Optimized Genetic Diseases - Ch 4 BRS Path

8/19/2019 Optimized Genetic Diseases - Ch 4 BRS Path

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Genetic diseasesgraphics to accompany chap 4 of BRS path 2nd edition

note: some diseases omitted because there were no graphics available or the diseases were obvious (Cystic fibrosis)

Suhas Radharishna !"##"$%


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Autosomal Chromosome D/o 1:

Down syndrome

&arge forehead'broad nasal

bridge' widespaced eyes'large tongue'small low setears' picanthalfolds

Brushfield spots

Simian* crease' curved!th finger' wide spacebetween first andsecond toes

Congenital heart d+ in2$, of patients' -&&'susceptibility toinfection' -l+heimerslie disease

.risomy 2#' or /arental0eiotic translocation btchromosome 2# and

another chromosomet(#412#1)

http://images.google.com/imgres?imgurl=www.tl.infi.net/~jwheaton/pictures/ann200.gif&imgrefurl=http://www.tl.infi.net/~jwheaton/dsnet.html&h=319&w=224&prev=/images%3Fq%3Ddown%2Bsyndrome%26svnum%3D10%26hl%3Den%26lr%3D%26ie%3DUTF-8%26oe%3DUTF-8http://images.google.com/imgres?imgurl=www.tl.infi.net/~jwheaton/pictures/ann200.gif&imgrefurl=http://www.tl.infi.net/~jwheaton/dsnet.html&h=319&w=224&prev=/images%3Fq%3Ddown%2Bsyndrome%26svnum%3D10%26hl%3Den%26lr%3D%26ie%3DUTF-8%26oe%3DUTF-8


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Autosomal # 2: Cri du Chat

picanthal folds'Round face'3ypertelorism(wide set eyes)'&ow set ears

Cat lie cry

Severe mental retardation

&ow birth weight

0icrocephaly

Chromosome !p deletion


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Autosomal # 3: DiGeorge Syndrome

Cardiac (aortic arch)-bnormal facies.hymic hypoplasia(Recurrent viral andfungal infections)

Cleft palate3ypocalcemia(hypo/.3 56 tetany)

0alformed ear'mandible

0icrodeletion of 221##


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Autosome 4: Edwards syndrome

7verlapping fingers

/rominent occiput

0icrognathia

&ow set ears

Congenital heart disease

Rocerbottom feet are a feature of/atau8s and dward8s syndromes anddesribes feet shaped lie the runnerof a rocing chair' ie gently curvedupwards at both ends9

.risomy #


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Autosome 5: atau syndrome

0ental retardation0icrocephaly

Cleft lip and palate

/olydactyly

Rocer bottomfeet

Congenitalheart

disease

.risomy #%


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Se! "hromosome 1: line$elter

3ypogonadism

.all (fusion of epiphyses delayed)

;ynocomastia

4


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Se! Chromosome 3: %urner

Strea ovary

@ebbed nec' short' shield chest wAwide spaced nipples' wide carrying

angle of arms' &- of nec and andetremities

Coarctation of aorta

4! ='$

/rimary amenorrhea


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Anti"i&ation diseases

Dragile =: macroorchidism' mental retardation

3untingtons

0yotonic Eystrophy


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'm&rinting 1: rader (illi

Fncontrolledappetite "6 obesity

3ypogonadism

0ental retardation

Behavior problems

3ypotonia

Eel (#!)(1##'1#%) in the father

http://images.google.com/imgres?imgurl=www.geocities.com/kbrorman/victor2.gif&imgrefurl=http://www.geocities.com/kbrorman/Prader-Willi_Syndrome.html.html&h=204&w=182&prev=/images%3Fq%3DPrader%2Bwilli%26svnum%3D10%26hl%3Den%26lr%3D%26ie%3DUTF-8%26oe%3DUTF-8


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'm&rinting 2: Angelman Syndrome

0ental retardation

Sei+ures

-taia

Gnappropriate laughter

Eel (#!)(1##1#%) in the mother

http://www.users.bigpond.com/websterpaul/k&p2.jpg


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Autosomal Dominant 3:

)sler (e*er +endu Syndrome

,ereditary ,emorrhagi"

