplasia (MEN) syndrome is an frequently facilitates establishing the correct diagnosis.
uncommon autosomal prevailing issue related with Biochemical and enzymatic tests are important tools in the
neoplasm of endocrine gland. Two main types have been diagnostic workup of metabolic diseases and primary
identified: MEN-I and MEN-II. MEN-I is portrayed by nutritional disorders associated with cutaneous symptoms.
tumor of pituitary organ and pancreas. MEN-II is portrayed
by various pheochromocytomas and thyroid carcinomas. Nails as Diagnostic Clue
MEN is associated with oncogenic point mutations of RET Appendageal structures like nails can act as good reflectors
proto-oncogene on chromosome locus 10q11.2.1 for presence of many systemic disorders. Nails may be the
Oral Manifestations: Oral lesions present as nodular or affected primary site in some genodermatoses. Nail
diffuse swellings in the oral cavity. This feature is involvement maybe categorized into three groups:27
pathognomonic and hence also called as “multiple mucosal 1. Genodermatoses with characteristic nail changes: Few
neuroma syndrome”. This oral manifestation is often the genodermatoses present with trademark nail changes.
first clue to the syndrome at an early age.24 When experienced with such nail changes, these
clutters merit the principal demonstrative thought.
Diagnosis of Genodermatoses Examples include: pachonychia congenital, nail-patella
It is rightly quoted as “the skin frequently mirrors systemic syndrome, yellow nail syndrome, Darier’s disease and
genetic diseases”. Genodermatoses are rare skin conditions porphyrias.
for which a multistep approach is required to diagnose 2. Genodermatoses with significant nail involvement: A
them.25 few genodermatoses have nail changes sufficiently
noteworthy to stand out for clinician during first visit,
Recognize “Red Flags” however not normal for these clutters. Examples
Cutaneous findings can represent significant clues for include: epidermolysis bullosa, dyskeratosis congenital,
identifying a syndrome. Persistent erythroedema at birth Kindler syndrome and incontinentia pigmenti.
might be associated with hereditary disorders like icthyosis.
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Akshat Sachdeva et al. Oral genodermatoses

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