Transcript Genodermatosis Part II Chapter 27 - Andrews Boris Ioffe, D.O. KCOM-Texas Division 06-27-06 Rud Syndrome • Ichthyosis, hypogonadism, small stature, MR, acanthosis nigricans, epilepsy, macrocytic anemia • Autosomal.

Genodermatosis Part II
Chapter 27 - Andrews
Boris Ioffe, D.O.
KCOM-Texas Division
06-27-06
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
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
KID Syndrome
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
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
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.
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.
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
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
Porokeratosis
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
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
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
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
Darier’s Disease
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
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
Acrokeratosis Verruciformis
• AD
• 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
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
Pachyonychia Congenita
• Types
– Type I JadassohnLewandowsky – most
common
– Type II Jackson-Sertoli
similar to type I with
natal teeth and
steatocystoma
multiplex
• Less severe
keratoderma
• Absence of oral lesions
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
•
•
•
•
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
Dyskeratosis Congenita
• Zinsser-Cole-Engman
syndrome
• Cutaneous poikoloderma,
nail dystrophy and
premalignant leukoplakia
• Atrophy and
telangectasia
accompanied by mottled
hyper- and hypopigmented macules
• Nails may be thin and
dystrophic
• Leukoplakia on oral
mucosa
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
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
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)
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
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
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
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.
Ectodermal Dysplasias
• Other syndromes
– Odonto-Tricho-Ungual-Digital-Palmar
Syndromes
– Costello Syndrome
– Lenz-Majewski Syndrome
– CHIME Syndrome
– Lelis Syndrome
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)
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
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
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
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
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
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
www.xps.org
Skin tumors have mutations in ras, p53 and ptch gene
Xeroderma Pigmentosum
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
• Xeroderma Pigmentosum/Cockayne
Syndrome Complex
– Skin features of XP and neurologic features of
Cockayne syndrome
– Complementation groups B, D, and G
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
Trichothiodystrophy
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
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
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
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
Other Syndromes
•
•
•
•
•
•
•
Treacher Collins Syndrome
Popliteal Pterygium Syndrome
Van Der Woude Syndrome
Apert Syndrome
Pfeiffer Syndrome
Crouzon Syndrome
Whistling Face Syndrome
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
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
Syndromes that include
abnormalities of the hair
• Crow-Fukase(POEMS) syndrome
– Polyneuropathy, organomegaly, endocrinopathy, Mprotein, and skin changes
•
•
•
•
•
•
Cartilage-Hair Hypoplasia
Tricho-Rhino-Phalangeal Syndrome
Papillon-Lefevre Syndrome
Kippel-Feil Syndrome
McCusick Syndrome
Atrichia with Papules
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
Keratosis Pilaris
• Treatment
– Difficult
– 12% ammonium
lactate causes
smoothing but does
not reduce erythema
– Topical calcipotriene
– Topical retinoids
– Topical salicylic acid or
urea
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
Keratosis Pilaris Atrophicans
• Three syndromes
– Keratosis pilaris atrophicans facei
– Atrophoderma vermiculata
– Keratosis pilaris follicularis spinulosa
decalvans
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
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
• 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