edwards syndrome - SGA - VSD +/- valve dysplasia - short sternum - overriding fingers - 'rocker bottom feet' - multiple choroid plexus cysts on CrUSS

Genetics Flashcards by Catherine Hunter

Frame-shift mutation

Type of insertion mutation
1 or more bases inserted, changing the way the DNA is read

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Deletion mutation

deletion of a nucleotide, can lead to a non-functional protein

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Missense mutation

alteration of a nucloetide sequence that converts one codon for an aminoa cid into a codon for a second amino acid

can lead to pathogenic variant or unknown significance

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Nonsense mutation

changes a triplet coding for an amino acid into a termination codon, leading to a non-functional protein

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Point mutation

Single nucleotide change ina DNA molecule

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What can array CGH not detect

balanced chromosomal rearrangements

cant distinguish between unbalanced chromosomal rearrangements caused by different mechanisms

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CHD associated with turner’s syndrome

CoA and VSD

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Trisomy 13 features

patau syndrome

midline defects
- cleft palate
- ASD or VSD
- fused kidneys
- holoprosencephaly
- microphthalmia

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Trisomy 18 features

edwards syndrome

SGA
VSD +/- valve dysplasia
short sternum
overriding fingers
‘rocker bottom feet’
multiple choroid plexus cysts on CrUSS

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Physiology of how DiGeorge syndrome affects embryology

the deletion causes a reduction in T-box transcription factor 1 (TBX1) which disrupts the development of the 3rd and 4th pharyngeal arches

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williams syndrome genetic defect

microdeletion on chromosome 7q11 - encompasses the elastin gene

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presentation williams syndrome

cardiac - SUPRAvalvular aortic stenosis often with peripheral pulmonary branch stenosis

periorbital fullness
wide mouth & full lips
flat nasal bridge
mental retardation
hypercalcaemia
overfriendliness/short attention span/anxiety

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what is an imprinting disorder

inherited genes are expressed only from a copy inherited by one parent

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causes of imprinting disorder

methylation defect
- switches off genes that are normally active or switching on genes that are normally silenced

uniparental disomy
- inheritance of borth copies of a chromosome from only 1 parent

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examples of imprinting disorders

prader willi

angelman

beckwith-widemann syndrome

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imprinting defects causing prader-willi syndrome

Essentially expression of only maternal copy

MATERNAL uniparental disomy at chromosome 15q11 (SNRPN Gene mutation)
Large deletions of the PATERNAL copy of 15q11
Methylation defects

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Presentation of prader-willi syndrome

Hypotonia
Poor feeding
Overeating&raquo_space; obesity
Hypogonadotrophic hypogonadism
Small hands and feet
Temper tantrums
High pain tolerance
Almond shaped eyes
Thin upper lip

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Imprinting defects causing angelman syndrome

Essentially expression of only paternal copy

PATERNAL uniparental disomy at chromosome 15q11
Large deletions of the MATERNAL copy of 15q11
Loss of function mutations on the maternal allele of UBE3A

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Presentation of angelman syndrome

developmental delay
ataxia
happy disposition phenotype
wide mouth
seizures

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cause of BWS

disruption of the imprinted region on chromosome 11p15

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tumour that BWS patients at higher risk of and what monitoring is done

wilms tumour

abdo US every 3m until age 7

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marfans genetic defect

missense mutation in the FBN1 gene on chromosome 15q - encodes for fibrillin

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neurofibromatosis type 1 genetic defect

mutation in NF1 gene on 17q11.2

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pathophysiology of neurofibromatosis

NF1 gene encodes for neurofibromin - a tumour suppressor protein (RAS-GAP)

Neurofibromin most common in neurons, glial cells and schwann cells

NF1 gene defect leads to RAS hyperactivation&raquo_space; activation of pro malignancy pathways

