about various genodermatoses and classified according to clinical presentation. mentioned are introduction clinical features histology management of each disease.

1. GENODERMATOSES
Moderator-Dr. Amit Tiwari Sir
Presentor-Dr. Mehul Choudhary

2. INTRODUCTION
 Genodermatoses represents hereditary skin
diseases, many of which are also accompanied by
various systemic manifestations.
 Some are characterized particularly by alterations in
the normal keratinization process.
 These have been specifically referred to as
Genokeratoses.
 There is no universally accepted classification of
these dermatologic disorders.

3. DISORDERS OF KERATINIZATION

4. ICHTHYOSES
 The primary ichthyoses are a heterogeneous group of
inherited disorders featuring excessive scale.
 Disorder of keratinization associated with decrease
conversion of profilaggrin to filaggrin.
 Fillagrin is an epidermal protein which is needed for
aggregation of keratin intermediate filament and retention
of moisture in stratum corneum.
 It characterized by fine scaling predominantly with
sparing of the flexures and tendency towards
improvement in summer months.

5. TYPES OF ICHTHYOSES

6. Clinical features:-
 Xerosis
 Scales usually more prominent on the extensor
surface of extremities with flexure sparing.
 Hyperlinear palms/palmo-plantar thickening.
 Ichthyosis vulgaris is frequently assosiated with
atopic dermatitis and keratosis pilaris.

8. Treatment
 Maintain hydration- Emollients (Vaseline, Liquid
Paraffin, Glycerin).
 Topical Urea (10-30%) acts as hemctants.
 Salicylic Acid and Lactic acid- as Keratolytics
 Topical calcipotriene.
 Avoidance of Strong Soap.

9. Darier Disease
 Keratosis Follicularis, Dyskeratosis Follicularis, Darrier-
White Disease.
 Uncommon genodermatoses, Autosomal Dominant
 Mutation in ATP2A2 gene.
 Lack of cohesion among the surface epithelial cell
characterizes this disease.
 Mutation of a gene that encodes intracellular calcium
pump- cause for abnormal desmosomal organization in
the affected epithelial cells.

10. Clinical Features
 Persistent, greasy, scaly papules which tend to occur
over the seborrhoeic areas of the face, forehead, ears,
nose, neck, chest and back.
 The papules are firm, harsh and feel like coarse
sandpaper.
 Several small papules grow together and may form warty
lesions which cam become quite smelly within skin folds.
 Small pits (tiny indentation) on the palms and soles may
occur and are very characteristic of Darrier disease.
 V-shaped notch at the free edge of the nail is
pathognomic.

14. HISTOPATHOLOGY
 The suprabasal cleft of the
epidermis contains
acantholitic cells (indicated
by arrowheads), associated
with hyperkeratosis
(indicated by white arrow
heads) and rounded
dyskeratotic cells (indicated
by yellow arrows).

15. Treatment And Prognosis
 The condition is not premalignant or otherwise life
threatening, genetic counseling is appropriate.
 Photosensitive patients should use sunscreen, and
all patients should minimize unnecessary exposure
to hot environments.
 For relatively mild cases, keratolytic agents may be
the only treatment required.
 For more severely affected patients, systemic
retinoids are often beneficial.

16. PALMOPLANTAR KERATODERMAS
 Also known as Keratosis Palmaris et Plantaris.
 Its inherited or acquired heterogenous group of skin
condition with chronic thick hyperkeratotic palms/soles.
 Transgradient- Hyperkeratosis that crosses palm/soles
edge contiguosly or as callosities on pressure points on
the fingers or knuckles, or elsewhere
 Non-Transgradient- Hyperkeratosis involves only the
palms and soles.
 The condition runs in families, its AD or AR usually more
severe (i.e. mal de meleda, papillon-lefevre).

17.  PPK is classified clinically as
 Diffuse type - Uniform involvement of the
palmoplantar surface.
 Focal type – Localized areas of hyperkeratosis
located mainly on pressure points and sites of
recurrent friction.
 Punctate Type – Multiple small, hyperkeratotic
papules, spicules, or nodules on the palms and soles
may involve the entire palmoplantar surface.

22.  The genetic basis of many keratodermas particularly
invoves mutation in genes encoding-
1. Keratins
2. Connexins
3. Desmosomal components

23. HISTOPATHOLOGY
 Histologic features of
nonepidermolytic PPK.
Note the massive
hyperkeratosis,
acanthosis and
hypergranulosis.

24. TREATMENT
 General measures include evaluation of family members and genetic
counseling.
 Regular foot care, careful selection of footwear, and treatment of
fungal infections are important
 Topical agents include-
1. Keratolytivs-eg 5-10% salicylic acid
2. Emollients
3. Benzoic acid compounds
4. Topical retinoids- eg tretinoin
5. Topical Steroids
 Systemic Agents includes Retinoids
 Dermabrasion,CO2 Laser, Surgical excision For sever, difficult to
treat keratoderma.

