1. Disclosure
• Novartis pharmaceuticals (clinical trial)
• Taro pharmaceuticals (previously a
Cutaneous Manifestations of
speaker and consultant)
Genetic Diseases
• Sciele pharmaceuticals (consultant)
• Asst Professor at Arizona State University
NAPNAP 2008
Judith O’Haver PhD, RN, CPNP
Objectives Cutaneous Mosaicism
• Recognize the different patterns of
• The definition of Mosaicism
mosaicism as it relates to cutaneous
– “an organism composed of 2 or more
manifestations of genetic diseases in
genetically different population of cells
children.
originating from 1 genetically homogenous
• Recognize the cutaneous manifestations zygote” (Happle and Konig, p.368)
of selected genetic conditions – Skin is often a reflection of these conditions
• Be able to identify the course of action for
the cutaneous manifestation of selected
genetic conditions in children
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2. Types of Cutaneous Mosaicism Lines of Blaschko
• Blaschko lines • The lines can be narrow or broad
– Checkerboard pattern • The configuration is based on the
outgrowth of embryonic cells from the
– Phylloid pattern
neural crest
– Patchy pattern without midline separation
– Lateralization • There is a characteristic pattern that arises
– It is probable that others will be defined in the as a result of the growth of the embryo in
future conjunction with this proliferation of cells
May be further defined…. Case 1
• Functional X chromosome mosaicism • 4 year old male is referred to your clinic
with a history of brown adherent scaly skin
• Autosomal epigenetic mosaicism
that waxes and wanes depending on the
• Genomic mosaicism
weather
• The child was born by C-section after
failure to progress
• Reported cradle cap as an infant
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3. X linked Recessive Ichthyosis Diagnostic features in children
• There is an absence of steroid sulfatase due to a • Brown adherent scale
gene deletion (Xp22.32) or contiguous gene
• May affect the eyes (comma shaped
deletion syndrome
corneal opacities)
• In female carriers this absence leads to perinatal
problems such as delayed onset of labor and • Males may have cryptorchidism (20%)
failure to progress
• Cutaneous involvement waxes and wanes
• May be diagnosed prenatally
throughout life-may be worse in the dry
• The neonates often present with a diffuse
weather
erythema and exfoliation
• Usually present at 2-6 weeks of age
Management Case 2
• Newborns • A female is born with a rash that is
– -monitor fluid and electrolytes, protein intake partially vesicular on an erythematous
and temperature base
– -more at risk for infection
• It is primarily in a linear pattern on the
• Dermatology referral (usually managed
child’s leg
with topical treatment)
• The child was born after a term healthy
• If needed refer to pediatric urology
pregnancy and does not appear ill
• Referral to pediatric opthalmology
• Advise OB-GYN in future pregnancies
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4. Incontinentia Pigmenti
4 stages
(Bloch-Sulzberger syndrome)
• I-Vescicular
• This is an X linked dominant disorder that
– occurs in the first few weeks to about 4 months of life
is usually lethal to males
– may present at birth
– -male survivors may also have Klinefelter
– Appears as blisters or pustules on an erythematous
syndrome
base or erythematous macules and papules in the
• Presents in a Blashko line distribution Blashko line distribution
which distinguishes it from other newborn • II-Verrucous
rashes – Usually seen about 1 month of age and consists of
warty lesions that are usually red brown and scaly
– Resolves by 4-6 months
Diagnosis and Treatment
• III-Hyperpigmentation • Biopsy confirms the diagnosis
– Usually 3-6 months • Consult ophthalmology and genetics and
eventually dental
– Linear and whorls and swirls
hyperpigmentation that may persist for years
• Additional evals pending symptoms
along Blaschko lines
• Symptomatic treatment as needed for the
