1. Genodermatosis Part II Chapter 27 - Andrews
Boris Ioffe, D.O.
KCOM-Texas Division

2. Rud Syndrome
Ichthyosis, hypogonadism, small stature, MR, acanthosis nigricans, epilepsy, macrocytic anemia
Autosomal recessive inheritance in most cases
Maybe a variant of Sjorgen-Larsson syndrome or Refsum syndrome

3. Keratitis-Ichtyosis-Deafness Synrome
Aka Senter syndrome
Vascularization of the cornea, extensive congenital ichthyosiform eruption, neurosensory deafness, reticulated hyperkeratosis of the palms and soles, hypotrichosis, partial anhidrosis, nail dystrophy and tight heel cords
Distinctive leathery verrucoid plaques involving central portion of the face and ears
Missense mutation in GJB2 gene, most cases sporadic
Isotretinoin may exacerbate and promote corneal vascularization, not with acitretin

4. KID Syndrome

5. Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects Syndrome
CHILD Syndrome
Unilateral inflammatory epidermal nevi and ipsilateral limb hypoplasia or limb defect
Features vary widely
X-linked dominant
NSDHL gene on Xq28 chromosome
Suspect when unilateral epidermal nevi shows features of verruciform xanthoma

6. Erythrokeratodermia Variabilis
Aka erythrokeratodermia figurata variabilis and Mendes da Costa type erythrokeratodermia AD
Erythematous patches and hyperkeratotic plaques of sparse but generalized distribution
Change shape or size and may involute completely
50% of patient’s display a palmoplantar keratoderma associated with peeling
Systemic retinoids

7. Acquired Ichthyosis Similar to ichthousis vulgaris Systemic diseases
Hodgkin’s disease
NHL, MF, MM, and carcinomatosis
Sarcoidosis, especially over the lower extremities
Others: leprosy, nutritional deficiency, AIDS, human T-cell lymphocytic virus, LE, etc.

8. Pityriasis Rotunda
Perfectly circular scaly patches on the torso and proximal portions of the extremities
Scale is adherent and resembles that of icthyosis vulgaris
Ethnic predisposition to blacks, Japanese, Koreans, and Italians, some association with systemic disease
DDx: TV, tinea corporis, erythrasma, leprosy, fixed drug eruption, and pityriasis alba
TX: emollients, topical and systemic steroids.

9. Porokeratosis AD, heterogenous group of disorders
Distinct finding of keratotic ridge with central groove that corresponds to coronoid lamella on histology
May be accenuated by gentian violet, povidone iodine or permanent markers
TX: Topical 5-FU, topical retinoids, vitamin D3 analogues, oral retinoids

10. Plaque-Type Porokeratosis
Mibelli
Chronic, progressive dz with formation of slightly atrophic patches surrounded by an elevated, warty border
Spreads peripherally
Surfaces of the hands and fingers and the feet and ankles
Histology: coronoid lamella, a column of parakertotic keratin extending 45 degrees from a focus of dyskeratotic cells

11. Porokeratosis

12. Disseminated Superficial Actinic Porokeratosis(DSAP)
Numerous superficial, annular, keratotic, brownish-red macules on sun exposed areas
More common in women
Exacerbations occur during summer, also in immunosupressed patients
Gene loci have been localized to chromosomes 12 and 15

13. Linear Porokeratosis Segmental or generalized
Maybe identified during newborn period when it follows lines of Blaschko
Ulcerations and erosions may delay the diagnosis
Highest risk of developing cutaneous malignancies
SCC, Bowen’s disease and BCC

14. Porokeratosis Palmaris, Plantaris et Disseminata
Lesions first appear on palms and soles
Onset in 20s
May slowly extend over the entire body
May be part of the porokeratotic eccrine ostial and dermal duct nevus

15. Darier’s Disease Aka Keratosis Follicularis, Darrier-White Disease AD
Brown keratotic papules that coalesce into patches in seborrheic distribution
Each papule becomes covered with greasy, gray-brown crust that fits into a small concavity in the summit of the papule
Neck, shoulders, face, extremities, front of the chest, midline of the back – sites of prediliction
Early lesions are frequently behind the ears
Worse in the summer
Induced by lithium carbonate
Disseminates herpes simplex may be a complication

16. Darier’s Disease

17. Darier’s Disease ATP2A2 gene encoding calcium ATPase
Impairs trafficking of desmoplakin, contributing to acatholysis
Histo
Acantholytic dyskeratotis with overlying hyperkeratosis
Corp ronds and grains