%elangie"tasia

.elangiectasias of mouth and sin'3emorrhage from them9


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-ar$an Syndrome

ctopia lentis (dislocation of lens)

arachnodactyly

-neurysm of /roimal -ortaA-ortic dissectionA0itral Halve /rolapse

@ingspan 6 heightEeficiency of Dibrillin

http://www.medstudents.com.br/original/revisao/marfan/marfan.jpg


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Autosomal Dominant .:

euro$i*romatosis

0ultiple neurofibromas

CafI au lait spots

&isch nodules: iris hamartomas

@ilms tumor/heochromocytoma

&euemiaRhabdomyosarcoma

ScoliosisBone cysts

0utations in JD# gene' a tumor suppressor

that normally ras;./ 56 ras;E/


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%u*erous S"lerosis

-denoma sebaceum;lial nodulesEistorted neurons in corteSei+ures0ental Retardation

Rhabdomyoma of heart

Renal -ngiomyolipomas:0alformed blood vessels' smooth muscle' and fat

Subependymal giantcell astrocytoma ispathognomonic

.S#A.S2 gene

-sh leaf spots on trun

/ancreatic cysts


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Autosomal Dominant :

on ,i&&el indau Disease

Renal cell carcinoma

3emangioblastomaACavernous hemangioma of:CerebellumBrainstemRetina

Cysts of &iver' idney'/ancreas' other organs

Eeletion in chromosome %


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ysosomal 1: %ay Sa"hs

Eeath before 4 years old usually

Cherry red spot on macula

Blindness

CJS degeneration0entalAmotor deterioration

n+yme Eeficiency: 3eosaminidase -

-ccumulation: ;m2 ganglioside


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ysosomal 2: Gau"her disease

@rinled tissue paper cytoplasm;auchers in spleen' &J' liver'bone marrow (R system)

Demoral head Along bone erosion0ild anemia

.ype GG (infantile) CJS involvement'Eeath before # year old

.ype GGG (?uvenile) also has CJS complications

n+yme Eeficiency: ;lucocerebrosidase A B"E glucosidase-ccumulation: ;lucocerebroside A ;lucosylceramide

Jote: the first is from BRS the second from Kban' both seemed to be used by emedicine


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ysosomal 3: iemanni" Disease

Doamy histiocytes in

liver' spleen' &J' sin

3epatosplenomegaly

!$, of pts : cherry redspot

Dever' neuro deterioration

-nemia

Eeath by age %

n+yme deficiency: Sphingomyelinase

-ccumulation: Sphingomyelin


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ysosomal 4: ,urler syndrome

;argoyle"lie* facies(terrible name)

Stubby fingers

Corneal clouding

/rogressive mental retardation

Eeath by age #$

Ewarfism

n+yme deficiency: alpha"& iduronidase

-ccumulation: 3eparan sulfate' dermatan sulfate


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Gly"ogen Storage 1: 6on Giere disease

-ccumulation of glycogen in liver and idney 56 hepatomegaly

3ypoglycemia

n+yme deficiency: ;lucose L phosphatase-ccumulation: ;lycogen


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Gly"ogen storage 2: om&e disease

cardiomegaly

Eeath before age % of cardiorespiratory failure

0uscle hypotonia

Splenomegaly

Gntractable 3ypoglycemian+yme deficiency: alpha"#'4 glucosidase-ccumulation: ;lycogen


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Gly"ogen Storage 3: Cori Disease

Stunted growth

;lycogen in liver "6 3epatomegaly

hypoglycemia

;lycogen accum in heart

;lycogen in seletal muscle

n+yme deficiency: -mylo"#'L"glucosidase-ccumulation: ;lycogen

G S S


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Gly"ogen Storage 4: -"Ardle Syndrome

0uscle cramps and weaness after eercise

n+yme deficiency: 0uscle phosphorylase-ccumulation: ;lycogen

C * h d t 1 Cl i l t i


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Car*ohydrate 1: Classi" gala"tosemia

Cirrhosis

Dailure to thrive

0ental retardation

n+yme deficiency: ;alactose"#"phopshate uridyl transferase-ccumulation: ;alactose "#"/

A i A id 1 7


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Amino A"id 1: 7

/rogressive mentaldeterioration

Sei+ures

3yperactivity

Jeuro problems

0ustyAmousy body odor

Eecreasedpigmentation of hair'

eyes' sin

n+yme deficiency: /henylalanine hydroylase-ccumulation: /henylalanine and its degradation products phenylpyruvic acid and phenylacetic acid