• IV-Hypopigmentation
lesions
– Hypopigmented atrophic streaks (adulthood)
• Prognosis is a normal life span
may be associated with or without follicular
atrophy
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5. Case 3 Neurofibromatosis
• Child presents to clinic for evaluation of • There are 3 types of NF
increasing numbers of café au lait macules • Type 1 and 2 are autosomal dominant and
• Family history suggests that no other occur spontaneously 50% of the time
members of the family have multiple • Types 3-8 appear to be partial forms of
lesions type 1 and 2
• Child is otherwise well and
developmentally normal
Neurofibromatosis Neurofibromatosis Type 1
• Type 1 (von Recklinghausen Disease) • Clinical features:
• The gene responsible is on chromosome 17 – Café au lait macules (increase in size and number in
(17q11.2) and encodes the protein the first 5 years of life)
neurofibromin (90%)
– Two or more neurofibromas (any type) or 1 or more
– Usually appears in young children
plexiform neurofibromas
• Type 2 is (Acoustic Neuroma Syndrome)
– Axillary or inguinal freckling (90%)
• The gene responsible is located on the long arm
– Bilateral Optic nerve glioma
of chromosome 22 (22 q 11-13.1)and encodes
the protein merlin – 2 or more Lisch nodules (iris hamartomas)
– Usually appears in teens and young adults – Osseous lesions (skeletal dysplasia)
– Bilateral vestibular Schwannomas – First degree relative with NF
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6. Neurofibromatosis type 1
Diagnosis and Treatment
other features
• Macrocephaly • Made on clinical criteria
• Short stature • AAP has issued a policy statement on NF that
may assist in providing care for these children
• Scoliosis
and offer guidance for health maintenance
• Hypertension
• Management depends on symptoms but
• Learning disabilities children should be referred to genetics and
• ADHD ophthalmology, neurology and other specialists
as needed for SX
• Mental retardation (rare about 5%)
• Prognosis is dependant on involvement
• Increased risk of malignancy
Monitor for…. Case 4
• Pain • Infant presents to clinic with multiple
hypopigmented macules and multiple café
• Plexiform neurofibromas
au lait macules
• Changes in visual acuity
• Family history is non-contributory
• HA
• Hypertension • Infant is otherwise healthy and appears
normal
• Scoliosis
• Abnormalities of long bones
• Refer as needed
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7. Tuberous Sclerosis Complex
Manifestations
(Bourneville’s Syndrome)
• Neurocutaneous syndrome • Hypomelanotic macules appear usually
• Mutations on 2 genes
early in life (ash leaf macule)
– TSC1 on chromosome 9 (9q34)
• Facial angiofibromas usually in nasolabial
– TSC2 on chromosome 16 (16pl3)
• Transmitted as an autosomal dominant trait, folds, cheeks or chin
may be a spontaneous mutation and parent may
• Shagreen patch
be asymptomatic
• May be diagnosed prenatally if the mutation is • Fibrous facial plaques
known
• Periungual fibromas
• May also note rhabdomyoma if fetal echo is
performed
• Café au lait macules
Other manifestations Diagnosis and Treatment
• Requires the presence of 1 major and 2 minor
• Neurological component
features
• Eyes (retinal hamartomas) • Treat symptomatically (ie. Sz)
• Kidney • Genetic counseling
• Includes multiple specialties
• Cardiac (rhabdomyoma)
– Neurology (MRI), neurodevelopmental testing
• Oral – Opthalmology
• Musculoskeletal – Cardiology (EKG, ECHO)
– Renal U/S
• lungs
– Pulmonology if symptomatic
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8. Prognosis Case 5
• Depends on organ involvement • Child presents to clinic with sparse hair,
abnormal dentition, frontal bossing, saddle
• CNS, cardiac and renal complications are
nose, supraorbital ridging and absent
the leading cause of morbidity and
eyebrows, hyperpigmentation in the orbital
mortality
area and thick lips. On history mother
reports this child does not sweat much.