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Criteria for NF1 diagnosis

2 or more of ... - 6x cafe au lait macules - 2x or more neurofibromas or 1x plexiform neurofibroma - axillary or inguinal freckling - 2 or more lisch nodules - distinctive bony lesion - 1st degree relative with NF1

what are lisch nodules

raised tan coloured haematomas in the iris

diagnostic criteria for NF2

1x major or 2x minor Major - unilateral vestibular schwannnoma % 1st deg relative with NF1 - bilateral vestibular schwannomas Minor - meningioma - schwannoma - ependyoma - glioma - cataract

mutations for tuberose sclerosis

point mutations on TSC1 - chromosome 9 - encodes for hamatin TSC2 - chromosome 16 - encodes for tuberin

pathological consequence of TSC1 or 2 mutations

dysregulation of mTOR (mamamalian target of rapamycin)

achondroplasia mutation

AD mutation in the fibrobast growth factor receptor 3 (FGFR3) on chromosome 4

diagnostic achondroplasia features at birth

short metacarpals and phalanges short ribs with cupped anterior end large skull with narrow foramen magnum

cause of myotonic dystrophy

monoalleic triplet repeat expansion in DMPK gene (type 1) or CNBP gene (type 2)

associated features of myotonic dystrophy (apart from muscle weakness)

cataracts & diabetes

cause of fragile x

full expansion repeats in the CGG triplet repeat in the FMR1 gene on Chromosome Xq27.3

Inheritance of alagille syndrome

genetic defect in alagille syndrome

defect in the JAG1 gene on chromosome 20

presentation of alagille syndrome

butterfly vertebrae cholestasis facial - broad forehead, hypertelorism, small pointed chin anterior segment abnormalities - posterior embryotoxin

mutation in CF

CFTR gene on chromosome 7

inheritance of DMD

x linked recessive

inheritance of Rett syndrome

x linked dominant

genetic defect of rett syndrome

loss of function mutation in MECP2 gene on X chromosome

presentation of rett syndrome

exclusively females apparently normal development then regression of skills and deceleration of head growth 6-18m midline hand movements - shaking, inability to hold things

genetic defect in incontentia pigmenti

mutation in the NEMO gene on Xq28

inheritance of incontentia pigmenti

x linked dominant

presentation of incontentia pigmenti

affected male pregnancies most liley will miscarry cropped circumferential blisterning lesions on the trunk with linear distribution on the limbs lesions regress by late childhood and leave atrophic streaky areas of pigmentation

inheritance of holt-oram syndrome

genetic defect in holt oram syndrome

TBX5 gene mutation on chromosome 12

presentation holt-oram syndrome

hypoplastic thumbs ASD absent radii

CHARGE syndrome

coloboma heart disease atresia (choanal) retardation of growth genitourinary abnormalities ear anomalies

presentation of pierre robin

3 classic features - cleft palate - glossoptosis - micrognathia

inheritance of treacher collins

genetic defect in treacher collins

TCOF1 gene mutation on chromosome 5q32

pathophysiology of treacher collins

failure of neural crest cells to develop into the first pharyngeal arch in 4th week of pregnancy

presentation of treacher collins

micrognathia malar hypoplasia ear malformations down slanting eyes conductive deafness lower eyelid coloboma

associated ocular manifestion of familial adenomatous polpyosis

congenital hypertrophy of the retinal pigment epithelium

genetic defect in hereditary spherocytosis

ANK1 gene mutation

genetic defect in cri du chat

deletion of the 'p' arm

inheritance of tay sachs

cause of tay sach's disease

mutation in the hexosamindase subunit alpha (HEXA) gene on chromosomal 15

pathophysiology of tay sachs

mutation > diminished levels of hexasamindase A enzyme > failure ot breakdown GM2-ganglioside > accumulation within neurones of the brain and spinal cord

inheritance of pendred syndrome

presentation of prendred syndrome

bilateral sensorineural deafness vestibular dysfunction (bilateral dilatation of the vestibular aqeducts) goitre

Ix for pendred syndrome

MRI middle ear

inheritance of laurence-moon-biedl syndrome

presentation of laurence-moon-biedl syndrome

obesity cranial DI hypogonadism night blindness retinitis pigmentosa polydactlty tinnitus

inheritance of cockayne syndrome

presentation russell-silver syndrome

prenatal growth restriction triangular face 5th finger clinodactlyly cafe au lait spots sweatiness

inheritance of noonans syndrome

genetic defect in noonans syndrome

PTPN11 gene mutation on chromosome 12q

presentation noonans syndrome

short stature hypertelorism pulmonary stenossis hypertrophic cardiomyopathy pectus carinatum / pectus excavatum mild DD undescended testes

Genetics Flashcards

(70 cards)