18. Darier Disease Treatment
Topical antibacterials, oral antibiotics and short-term application of corticosteroid may benefit
Oral retinoids are drugs of choice
Cyclosporin for sever flares
Topical sunscreens and ascrobic acid
Photodynamic therapy has been tried

19. Acrokeratosis VerruciformisAD
Numerous flat verrucous papules occuring on the back of the hands, insteps, knees and elbows
Closely grouped and resemble warts
Verrucous lesions identical to Darier
Histo
Hyperkeratotis, thickening of the granular layer and church spire papillomatotis

21. Pachonycia Congenita
Thickened nailbeds of all fingers and toes, palmar and plantar hyperkeratosis, blistering under the callosities, palmar and plantar hyperhidrosis, spiny follicular keratoses, and benign leukokeratosis of the mucous membranes
Nailbed is filled with yellow, horny, keratotic debris, which may cause nail to project upwards
Painful friction blisters may develop on the plantar aspects of toes

22. Pachyonychia Congenita
Types
Type I Jadassohn-Lewandowsky – most common
Type II Jackson-Sertoli similar to type I with natal teeth and steatocystoma multiplex
Less severe keratoderma
Absence of oral lesions

23. Pachyonychia Congenita
Type III
Schafter-Branauer
Leukokeratosis of corneas
Type IV
Pachyonychia congenita tarda
Hyperpigmentation around the neck, waist, axillae, thighs and flexures of knees

24. Usually inherited in as an AD trait Type I – keratin 6a and 16
Type II – keratin 6b and 17 TX
Avulsion of the nails
Destruction of the nail matrix with phenol
Topical lactic acid, ammonium lactate, salycilic acid or urea for keratoderma
Isotretinoin for keratotic papules and oral leukokeratosis
Acitretin for late-onset form

25. Dyskeratosis Congenita
Zinsser-Cole-Engman syndrome
Cutaneous poikoloderma, nail dystrophy and premalignant leukoplakia
Atrophy and telangectasia accompanied by mottled hyper- and hypo-pigmented macules
Nails may be thin and dystrophic
Leukoplakia on oral mucosa

26. Dyskeratosis Congenita
Other manifestations:
Hyperhydrosis of palms and soles, bullous conjunctivitis, gingival disorders, dysphagia resulting from esophageal strictures and diverticula
Fanconi anemia
Defect for X-linked form located on Xq28 with DKC1 gene
G-CSF and erythropoetin for bone marrow failure
Bone marrow transplantation

27. Fanconi Syndrome Aka familial pancytopenia or familial panmyelopthisis
Diffuse pigmentation of the skin, absence of thumbs, aplasia of the radius, severe hypoplastic anemia, thrombocytopenia, retinal hemorrhage, strabismus, generalized hyperreflexia
Increased risk of leukemia, SCC and hepatic tumors
Autosomal-recessive with multiple genes involved

28. Ectodermal Dysplasias
Heterogeneous group of genodermatosis with abnormal, absent, incomplete or delayed development during embryogenesis of one or more of epidermal or mucosal appendeges(hair, sebaceous glands, nails and teeth)

29. Hypohidrotic Ectodermal Dysplasia
Classic triad
Hypotrichosis, anodontia, and hypohydrosis
Eccrine glands are absent or rudimentary
Facies suggestive of congenital syphillis
X-linked recessive
EDA1, EDAR, and EDARADD genes
If linked with immuno defeciencies than NF-kappaB modulator, NEMO and inhibitor kappaB kinase

30. Hidortic Ectodermal Dysplasia
Clouston syndrome AD
Eccrine sweat glands function normally and facial features are normal
Alopecia, nail dystrophy, palmoplantar hyperkeratosis and eye changes such as cataracts and strabismus
May be similar to pachyonychia congenita

31. Ectodermal Dysplasias
AEC Syndrome(Hays-Wells)
Ankyloblepharon, ectodermal defects and cleft lip or palate
Sparse hair, dental defects, dystrophic nails, hypospadias, syndactyly, etc.
Erosive scalp dermatitis
EEC Syndrome
Ectodermal dysplasia, ectrodactyly(congenital absence of all or part of digits), and cleft lip/palate

32. Ectodermal Dysplasias
Rapp-Hodgkin Ectodermal Dysplasia Syndrome
Anomalies of hair, cleft lip/palate, onychodysplasia, dental caries, hypodontia, craniofacial abnormalities, hypohydrosis, otitis media and hypospadias
Ectodermal Dysplasia with Corckscrew Hairs
Margarita Island of Venezuela
Corkscrew hair, scalp keloids, follicular plugging, KP, xerosis, eczema, PPK, syndactyly, etc.