25. GENETIC BLISTERING DISORDER

26. EPIDERMOLYSIS BULLOSA
 A heterogeneous group of inherited blistering
mucocutaneous disorders.
 A specific defect in the attachment mechanisms of
the epithelial cells, either to each other or to the
underlying mechanism.
 Depending on the defective mechanism of cellular
cohesion, there are four broad categories:
1. EB Simplex- Keratin 5,14
2. EB Junctional- a3,b3
3. EB Dystrophic- type VIII collagen

27. Clinical Features
 Initial lesions are vesicles or bullae.
 Seen early in life and develop on areas exposed to low grade, chronic trauma,
such as the knuckles or knees.
 The bullae rupture resulting in erosions or ulceration that ultimately heal with
scarring except in EB simplex.
 Appendages such as fingernails may be lost.
 Dystrophic epidermolysis bullosa represents one of the more debilitating forms of
the disease.
 Vesicles and bullae forms with even minor trauma
 Hand Function is often greatly diminished resulting in fusion of fingers into mitten
like deformity.

28. Mitten like deformity

29. HISTOPATHOLOGY
 Features may vary with the
type being examined.
 Simplex shows intraepithelial
clefting by light microscopy.
 Junctional and dystrophic
forms shows subepithelial
clefting.
 Electron microscopy reveals
clefting at the level of the
lamina lucida of the BMZ in
juntional form.
 Below the lamina densa of
BMZ in dystrophic form.

30. MANAGEMENT AND TREATMENT
 Blistering becomes less frequent as age advances.
 Prevention of trauma.
 Prevention of infection.
 Avoidance of provocative factors.
 Treatment of complications.
 Genetic counseling.
 Water or air mattress to reduce friction.
 Adhesives are avoided, instead use paraffin
impregnates gauze for dressings.

31. DISORDERS OF CONNECTIVE TISSUE

32. Pseudoxanthoma Elasticum
 This is a disorder of elastic tissue most obviously in
the skin, blood vessels and eyes.
 Either autosomal dominant or recessive.
Pathology-
 The elastic fibres in the mid-dermis becomes swollen
and fragmented; their calcification is probably a
secondary feature.
 The elastic tissue of blood vessels and of retina may
also be affected.

33. Clinical Features
 The skin of neck and axillae, and occasionally of other
body folds, is loose and wrinkled.
 Groups of small yellow papules give these areas a
‘plucked chicken’ appearance
 Breaks in retina show as angioid streaks.
 Arterial involvement may lead to peripheral, coronal or
cerebral arterial insufficiency.
 Complications include hypertention, recurrent gut
haemorrhages, ishemic heart disease, cerebral
haemorrhage.

35. Histopalthology
 Affected elastic fibers
are basophilic and
irregular, appearing as
widely dispersed
granular material
amidst normal collagen
fibers.
 Increased dermal
mucin may be evident
 There is no effective treatment.

36. Ehlers-Danlos Syndrome
 A group of heterogenous inherited connective tissue
disorders
 Caused by the abnormality in the formation or
modification of collagen and the extracellular matrix.
 Inherited as an autosomal dominant or recessive
trait.
 Defects of type 1,3,5 collagen

37. Classification Of EDS
 Six subtypes
1. Classical
2. Vascular
3. Hypermobility
4. Kyphoscoliotic
5. Arthrochalasia
6. Drematosparaxis

38. Clinical Features
 Hyperelasticity of skin.
 Hyperextensibility of the joints.
 Fragility of skin and blood vessels.
 Vascular type of ehlers-danlos (ecchymotic type)-
extensive bruising that occurs with everyday trauma.
 Unusual healing response occur with relatively minor
injury to the skin termed “papyraceous scarring”
(resembles crumpled cigarette paper).

42. Histopathology And Management
 Light microscopy revealed skin of normal thickness with
loosely arranged collagen fibers and rare organized
bundles.
 Elastic tissue was present and disorganized.

43. EDS MANAGMENT
 Patient education
 Prevention and early recognition of
injuries/complications.
 Monitoring & interventions
 Particular manifestation
 Complications with each forms EDS
 Medical alert device
 No Medical treatments.

44. ECTODERMAL DYSPLASIA

45.  A group inherited conditions in which two or more
ectodermally derived anatomic structures fail to
develop.
 Classified based on clinical features
1. Hypohydrotic ED-X linked recessive
2. Hydrotic ED-autosomal dominant
 The various types of this disorder may be inherited in
anyone of several genetic patterns.