A i A id 2 Al t i


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Amino A"id 2: Ala&tonuria

7chronosis M dar pigmentation of fibroustissues and cartilage

Can affect the ?oints and the heart

EarABlac urine

n+yme deficiency: 3omogentisic oidase-ccumulation: 3omogentisic acid


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Amino A"id 3: -a&le Syru&

7rine Disease

Frine smells lie maple syrup

Can lead to neonatal death if untreated

ny+me deficiency: branched chain alpha"eto acid dehydrogenase constituent proteins

8 li d 1 , t S d


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8 lined 1: ,unter Syndrome

3epatosplenomegaly

0icrognathia

Retinal degeneration

0ild mental retardation

Noint stiffness

Cardiac lesions

n+yme deficiency: &"Gduronosulfate sulfatase-ccumulation: 3eparan sulfate' dermatan sulfate

8 li d 2 9 * di


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8 lined 2: 9a*ry disease

-ngioeratomas over lower trun

Eeath from Renal failure

Debrile episodesCerebrovascular episodes

Burning pain inthe etremities

Cardiovascular involvement*

n+yme deficiency: alpha";alactosidase --ccumulation: Ceramide triheoside

8 li d 3 , hili A


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8 lined 3: ,emo&hilia A

9a"tor ''' de$i"ien"y;

3emarthrosesAdisability

7ral bleeds

3ematuria

8 lined 4: es"h yhan syndrome


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8 lined 4: es"h yhan syndrome

;out

0ental retardation

Choreoathetosis

Spasticity

0issing finger from self mutilation (biting)

-ggressive behavior

n+yme deficiency: 3;/R.-ccumulation: Fric -cid

Se!ual Di$$erentiation


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Se!ual Di$$erentiation

HERMAPHRODITISM

TRUE HERMAPHRODITEGt is an individual' who has both ovarian and testicular tissue' which may be in the form of an ovary on one side and atestis on the other' or in the form of a combined form' an ovotestis9 .his type is not seen often by the clinician9 @hen it

occurs' it is usually a patient with the 4L'== aryotype' with fairly normal ovarian tissue but with degenerate testiculartissue9 Demale genital ducts are usually present' and may be accompanied by the male genital ducts' which if presentwould be on the same side as that of the mied gonad which contained large amounts of testicular tissue9.he aetiology ofthis condition is unnown at the present time9 -mbiguous genitalia9

PSEUDOHERMAPHRODITEGt is of two types9 0ale and female pseudohermaphrodites9

Male pseudohermaphrodite- common entity that belongs to this group is the .esticular Demini+ation Syndrome or the -ndrogen GnsensitivitySyndrome9 .he chromosome complement is 4L'=>' the gonads are testes but the genital ducts and the eternal genitaliaare female9 .he testes do not undergo normal descent and remain abdominal' in the inguinal canal or lodged in the labiama?ora9 .he testes function in producing testosterone and mullerian inhibiting a!tor9 Conse1uently' the uterine tubes'the uterus and the upper part of the vagina fail to develop' they being derivatives of the mullerian or paramesonephricducts9.he lac of testosterone sensitivity due to the absence of receptors or the absence of the testosterone receptor protein attarget tissues which bind testosterone and dihydrotestosterone' lead to development of the female body habitus9 .he lacof testosterone activity also leads to the failure of the development of mesonephric derivatives which are testosteronedependent9 .he clinical features are' a emale phenotype "ith a #$%&' (aryotype% primary amenorrhoea% pau!ityo pubi! and other body hair% blind vaginal pou!h and intrabdominal testes97ther male pseudohermaphrodites have various en+yme defects in the many stages of androgen production9

)emale pseudohermaphrodite3ere the individual has a 4L'== chromosome complement' a deinite emale body habitus% emale gonads andgenital du!ts% but the e*ternal genitalia are ambiguous9 .here may be many causes of this condition9 0aternaleposure to virili+ing drugs or rarely the mother having a virili+ing tumour or virili+ing endocrine disorder may produce afemale pseudohermaphrodite9 .he most common one is the adrenogenital syndrome caused by congenital adrenalhyperplasia9 Fsually there is a congenital lac of certain adrenal cortical en+ymes of the foetal adrenal gland' needed forsteroid metabolism9 .his results in an accumilation of androgens in the foetus9 .he androgenic stimulation usually occursafter the gonads and genital ducts have passed a critical period' but while the developing eternal gonads are stillsensitive9

Optimized Genetic Diseases - Ch 4 BRS Path

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