33. Ectodermal Dysplasias
Other syndromes
Odonto-Tricho-Ungual-Digital-Palmar Syndromes
Costello Syndrome
Lenz-Majewski Syndrome
CHIME Syndrome
Lelis Syndrome

35. Pachydermoperiososis
Thickening of skin in folds and accentuation of creases on the face and scalp, clubbing of fingers and periostosis of long bones
Thickening of the ears and lips, enlargement of the tongue, thickening of the scalp
Inherited and acquired forms
Acquired forms with chronic pulmonary, mediastinal and cardiac diseases(bronchogenic carcinoma)

36. Cutis Verticis Gyrata
Folds and furrows on the scalp, usually in anterioposterior direction
Primarily males, onset at puberty , maybe a part of pachydermoperiostosis if familial
Associated with
Developmental anomalies, inflammation, trauma, tumors, nevi, amyloidosis, syphillis, myxedema, Ehlers-Danlos, Turner, Klienfelter, fragile X syndrome, and insulin resistance syndrome
Also seen in MR, seizures and schizophrenic patients

37. Aplasia Cutis Congenita
Predeliction for midline of the vertex of the scalp
Absences of skin and rarely full-thickness defect of the cranium
Associated with thyroid disease and thyroid medications
“hair collar sign” ring of dark, long hair encircling the lesion

38. Focal Dermal Hypoplasia
Goltz Syndrome
Abnormalities in mesodermal and ectodermal tissues
Reddish-tan, atrophic, often linear or cribiform patches are commonly present on the buttocks, axillae and thighs
Lipocytes accumulate in the lesions in nevoid fashion
80% have skeletal defects
40-50% dental abnormalities
Scoliosis, spina bifida and hypoplasia of the clavicle

39. Werner Syndrome Adult Progeria Premature aging syndrome
Many metabolic and structural abnormalities affecting numerous organs
Cells demonstrate genomic instrability
Diagnosed in middle age, die before 50
Senile cataracts, premature balding and graying, scleroderma-like lesion on the skin
Loss of subcutaneous tissue and muscle wasting
Osteoporosis and aseptic necrosis
Skin – poikiloderma, scleroderma, atrophy, hypekeratoses and leg ulcers
High rate of malignancy

40. Progeria Hutchinson-Gilford Syndrome
Accelerated aging, dwarfism, alopecia, generalized atrophy of the skin and muscles, enlarged head with prominent scalp veins and high incidence of atherosclerosis
Death by second decade
Mutations in LMNA

41. Xeroderma Pigmentosum
Autosomal-recessive
Defective DNA thymidine dimer excision repair
Extreme sun sensitivity, freckling, and skin cancers
Skin cancers appear before age 10
Ocular abnormalities – ectropion, corneal opacity, and neoplasms
Retinoids can prevent appearance of new cancers
Photo-protection essential management
Gene therapy is being pursued
Skin tumors have mutations in ras, p53 and ptch gene

42. Xeroderma Pigmentosum

43. Cockayne Syndrome Sun sensitivity and neurologic degeneration
No freckling and skin ca
Dwarfism, beaked nose, loss of subcutaneous tissue, deafness, basal ganglia calcification, and retinopathy
Dwarfism with retinal atrophy and deafness
Mutations in XPB or XPD DNA helicases can result in XP, Cockayne syndrome or trichothiodystrophy

44. Xeroderma Pigmentosum/Cockayne Syndrome Complex
Skin features of XP and neurologic features of Cockayne syndrome
Complementation groups B, D, and G

45. Trichothiodystrophy
Photosensitivity, itchthyosis, brittle hair, intelectual impairment, decreased fertility, and short stature(PIBIDS)
Similar to Tay syndrome plus photosensitivity
No increase in skin cancers
Hair has decreased sulfur content of 50%
Polarized light shows alternating dark and bright regions
Light microscophy – trichoschisis and trichorrhexis nodosa

46. Trichothiodystrophy

47. Bloom Syndrome Bloom-Torre-Machecek Syndrome AR, eastern European Jews
Photosensetive telangiectatic erythema in the butterfly area of the face and dwarfism
Resemble LE and develop in first 2 years
Café-au-lait spots, itchthyosis, acanthosis nigricans, syndactyly, irregular dentition, prominent ears
Increased frequency of cancers of all cell types
BLM gene coding for RecQ DNA-helicase

48. Rothmund-Thomson Syndrome
Poikiloderma congenitale
Poikiloderma beings at 3 to 6 months of age with tense, pink, edematous pathces on the cheeks, hands, feet and buttocks
Sensitivity to sunlight
Fine reticulated or punctate atrophy associated with telengectasias
Broad range on noncutaneous lesions
Mutations in RECQ4L gene