46. Hypohidrotic ectodermal dysplasia
 X-linked – mapped in the proximal area of the long
arm of band Xq-12q13.1
 Decreased expression of the epidermal growth factor
receptor. Gene ED1 is responsible.
 Autosomal recessive- phenotypically
indistinguishable from the X linked form.
 Gene is located at downless locus

47. Hidrotic ectodermal dysplasia
 GJB6 is the causative gene.
 This encodes for connexin 30
 Located at pericentromic region of chromosome 13q.
 For patient with cleft lip/palate-mutation PVRL 1, encoding a
cell to cell adhesion molecule.
 Reduction in number of sweat gland, hair folicles, and
sebaceous gland.
 Salivary gland may show ectasia of ducts and inflammatory
changes.

48. Clinical Features
 A male predominance is usually seen.(X-linked inheritance pattern).
 Affected individuals typically display heat intolerance because of reduced
number of sweat glands.
 Rarely death occurs from the markedly elevated body temperature.
 Fine, sparse, blond hair Reduced density of eyebrow and eyelash hair.
 The periocular skin may show a fine wrinkling with hyperpigmentation.
 Midface hypoplasia resulting in protrubent lips.
 Xerostomia because salivary glands are ectodermally derived.
 The nails may also appear dystrophic and brittle.

50. HISTOLOGY
 Shows a decreased number of sweat gland and hair
follicles.
 Adenexal structure are hypoplastic and malformed.
TREATMENT
 Genetic counseling for parents and the patient.

51. NEUROCUTANEOUS SYNDROMES

52. NEUROFIBROMATOSIS
 Autosomal dominant condition, affect about 1 in
3000 people.
 There are many types, the most imortant two are:
1. Von Recklinghousen’s neurofibromatosis (NF1)
which accounts for 85% of cases.
2. Bilateral acoustic neurofibromatosis.

53. CLINICAL FEATURES
VON RECKLINGHOUSEN’S NEUROFIBROMATOSIS
 Six or more caf’e au lait patches (light brown oval macules),
usually developing in the first year of life.
 Axillary freckling in two thirds of affected individuals.
 Variable number of skin Neurofibromas
 Neurofibromas may not appear until puberty and become
larger and more numerous with age.
 Small circular pigmented hamartomas of the iris- Lisch
nodules.

54. Criteria for Diagnosis
 The presence of 2 or more of these criterias is
diagnostic.
1. 6 or more café au lait macules of >5mm in
prepubertal & >15mm in postpubertal
2. 2 or more neurofibromas or one plexiform
neurofibroma.
3. Freckling in axilla or perineum
4. Optic glioma
5. 2 or more lisch nodules
6. Distinctive bony lesion
7. A 1st degree relative with ND-1 by these criteria.

55. BILATERAL ACOUSTIC
NEUROFIBROMATOSIS (NF2)
 Bilateral acoustic neuromas
 Few,if any, cutaneous manifestation
 No lisch nodules
 Other features include tumours of CNS specially
meningiomas and gliomas.

59. TREATMENT
 There is no cure for the condition so the only therapy
for the patient with neurofibromatosis is to manage
symptoms or complications.
 Surgery may be needed when the tumours
compress organs or other structures.
 Less than 10% of people develop cancerous
growths, in these cases, chemotherapy may be
successful
 Genetic screening and counselling for families with
neurofibromatosis.

60. TUBEROUS SCLEROSIS
 BOURNEVILLE-PRINGLE SYNDROME
 Autosomal dominant condition, affected about 1 in
12000 children under 10 years.
 Two third of the cases are sporadic.
 It is characterized by triad of skin lesions (usually
angiofibromas of face), mental retardation and
epilepsy

61. CLINICAL FEATURES
 Small oval white patches (ash leaf macules) occur in
80% of cases, important as they may be the only
manifestation at birth.
 Adenoma sebaceum (angio-fibroma), occur in 85% of
cases, they develop at puberty as pink or yellowish acne-
like papules on the face, often around the nose
 Peri-unugal fibromas occur in 50% of cases, develop in
adult life as pink sausage-like lesions emerging from the
nail fold.
 Connective tissue nevi (shangreen patches) are seen in
40% of cases. Cobblestone, yellow plaques often arise in
the skin over the base of the spine.

62.  SYSTEMIC FEATURES-
 Epilepsy
 Mental retardation
 Ocular sign, including retinal phakomas and
pigmentary abnormalities.
 Hyperplastic gums
 Gliomas and calcification of the basal ganglia
tumours
 Cystic lesion of lungs

65. HISTOPATHOLOGIC FEATURES
 Shows a non-specific fibrous hyperplasia
 A benign aggregation of delicate fibrous connective
tissue.
 Characterized by plump, uniformly spread fibroblsts
with numerous interspersed thin walled vascular
channels.
TREATNMENT AND PROGNOSIS
 The management of the seizure disorder with
anticonvulsant agent.
 Genetic counsilling.

