Transcript PowerPoint Presentation - Abdel Hamid Derm Atlas

Cutaneous mosaicisms
Blaschko established specific linear pattern for the distribution of lesions. ”S” shaped on the lateral &
anterior aspects of the trunk, Linear streaks on the extremities & “V” shaped on the central back
However, the line pattern on the cephalic or cervical regions appeared in hour glass shape ,
converging at the nasal root with perpendicular intersections on cervical areas of the face, spiral
intersections on scalp & V shaped in the cervical region
Classic patterns of cutaneous mosiacism
In 1993 , Happle ( Arch. Derm. 129: 146O, 1993) described several forms of segmental
manifestations of cutaneous diseases. These forma include the Blaschko lines, in
additions to four others.( Molho Pessach et al. : Clin Dermat :29, 2O5 : 2O11 ;Goldberg & Sprecher Clin
Dermat. 29: 498, 2O11 ; Siegel Advances Dermat .24: 223, 2OO8)
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A. somatic b. gonosomal c. germline
Recognizable pattern of somatic mutations in the
skin which includes: d. narrow lines of Blaschko
e. broad line of blaschko
F. chekerboard pattern
Nature reviews of genetics 14: 3O7, 2O13
Classic patterns of cutaneous mosiacism
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Type 1: Blaschko lines: This pattern is featured in a wide variety of congenital &
acquired diseases & can further be divided into two types 1a, & 1b
Type 1a :Blashko lines , narrow bands: @ typically seen in incontentias pigmenti @
Hypomelanosis of Ito.
Type 1b: Blaschko lines, broad bands:@ McCune- Albright syndrome
Type 2: the chekerboard pattern: @ Symmetrical nevus spilus @X- linked
generalized hypertrichosis, @ Becker nevus @ Cafe0au0 lait spots @ Port wine
stain @ Cutis marmorata @ Telangiactasia congenita @ Human chimeras with two
originally different ancestors can also present pigmentary disorders in this pattern.
Type 3: the phylloid pattern: It is characterized by “ leaf like” appearance in the
pigmentary disturbance. The phylloid hypomelanosis is the classic example of this
pattern. It is due to chromosome 13 trisomy or tetrasomy mosaicism. It can also
manifest with hyperpigmentation.
Type 4: Patchy pattern without midline seperation: e.g. Giant congenital melanocytic
nevus.
Type 5: Laterlization pattern: Involvement of one hemibody with sharply midline
demarcation due to abrupt interruption of lesions in this area. It is unique to CHILD
syndrome (congenital hemidysplasia + ichthysiform erythroderma + limb defect)
Cutaneous moscaicism
Epidermal nevus along Blaschko lines
X- linked incontentia pigmenti
Blaschko lines, narrow bands ( Type 1a)
Hypomelanosis of Ito
Linear hypopigmentation along the Blaschko lines
McCune- Albright syndrome
It is a genetic disorder of bones ( polyostotic fibrous dysplasia). Unilateral café-au- lait spots in the form of broad bands
of Blaschko lines (type 1b) & endocrine hyperfunction as precocious puberty
McCune –Albright syndrome (Type 1b)
Verrucous epidermal nevus
A. Brown verrucous plaques following Blaschko lines
B. Brown papules & plaques along the Blaschko lines
Verrucous epidermal nevus
Accentuation of hyperkeratosis in flexural areas
Association of lentiginous mosiacism & congenital cataract
Pigmented macules in the right arm & right side of abdomen .
Checker- board pattern .On shoulders in segmental pattern & on
the face & cheek Europ J. Dermat : 16: 36O , 2OO6
Giant congenital melanocytic nevus (Type 4)
Plaque pattern, crossing the dorsal & ventral midlines
CHILD syndrome (Type 5)
Congenital hemidysplasia + ichthysiform erythroderma + limb defect
Genetic mosaicism
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Mosaicism denotes the presence of two populations of cells with different genotypes
of an individual who has developed from a single fertilized egg .
