27- Congenital/Genodermatoses Flashcards
X linked dominant Whorled pigmentation on trunk Preceded by vesicular and verrucous changes Appears in girls usually 4-6 weeks old Usually resolve by 1 year of age
Incontinentia pigmenti
Histo of incontinentia pigmenti
Vesicular stage:
Verrucous stage:
Hyperpigmented stage:
Vesicular- spongiosis with eosinophils
Verrucous- dyskeratotic cells within epidermis
Hyperpigmented- dermal melanophages (pigment incontinence)
Most frequently involved extra cutaneous manifestations in incontinentia pigmenti
Teeth-90%
Bones-40%
CNS- 33%
Eyes-35%
This X linked dominant disorder is an important cause of neonatal seizures and encephalopathy
Incontinentia pigmenti
A variant of incontinentia pigmenti that manifests as hypopigmentation
Autosomal dominant, no vesicular/verrucous stages
Higher CNS abnormalities
Polycystic kidney disease
Incontinentia pigmenti achromians
Treatment for incontinentia pigmenti
None
Usually fades by 2 years old
May have minimal residual pigmentation in adulthood
Differs from incontinentia pigmenti by being autosomal dominant and reticular pattern of pigmentation
Abnormal dermatoglyphics-absent ridges on fingerprint
Mutation in keratin 14
Naegeli- Franceschetti- Jadassohn syndrome
Ichthyosis of skin similar to colloidon baby
Hyperkeratotic “whirl and swirl” pattern on erythematous skin
Waxy, shiny skin with crushed eggshell configuration
Ichthyosis clears within first year
Chondrodysplasia punctata
Associated nail changes with chondrodysplasia punctata
Platonychia
Onychoschizia
Most common sex chromosome disorder
Klinefelter syndrome
Cause of hypercoagulable state in Klinefelter syndrome
Increased plasminogen activator inhibitor 1
Patients with Klinefelter’s are at increased risk of developing
SLE
Cancers( male breast, hematogenous, sarcoma)
Frequent heart condition in Turner syndrome
Coarctation of the aorta
Conditions that may mimic Turner syndrome
Escobar syndrome (multiple pterygium syndrome)- autosomal recessive
Noonan syndrome- autosomal dominant
Manifestations that suggest a RASopathy
Congenital heart defects
Severe feeding difficulty
Developmental motor delay
Hair and skin anomalies
Patients with RASopathies are at an increased risk for developing
SLE
Classic triad of tuberous sclerosis only present in minority of patients
Adenoma sebaceum
Mental deficiency
Epilepsy
Sebaceous Angiofibromas in cheeks, nose and forehead
Shagreen plaque
Koenen tumors (periungual angiofibroma)
Ash leaf macules
Tuberous sclerosis
Diagnosis for tuberous sclerosis
Woods light- ash leaf macules
Xray/CT UTZ MRI- calcified intracranial nodules
Fundoscopy- retinal tumors
Renal UTZ- renal angiomyolipoma
Hand and foot xray- bone cysts and sclerosis
Two gene mutations in tuberous sclerosis
TSC1- hamartin
TSC2- tuberin
Treatment of tuberous sclerosis
MTOR inhibitors (everolimus)- angiofibromas
Adenoma sebaceum- laser/dermabrasion
Autosomal dominant Neurofibromas Cafe au lait spots Giant pigmented hairy nevi Sacral hypertrichosis Cutis verticis gyrata Lisch nodules
NF1
Autosomal dominant
Bilateral acoustic neuromas
Absence of cutaneous lesions
NF2
NF2 patients are at greater risk of developing these tumors
Optic gliomas
Neurilemmomas
Meningiomas
Soft tumors that can be pushed down by light pressure (buttonholing)
Spindle cell proliferations with amphophilic myxoid stroma and mast cells
Proliferation of all supporting elements of nerve fibers
Neurofibromas
Virtually pathognomonic of NF1
Subcutaneous plexiform neurofibromas
Finding of how many cafe au lait macules measuring 1.5cm is diagnostic of NF1?
6 or more
Axillary freckling in NF1 is called _______ sign
Crowe’s sign
Patients with NF1 are four times more likely to develop malignancy than the general population
True or false
True
Children with NF1 are 200-500 times more likely to develop this cancer
Malignant myeloid disorders
NF1 and NF2 protein involved
Neurofibromin and merlin
Not listed in the criteria but the presence of these findings are strongly associated with NF1
Nevus anemicus
Xanthogranuloma
Glomus tumor
Best imaging procedure for px with evidence of hearing impairments or abnormal evoked responses in NF
MRI
May be confused with neurofibromatosis
PTEN mutation
Greater number of cutaneous lesions also have most extra cutaneous abnormalities
Disproportionate overgroth, cerebriform plantar hyperplasia hyperostosis vascular malformations
Proteus syndrome
Autosomal dominant
Retinal angioma, cerebellar medullary angioblastic tumors, pancreatic cysts, renal tumors and cysts
Usually no skin manifestations
Mutation of tumor suppressor gene at short arm of chromosome 3
Von Hippel Lindau Syndrome
Cerebellar ataxia
Oculocutaneous telangiectasia
Sinopulmonary infections
Other features: choreic and atheroid movement, pseudopalsy of eyes
Ataxia telangiectasia
Early death from ___________ occurs in >50% of ataxia telangiectasia patients
Bronchiectasis
Ataxia telangiectasia patients have marked _____deficiency with decreased lymphocytes and absent thymus
What type of immunoglobulin
IgA
Most common type of malignancy in ataxia telangiectasia
Lymphoma (B cell)
Leukemia
Breast
Diagnosis for ataxia telangiectasia
High AFP and carcinoembryonic antigen
Group of rare genetic disorders with formation of blisters in response to minor physical injury
Epidermolysis bullosa
Internal involvement in EB primarily seen in recessive dystrophic type and also in junctional type
Esophageal and laryngeal
What type of EB
EM- cleavage below basal lamina, anchoring fibrils are diminished or absent
Recessive dystrophic
Roof or base (antigen localization):
EB Simplex
Base
Roof or base (antigen localization):
Dystrophic EB
Roof
Roof or base (antigen localization):
Junctional EB
BP antigen- roof
Type 4 collagen- base
LDA1- base
Type of epidermolysis bullosa where the mucous membranes and nails are not usually involved
EB Simplex intermediate
Gene mutations in EB simplex produce abnormality in which keratins?