66. DISORDERS WITH MALIGNANT POTENTIAL

67. XERODERMA PIGMENTOSUM
 Autosomal recessive disorder, characterized by the
defective repair of DNA after its damage by UV
radiation.
 Caused by defects in the excision repair and/ or
post-replication repair mechanism of DNA.
 Mutation in the epithelial cell occur, leading to the
development of skin cancers.
 Markedly increased tendency to sunburn.

68. CLINICAL FEATURES
 The skin is normal at birth
 Multiple freckles, roughness and keratosis on
exposed skin appear between the ages of 6 months
and 2 years.
 Photosensitivity increases thereafter.
 The atrophic facial skin shows telengiectases and
small angiomas.

69.  Many tumours develop on light-damaged skin; these
include BCC, SCC, Keratoacanthoma and malignant
melanoma.
 Many patient die brfore the age of 20 years.
 Eye problems are common and include photophobia,
conjunctivitis and ectropion.
 The condition may be associated with microcephaly,
mental deficiency, dwarfism, deafness and ataxia.

72. HISTOPATHOLOGIC FEATURES
 Histopathologic features of xeroderma pigmentosum are
relatively non specific.
 Cutaneous premalignant lesions and malignancies that occur
are microscopically indistinguishable from those observed in
unaffected patients.
TREATMENT
 To avoid sunlight and unfiltered fluorescent light
 To wear appropriate protective clothing and sunscreen.
 Topical chemotherapeutic agents (eg 5-fluorouracil) may be
used to treat actinic keratoses.

73. PEUTZ-JEGHERS SYNDROME
 Relatively rare but well recognized condition, having
a prevalence of approximately 1 in 20,000 births.
 The syndrome is generally inherited as an autosomal
dominant trait, although 35% of cases represent new
mutations.
 Mutation of a gene known as LKB1 which encodes
for a serine/ thteonine kinase.

74. CLINICAL FEATURES
 Usually develop early in childhood and involve the periorificial
areas (eg. Mouth, nose, anus, genital region)
 The lesion resemble freckles, but they do not wax and wane
with sun exposure.
 Oral lesions include 1-4 mm brown to blue-gray macules
primarily affect the vermilion zone, the labial and buccal
mucosa.
 The intestinal polups (The jejunum and ileum are most
commonly affected).
 Gastrointestinal adenocarcinoma develops in 2% to 3% of
affected patients.

76. HISTOPATHOLOGIC FEATURES
 Slight acanthosis of the epithelium with elongation of
the rete ridges.
 No apparent increase in melanocyte number is
detected by electron microscopy.
 But the dendritic process of the melanocyte are
elongated
 Furthermore the melanin pigment appears to be
retained in the melanocytes rather than being
transferred to adjacent keratinocyte.

77. TREATMENT AND PROGNOSIS
 Patients with Peutz-Jeghers syndrome should be
monitored for development of intussusception or
tumour formation.
 Genetic counseling is also appropriate.

78. BASAL CELL NEVUS SYNDROME
 Gorlin syndrome, nevoid basal cell carcinoma
syndrome
 Transmitted by autosomal dominant manner.
 Occurs due to mutation in PCTH-1 gene located in
long arm of chromosome 6.
 PCTH-1 acts as tumor suppressor molecule, inhibits
formation of TGF-Beta, acts as cell-cycle regulator.

79. CLINICAL FEATURES
MUTLTIPLE SYSTEM DEFORMITIES
 Skin- Multiple BCC
 CNS- Calcification of falx cerbri
 Skeletal system- Fused vertebra, bifid ribs
 Ocular- Hypertelorism, Exopthalmos
 Genitourinary- Ovarian cysts and fibroma
 CVS- Fibromas of heart
 Others- Medulloblastoma, fibroma and rhabdomysarcoma

80. Photograph of the patient showing multiple basal cell carcinomas of the face
and back.

81. TREATMENT
 All patients with basal cell nevus syndrome should see a
dermatologist for regular skin examinations so that basal cell
carcinomas can be treated when they are small.
 Treatments available for these tumors including cryotherapy,
photodynamic therapy, fluorouracil cream and imiquimod
cream.
 Some patients may require long term treatment with oral
retinoids such as isotretinoin or acitretin.
 Sun protection is vital to reduce the number of skin cancers.
 Avoid unnecessary radiation exposure from the environment,
investigative radiology, or radiotherapy treatment.

82. CONCLUSION
 The genetic mysteries underlying several common
genodermatoses solves by gene identification
strategies.
 Some innovative methods need to be elucidated at
the molecular level.
 The dermatologist should be familiar with
concomitant illness that is exhibited in dermatoses
so that he may either institute appropriate treatment
or refer the patient to the proper therapist.