49. Hereditary Sclerosing Poikiloderma and Mandibuloacral Dysplasia
Poikiloderma in childhood
Hypekeratotic and clerotic cutaneous bands extending across antecubital spaces, axillary vaults, and popliteal fossa
Aortic stenosis, clubbing of fingers, and localized calcinosis
No Treatement
Weary has reported several cases of Mandibuloacral Dysplasia

50. Other Syndromes Scleroatrophic syndrome of Huriez
Scleroatrophy of hands with sclerodactyly
Ridging, clubbing, or hypoplasia of nails
Lamellar keratoderma of hands and soles
Franceschetti-Klein Syndrome
Palbebral antimongoloid fissures, hypoplasia of facial bones, macrostomia, vaulted palate, malformation of both the external and internal ear, buccal-auricular fistula

51. Other Syndromes Treacher Collins Syndrome Popliteal Pterygium Syndrome
Van Der Woude Syndrome
Apert Syndrome
Pfeiffer Syndrome
Crouzon Syndrome
Whistling Face Syndrome

53. Syndromes that include abnormalities of the hair
Hallerman-Streiff Syndrome
“bird facies”, congenital cataracts, micropthalmia, hypotrichosis and dental abnormalities
Nose is thing,sharp and hooked and the chin is absent
Hair is diffusely sparse and brittle
Baldness frontally or at the scalp margins
Polyostotic Fibrous Dysplasia(Albright’s Disease)
Slowly progressive lifelong unilateral hair loss

54. Syndromes that include abnormalities of the hair
Cronkhite-Canada Syndrome
Alopecia, skin pigmentation, onychodystrophy, malabsorption and generalized GI polyposis
Marinesco-Sjogren Syndrome
Trichothiodystrophy
Generalized Trichoepitheliomas
Alopecia and myasthenia gravis

55. Syndromes that include abnormalities of the hair
Crow-Fukase(POEMS) syndrome
Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes
Cartilage-Hair Hypoplasia
Tricho-Rhino-Phalangeal Syndrome
Papillon-Lefevre Syndrome
Kippel-Feil Syndrome
McCusick Syndrome
Atrichia with Papules

57. Keratosis Pilaris
Mild cases are limited to posterior upper arms, thighs the next most common site, may occur on the face, buttocks, trunk and legs
Facial involvement may be confused with acne
Individual lesions are small, acuminate, follicular papules with keratotic plug, erythema may be present
Prone to appear in xerotic or atopic patients
AD inheritance
Other associated conditions:
Ichthyosis vulgaris, atrichia with papular lesions, mucoepidermal dysplasia, cardiofacio-cutaneous syndrome, ectodermal dysplasia with corkscrew hair, and KID syndrome

58. Keratosis Pilaris Treatment Difficult
12% ammonium lactate causes smoothing but does not reduce erythema
Topical calcipotriene
Topical retinoids
Topical salicylic acid or urea

59. Follicular Atrophoderma
Follicular indentations without hairs, notably occuring on extensor surfaces of hands, legs, and arms
Scrotal tongue
Associated with:
X-linked dominant chondrodysplasia punctata, Bazex syndrome and keratosis palmoplantaris disseminata

60. Keratosis Pilaris Atrophicans
Three syndromes
Keratosis pilaris atrophicans facei
Atrophoderma vermiculata
Keratosis pilaris follicularis spinulosa decalvans

61. Keratosis Pilaris Atrophicans Faciei and Ulerythema Ophryogenes
Persistant erythema and small horny follicular papule with onset during childhood
On involution these leave pitted scars and atrophy resulting in alopecia
Involves eyebrows and neighboring scalp
May begin on cheeks and temple
Histo – follicular hyperkeratosis of the upper third of the follicle
Maybe seen in atopy and Noonan syndrome

62. Atrophoderma Vermiculata
Symmetricla involvement of the face by numerous closely crowded small areas of atrophy separated by narrow ridges producing cribiform or honeycomb surface
Worm-eaten(vermiculate) appearance
Cause is undertermined
Skin covering the ridges is even with normal skin

63. Keratosis Follicularis Spinulosa Decalvans(Siemens-1 Syndrome)
Rombo syndrome
Atrophodermia vermiculata, cyanosis of hands and feet, milia, telangectases, hypotrichosis, multiple BCCs, and trichoepitheliomas
Keratosis Follicularis Spinulosa Decalvans(Siemens-1 Syndrome)
KP begins on the face and progresses to scalp, limbs and trunk
Cicatricial alopecia
Associated with atopy, photophobia, and corneal abnormalities
Deafness, physical and mental retardation, recurren infections, nail abnormailites and aminoaciduria