Keratin 5 and 14
Separation in EB simplex occurs in what layer of the skin
Basal cell layer
Variant of EBS with active blisters in circinate configuration
Milia may develop
Oral mucosa involved, nails may shed but regrow
EB Simplex, generalized severe
Autosomal recessive
Severe generalized blistering at birth and extensive denudation may be fatal within a few months
Sparing of hands, characteristic perioral and perinasal hypertrophic granulation tissue
Junctional EB, generalized severe
Separation of junctional EB occurs at the level of
Lamina lucida
Complete reepithelialization of Herlitz junctional EB can be achieved in
7-10 months
Dysplastic teeth are found in _____ EB while normal teeth are in ______ EB
Junctional
Dystrophic
Vesicles and bullae appear on extensor surfaces most pronounced in joints
Flesh colored scarlike lesions appear on trunk
Healing with scarring and atrophy
Mucous membranes involved
Dystrophic EB
In dystrophic EB, cleavage occurs at the level of
Beneath basal lamina
Clinical variant of dystrophic EB where there are mechanoblisters and nail deformities
Associated with mandibulofacial dysostosis, renal aplasia and congenital abnormalities of lower extremities
Bart syndrome
Autosomal recessive, shares some features with dystrophic EB
Skin fragility with blistering, acral bullae, generalized poikiloderma with atrophy
Photosensitivity, acral keratoses, periodontal disease and phimoses
Acrokeratotic poikiloderma
Principal histologic change in acrokeratotic pokiloderma:
Absence of elastic fibers in _______ dermis and fragmented fibers in ______ dermis
Papillary
Mid
Trauma induced skin fragility and defects of hair, nails and sweat glands
Blisters noted on pressure points especially after prolonged standing or walking
Mutation in PKP1 gene
McGrath syndrome
Ectodermal dysplasia/ skin fragility syndrome
Generalized and mucosal blistering
Mittenlike deformity- digital fusion with encasement in scar tissue
Dental complications, esophageal strictures
Anemia and growth retardation
High risk of developing SCC
Recessive dystrophic EB, generalized severe
Persistently recurrent macerated plaques with a reticulated pattern of fissuring in flexural areas
May resemble impetigo
ATP2C1 gene
Acanthosis and full thickness acantholysis resembling a dilapidated brick wall
Hailey Hailey disease
Familial benign chronic pemphigus
Autosomal dominant
Fine scales that appear pasted on body
Coarser scales on lower extremities, extensor surfaces most involved
Hyperkeratosis of palms, keratosis pilaris
Improves in adulthood
Ichthyosis vulgaris
Histo: compact eosinophilic orthokeratosis
Granular layer reduced or absent
Keratohyalin granules appear spongy or fragmented
Ichthyosis vulgaris
Type of ichthyosis due to steroid sulfatase deficiency
Associated with CS birth
Dark large scales prominent in anterior neck, extensors, trunk (abdomen more involved)
Dramatic clearance in summer
Does not improve with age
X linked icthyosis
Autosomal recessive ichthyosis present at birth
Collodion like membrane, desquamation over 2-3 weeks of life
Grayish brown scales
Follicles have crateriform appearance
Ectropion present
Lamellar ichthyosis
Lamellar ichthyosis px have decreased or absent
TGM1- transglutaminase 1 activity
Born enclosed in a parchment/collodion like membrane
Ectropion of eyelids
Within 24 hours of birth, fissuring and peeling cast off in 10-14 days with rapid improvement, left with redness and scaling
Non Bullous congenital ichthyosiform erythroderma
Ichthyosiform erythroderma is associated with what disease
Neutral lipid storage disease
Disorder that affect the skin in utero
Thick, horny, armorlike plates covering surface
Rudimentary/absent ears, eclabium, entropion
Child stilborn
Harlequin fetus
Blisters at or shortly after birth
Thickened, horny or spinelike ridged scales later
Prominent at flexures
Mutation in genes for K1 and K10
Less severe with age
Epidermolytic ichthyosis/hyperkeratosis
Treatment of epidermolytic hyperkeratosis
High dose vitamin A 750,000U daily x 2 weeks
Systemic retinoids
Lack of erythema
Mild hyperkeratosis limited to flexures
Superficial mottling/peeling (“mauserung phenomenon “)
Ichthyosis bullosa of Siemens
Acquired ichthyosis can be due to
Hodgkin/non hodgkin disease Hypothyroidism Sarcoidosis Hansen, AIDS, LE, dermatomyosistis Drugs: nicotinic acid, statins
Abnormal facies, tight skin, sparse eyelashes and secondary joint changes
Associated with polyhydramnios, reduced fetal movement and premature delivery
Restrictive dermopathy
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