Ectodermal dysplasia Anhidrotic Ectodermal Dysplasia
• More than one type • Usually X linked recessive (ectodysplasin
– Hypohidrotic ectodermal dysplasia (Christ- (EDA) gene (Xq12-q13)
Siemens-Touraine Syndrome)
• May be diagnosed prenatally
– Hidrotic ectodermal dysplasia (Clouston
• Ectodysplasin –defective regulation in the
syndrome)
ectodermal structures
– EEC syndrome (Ectrodactyly-Ectodermal
Dysplasia-Cleft lip palate syndrome)
• Hypohidrotic ED
– AEC syndrome (Ankyloblepharon filiforme
– Autosomal dominant
adenatum-Ectodermal Dysplasia-Cleft Palate-
– 2q11-q13
Hay Wells Syndrome
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9. Multiple structures affected Prognosis and nursing care
• Skin • Very important to avoid overheating and
treat infections and temps
• Hair
• May have dry mucosa and skin-treat with
• Nails
emollients
• Craniofacial
• Referrals to dental and plastic surgery
• Teeth
• ENT-prn
• Wig
• Usually have normal life span
Case 6 Epidermolysis Bullosa
• Rare genetic skin disease
• Nursery consult of an infant born with
large blisters after a vaginal delivery • Vesicles and bullae in response to friction
• 3 general categories
• Negative for infectious disease
– Epidermolysis bullosa simplex
• Not currently ill or on any medications
• Weber-Cockayne
• Köebner
• Dowling-Meara
– Junctional EB (JEB)
– Dystrophic EB
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10. Epidermolysis Bullosa Simplex Junctional EB
• Autosomal dominant • Herlitz
• Defect in the keratin gene (K5 12q, K14 • Junctional EB with pyloric atresia
17q) • Non—Herlitz JEB
• Weber-Cockayne • Other variants
• Koebner
• Dowling-Meara
Dystrophic EB Diagnosis and Treatment
• Biopsy to make diagnosis-sent for
• Dominant (Cockayne-Touraine’s Disease)
histopathology, immunomapping and electron
• Recessive (Hallopeau-Siemens variant) microscopy
• DNA analysis
• Prenatal diagnosis is possible
• Treatment is supportive
– Pain control
– Wound management
– Nutritional support
– Social support
• Prognosis depends on the type
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11. Summary References
• Dermatlas.com
• Role of genetics in recognizing cutaneous
• Fitzpatrick, T.B., Johnson, R.A., Wolff, K., & Suurmond,
manifestations of selected conditions D. (2001). Color Atlas and Synopsis of Clinical
Dermatology (4th ed.) New York: McGraw Hill.
• Suggestion of resources for further
• Happle, R. Cutaneous Mosaicism (2003). In L.A.
information Schachner & R.C. Hansen (eds.) Pediatric Dermatology
(3rd edition). Edinburgh: Mosby.
• johaver@phoenixchildrens.com
• Itin, P.H., Burgdor, W.H.C., Happle, R., Paller, A., Konig,
A., Pierini, A., Lenane, P., Krafchik, B., Korf, B., Orlow,
S., Mallory, S., Eady, R., & McGrath, J. (2003).
Genodermatosis. In L.A. Schachner & R.C. Hansen
(eds.) Pediatric Dermatology (2003). (3rd edition).
Edinburgh: Mosby.
More references…
• Krowchuk, D.P. & Mancini, A.J. (Eds.), Pediatric
Dermatology: A Quick Reference Guide. American
Academy of Pediatrics.
• Richard, C., Moss, C., Traupe, H., Pittelkow, M.,
Lautenschlager, S., Konig, A., Happle, R., & Iten, P.
(2003). Ichthyosis and Disorders of Cronification. In L.A.
Schachner & R.C. Hansen (eds.) Pediatric Dermatology
(3rd edition). Edinburgh: Mosby.
• Spitz, J.L. (2005). Genodermatoses (2nd ed.).
Philadelphia: Lippincott Williams & Wilkins.
• Tidman, M.J. & Garzon, M.C. (2003). Vesiculobullous
Disease. In L.A. Schachner & R.C. Hansen (eds.)
Pediatric Dermatology (3rd edition). Edinburgh: Mosby.
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