Genetic DiseaseGenetic Disease

By: Jean LiuBy: Jean LiuID: 08301016041ID: 08301016041

General FactsGeneral Facts

Caused by an abnormality in an individual’s Caused by an abnormality in an individual’s genomegenome

Can also be caused by environmental factorsCan also be caused by environmental factors

The abnormality can range from minuscule The abnormality can range from minuscule to majorto major

Point mutation (P) – insertion/deletion entirely Point mutation (P) – insertion/deletion entirely inside one geneinside one gene

Deletion (D) – removal of a gene or genesDeletion (D) – removal of a gene or genes

C – whole chromosome extra, missing or bothC – whole chromosome extra, missing or both

Trinucleotide repeat disorder (T) – gene is Trinucleotide repeat disorder (T) – gene is extended in lengthextended in length

Very rare inherited skin disorderVery rare inherited skin disorder

A person is highly sensitive to the sunlight (photosensitive)A person is highly sensitive to the sunlight (photosensitive)

Autosomal recessive genetic disorderAutosomal recessive genetic disorder

DNA repair – ability of repair damage caused by ultraviolet DNA repair – ability of repair damage caused by ultraviolet (UV) light(UV) light

Six times more common in Japanese people than in other groupsSix times more common in Japanese people than in other groups

Around 1 in 40,000Around 1 in 40,000

Equal numbers of male and female patientsEqual numbers of male and female patients

Less than 40% of individuals with XP survive beyond age 20 Less than 40% of individuals with XP survive beyond age 20 yearsyears

Those with milder disease may survive beyond middle ageThose with milder disease may survive beyond middle age

Xeroderma PigmentosumXeroderma PigmentosumWhat Is It ?What Is It ?

* Malignancy – medical condition that * Malignancy – medical condition that can progress, can progress, potentially result in potentially result in death; eg: tumorsdeath; eg: tumors

Xeroderma PigmentosumXeroderma PigmentosumTypesTypes

Genetic ConditionGenetic ConditionCan be passed from Can be passed from generation to generation to generation in generation in

Autosomal recessive Autosomal recessive inheritance patterinheritance patter

Mutation must be Mutation must be present in both copies present in both copies of the geneof the geneCarrier – one copy of Carrier – one copy of the gene mutationthe gene mutationWhen both parents are When both parents are carrier, there is a 25% carrier, there is a 25% chance that the child chance that the child will be affectedwill be affected

Xeroderma PigmentosumXeroderma PigmentosumHow is it inherited ?How is it inherited ?

SkinSkin

EyesEyes

NeurologicalNeurological

Xeroderma PigmentosumXeroderma PigmentosumSymptomsSymptoms

Xeroderma PigmentosumXeroderma PigmentosumSkin SymptomsSkin Symptoms

Severe sunburn after a short sun exposureSevere sunburn after a short sun exposureMay last for several weeks May last for several weeks

Usually happens during a child’s first exposure to Usually happens during a child’s first exposure to the sunthe sun

Development of freckles at an early ageDevelopment of freckles at an early age

Irregular dark spotsIrregular dark spots

Thin skinThin skin

Excessive dryness of the skinExcessive dryness of the skin

Premature aging of skin, lips, eyes, mouth and Premature aging of skin, lips, eyes, mouth and tonguetongue

More than 1,000 times the risk of developing skin More than 1,000 times the risk of developing skin cancercancer

Occur nearly 80% of the patientsOccur nearly 80% of the patients

Eyes are very sensitive to the sun (photophobia)Eyes are very sensitive to the sun (photophobia)

IrritatedIrritated

BloodshotBloodshot

Cloudiness of the corneaCloudiness of the cornea

Darkening of the skin of the eyelidsDarkening of the skin of the eyelids

Xeroderma PigmentosumXeroderma PigmentosumEye SymptomsEye Symptoms

Only occur in 20-30% of people Only occur in 20-30% of people with XPwith XP

Tend to get worse over timeTend to get worse over time

Hearing lossHearing loss

MicrocephalyMicrocephaly

Spastic musclesSpastic musclesStiffness or tightness of Stiffness or tightness of

the musclesthe muscles

SeizuresSeizures

Intellectual impairmentIntellectual impairment

Poor coordinationPoor coordination

Xeroderma PigmentosumXeroderma PigmentosumNeurological SymptomsNeurological Symptoms