Mutations can be divided into:
I. Gene mutation:
@ Base substitution @ Base insertion @ Base deletions The last two cause frame
shift
II. Chromosomal mutation:
A. Change in chromosome structure:
@ Chromosome deletion @ Chromosome duplication @ Chromosome insertion @
Chromosome translocation
B. Changes in chromosome number: Non disjunction ( Trisomy21 , Down’s
syndrome; Klinefelter’s syndrome 47, YXX ; Turner’s syndrome, 45, X. The
phenotype associated with mosaicism depend on the mosaic cell population.
Mosaicism has important consequence with respect to human disease,& it also result
in variations among human at the molecular level, even among identical twins.
This study is of help for understanding the behavior of genetic diseases
which will help, in the future, in gene therapy for managing these
diseases.
Non disjunction after conception
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Chromosomal mosaicism
Embryology of mosaicism patterns
When a cell undergoes a de novo post mitotic mutation during embryonic development, the resulting embryo will thus carry two genetically
distinct population. The mutated cells will express two different genetically distinct types of populations (somatic Mosaicism). It will be divided
into @ non fatal autosomal dominant diseases, @ Fatal autosomal diseases & @ Inflammatory polygenic diseases
Genetic moasicism ( somatic)
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A. Mosaicism in non fatal autosomal dominant diseases:
Type 1 segmental moasicism:
@ It is a post zygotic mutation in one of the alleles of the gene. It is not inherited except when the
mutation affects the gonads. Examples: epidermolytic hyperkeratosis, type 1 neurofibromatosis,
Darier’s disease, tuberous sclerosus, basal cell nevus syndrome, multiple syringoma ,
pachonychia congenita.
Type 2 segmental mosacism:
Mutation of one alleles of the gene during embryonic development. Therefore, there is earlier
onset of the disease & worst presentation .Examples epidermolytic hyperkeratosis, type 1
neurofibromatosis, cutaneous leiomyotosis, multiple syringomas, Darier’s disease, BuschkeOlendrof syndrome, Haily & Haily disease, disseminated superficial actinic porokeratosis
B. Mosaicism in fatal autosomal diseases:
Mutation occurs in the zygote which would be fatal to the organism
C. Mosaicism in inflammatory polygenic diseases: It is polygenic & not monogenic as type 2
segmental mosaicism. It is segmental involvment due to loss of heterogenicity. Examples:
psoriasis, lichen planus, atopic dermatitis, dermatomyositis, systemic L E. , drug eruption, vitiligo,
pemphigus vulgaris, erythema nultiformis, granuloma annulare … among others.
Hypomelanosis of Ito with hemimegalencephaly
Dermatology Online J.15:12, 23OO9
Epidermolytic hyperkeratosis
Mosaic neurofibromatosis type 1
A patient presented with several café au-laite macules (arrows) with pigmented background involving the entire right lower leg.,hip & lower back
B. patient presented with more than six café-au – laite mascules (one outlined on the left) scattered all over the body & small neurofibromas
(astriks) located on the right hand within asn overlynig café 0au- laite macule ( outlined on the right)
Am. J. Human Genetics 81: 243, 2OO7
Mosaicism for ATP2A2 mutations causes segmental Darier’s disease
J. Invetigative Derm. 115 :1144, 2OOO
Neurofibromatois genarlisita
Segmental vitiligo
Focal dermal hypoplasia ( Goltz syndrome)
Segmental Gali-Gali disease due to mutation of K5
High brown erythematous macules with fine scales on the left thigh
J. Investigative Dermatology 132: 21OO, 2O12
The above photo: Mosiacsm in Herltz junctional epidermolysis bullosa. There
are several areas of skin which are clinically normal & do not blisters
The lower photo: mosacism in dystrophic epidermolysis bullosa
Erytherma multiformis associated with metastatic breast
cancer
Ind J Dermat 58:: 485, 2O13
Porokeratosis
Epidermal nevus
Becker’s nevus syndrome
An Bras Dermat 85 no. 5 , 2O1O
Lichen striatus with Blaschko linearity
Linear atrophoderma of Moulin
Dermat Online J. 16 no.2, 2O1O
Linear psoriasis
Ind Derm Online J. 3: 71, 2O12
Chimera
An individual that developed from two distinctly germ lines e.g where two
embryos are fused in the womb. Scientists have developed a “geep” chimera
by mixing sheep & goat embryos, it has goat like legs & sheep like torso
Human chimera (pictures)
Mosaicism in cats
Mosaicsim in animals