GENETICS IN DERMATOLOGY
GENETICS (Gk: Genesis – Origin)
The branch of biology that deals with heredity, especially the mechanisms of hereditary transmission and the variation of inherited characteristics among similar or related organisms
HUMAN GENOME ORG
GENETICS : PRINCIPLES
• GENE (Grk ‘Genea’ – Descent) Basic Unit of Heredity Info to Build / Maintain Cells & Transfer traits to Offspring
Sequence of DNA bases
GENETICS : PRINCIPLES• CHROMOSOME Storage Units of Genes
Females 23 Homologous Pairs 22 AUTO + 01 ALLO each Somatic Cell 22 Homologous + 01 Heterologous pair - Males
GENE LOCUS
Genes arranged inspecific location onChromosome - LOCI
GENETICS : PRINCIPLES
ALLELE - Alternative genes at Single Locus
HETEROZYGOUS (Aa) HOMOZYGOUS (AA)
GENETICS : PRINCIPLES
GENOTYPE - Inherited Instructions within an Organism’s genetic code; Blueprint, Constant, Str / Func
PHENOTYPE - Observable traits like Morphology, Properties, Changes with Environmental Influence &
Developmental Conditions
Differ due to
PENETRANCE
Proportion of individuals who carry a disease causing mutated gene and exhibit the clinical phenotype over a defined period.
Failure to exhibit Phenotype even though they carry the affected gene; this condition is termed as REDUCED / INCOMPLETE PENETRANCE
AD Dis e.g. TUBEROUS SCLEROSIS
GENETICS : PRINCIPLES
DOMINANT ALLELES - Phenotypic Expression with Heterozygous Allele
RECESSIVE ALLELES - Phenotypic Expression only with Homozygous Alleles
GENETIC HETEROGENICITY
• EXACT CLINICAL PHENOTYPES due to several Gene Mutations
• LAMELLAR ICHTHYOSIS
Mut in TGM-1 / ABCA12 / CYP4F22
CLINICAL HETEROGENICITY
• Mut in Single-Gene-Locus Several Phenotypic Variants
E.g. Mut in Connexin 26 causing Vohwinkel Syn Keratitis-ichthyosis-deafness (KID) Syn
MOSAICISM
Presence in an individual of 2 (or more) genetically distinct cell populations derived from the same homozygous zygote.
Functional Mosaicism - Normal Human Female with 46, XX (One X Chr inactivated during Embryogenesis by Lyonization into Barr Body)
MITOSIS
Cellular Growth / Repair / Asexual Reproduction
1 Parent Cell 2 Diploid Cells (2n)
Identical Daughter Cells
MEIOSIS
Sexual Reproduction / Production of Gametes
1 Parent Cell 4 Haploid Cells (n)
Daughter Cells different from Parent Cells
Chromosomal Cross-Over
CELL DIVISION
NOSOLOGY (Gk ; Nosos + Logos)
•FAMILIAL - ‘Clustering’ Higher Prevalence in relatives than population
eg HAILEY-HAILEY DIS
•CONGENITAL - present since Birth +/- Genetic -Developmental Defects- Infectious (RUBELLA) Insult (AMNIOTIC BAND SYN)
NOSOLOGY
POLYGENIC
Multifactorial
Multiple Genes + Environmental Influences
ATOPIC DERMATITIS PSORIASIS VULGARIS
GENODERMATOSES
• INHERITED DISORDERS
Alteration in Function of SINGLE GENE
Typical Inheritance Patterns AD / AR / XD / XR
AUTOSOMAL DOMINANTBoth Sexes
HeterozygousFor Abn Allele‘AFFECTED’
50% Transmission (Average)Positive Family History
AUTOSOMAL DOMINANT
Acute intermittent porphyria PBG
Ichthyosis (some forms) FILAGGRIN
Neurofibromatosis NF1
Tuberous sclerosis TSC1/2
Hereditary haemorrhagic telangiectasia ENG
AUTOSOMAL RECESSIVEBoth Sexes
Homogenous forAbn Allele is‘AFFECTED’
25% Transmission
No Family History (Carriers)
AR
Consanguinous Marriages / Ethnic Groups(Isolated Allele Groups)
Increased Risk of Carrier Parents
Risk of Affected Individual (25%)
AUTOSOMAL RECESSIVE (AR)
Epidermolysis bullosa DSP
Severe Ichthyosis ABCA12
Acrodermatitis enteropathica SLC39A4
Phenylketonuria PAH
Xeroderma pigmentosum XPA/B/C/D
X-LINKED DOMINANTHemizygous MaleHeterozygous Female
Affected Male to Daughters
Affected Female To 50% eachSon/Daughter
X-LINKED DOMINANT (XD)
Incontinentia pigmenti NEMO
Oro-facial-digital syndrome OFD1
X-LINKED RECESSIVEUsually Males
Atavistic
No Father to Son
Carrier Mother : SONOne Daughter Carrier
X-LINKED RECESSIVE (XR)
Anhidrotic ectodermal dysplasia EDA
Fabry’s disease A-GAL A
Menke’s syndrome ATP7A
Ocular albinism GPR143
CHROMOSOMAL DISORDERS
DEFECTS :
Change in no of Chr (ANEUPLOIDY)
Monosomy - TURNER’S SYN
Trisomy - DOWN’S EDWARD’S PATAU’S
CHROMOSOMAL DISORDERSDEFECTS :
Chr Str Rearrangement
Deletion - CRI-DU-CHAT Translocation - BURKITT’S LYMPHOMA Non-Dysjunction - KLEINFELTER’S DOWN’S
CHROMOSOMAL DISORDERS
• DEFECTS based on Chromosomes involved
AUTOSOMES SEX CHROMOSOMES
DOWN’S / EDWARD’S TURNER’S / KLEINFELTERS
PATAU’S / CRI-DU-CHAT FRAGILE-X / XXY / XXYY /CHR 4p DEL / CHR 18q DEL XXXXY
DOWN’S SYN
47, XX(XY), +21 1:700 LB ‘MONGOLIAN SYN’
DS – SYSTEMIC MANIFEST
DS – DERMAT MANIFEST
Birth - Soft, Velvety Skin 5 and 10 YO - Dry / Less Elastic15 YO – Generalized Xerosis20 YO - Patchy Lichenidication
Folliculitis Assoc with Malassezia Furfur; Responsive to ItraconazleAssoc with
DS – DERMAT MANIFEST
Fine, Hypopigmented Hair
Assoc with Alopecia Arreata
Recurrent Skin infections, Angular Cheilitis
Assoc with Onychomycosis
OTHER AUTOSOMAL DIS
EDWARD’S SYN 47,XX(XY),+18 Hypomelanosis
CRI-DU-CHAT SYN 46,XX(XY),-5p Premature Greying of Hair
LONG-ARM-DELETION-18 46,XX(XY),-18qEczema (25%)
TURNER’S SYN
45,XO 1:2500 LBs
TURNER’S SYN-MANIFEST
TURNER’S SYN-DERMAT FEATURES
• Hypoplastic Nails
• Keloidal Tendency
• Melanocytic Naevi Melanoma
KLEINFELTER’S SYNDROME
• 47,XXY 1:600 LBs
• Assoc with SLE INCONTINENTIA PIGMENTI LIVEDOID VASCULITIS LEG ULCERS
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