MildMildLight brown freckles on faceLight brown freckles on face

ModerateModerateDark brown freckles on faceDark brown freckles on face

Burning on exposed parts of the bodyBurning on exposed parts of the body

PhotophobiaPhotophobia

SevereSevereSerious dark brown frecklesSerious dark brown freckles

Burning on exposed/unexposed parts of Burning on exposed/unexposed parts of the bodythe body

Cutaneous changesCutaneous changes

Ocular changesOcular changes

Xeroderma PigmentosumXeroderma PigmentosumClassificationsClassifications

Xeroderma PigmentosumXeroderma PigmentosumCauseCause

Skin tumorsSkin tumorsMost patients die of Most patients die of skin cancer early in skin cancer early in adulthoodadulthood

Eye tumorsEye tumors

Vitamin D deficiencyVitamin D deficiency

Some are Some are hypersensitive to X-hypersensitive to X-raysrays

Patients who smoke Patients who smoke may develop lung may develop lung cancer at a relatively cancer at a relatively young ageyoung age

Xeroderma PigmentosumXeroderma PigmentosumComplicationsComplications

TestsTestsBlood samplesBlood samplesUrine samplesUrine samplesSkin biopsySkin biopsyEye examEye exam

Clouding of the cornea – loss of transparency of Clouding of the cornea – loss of transparency of the corneathe corneaKeratitis – front part of the eye becomes inflamedKeratitis – front part of the eye becomes inflamedLid tumorsLid tumorsBlepharitis – inflammation of the eyelash folliclesBlepharitis – inflammation of the eyelash follicles

Fibroblast cultureFibroblast cultureDNA repairDNA repairUV sensitivityUV sensitivity

AminocentesisAminocentesisTest before the birth of the child - take sample Test before the birth of the child - take sample of fluid from the sac around the babyof fluid from the sac around the baby

Xeroderma PigmentosumXeroderma PigmentosumDiagnosisDiagnosis

There is no cure for XP so farThere is no cure for XP so far

Many management methods to cope Many management methods to cope with the problemswith the problems

Xeroderma PigmentosumXeroderma PigmentosumTreatmentTreatment

PhysicallyPhysicallyReducing exposure to the Reducing exposure to the sunsun

Sun glassesSun glassesClothing (long sleeves, Clothing (long sleeves, long pants, gloves)long pants, gloves)Optical filtrationOptical filtrationLots and lots of Lots and lots of sunscreenssunscreens

ChemicallyChemicallyReducing the number of Reducing the number of keratoses with keratoses with IsotretinoinIsotretinoin

HousingHousingHalogen lampsHalogen lamps

Xeroderma PigmentosumXeroderma PigmentosumManagementManagement

* Keratoses – keratin (on the skin)

Two partsTwo partsHeadgearHeadgear

Protect head and Protect head and faceface

SuitSuitCovering the rest Covering the rest of the bodyof the body

Filtering 100% UV-Filtering 100% UV-lightlight

Xeroderma PigmentosumXeroderma PigmentosumManagementManagement

Focuses more on future problemsFocuses more on future problems

Frequent check-ups and examinationsFrequent check-ups and examinationsSkin specialist (dermatologist)Skin specialist (dermatologist)

Eye specialist (ophthalmologist)Eye specialist (ophthalmologist)

Xeroderma PigmentosumXeroderma PigmentosumPreventionPrevention

Wan Lao Yang – the Wan Lao Yang – the girl who lives in the girl who lives in the darkdark

An XP patientAn XP patient

Her facial tumors Her facial tumors made it impossible made it impossible for her to wear the for her to wear the UV protective suitUV protective suit

The cancer had The cancer had spread to her lungsspread to her lungs

Died on June 2006Died on June 2006

Xeroderma PigmentosumXeroderma PigmentosumA Case In ChinaA Case In China

Genetic DiseaseGenetic Disease

By: Jean LiuBy: Jean LiuID: 08301016041ID: 08301016041