Genetics

Question 1

PAX 2 gene is associated with ____

Answer 1

Renal-Coloboma syndrome

Question 2

CHD7 mutation is associated with _____

Answer 2

Charge syndrome

Question 3

ATP7B associated with _____

Answer 3

Wilson’s disease

Question 4

SERPINA 1 related to ______

Answer 4

Alpha 1 antitrypsin deficiency

Question 5

UBE3A related to ______

Answer 5

Angelman syndrome

Question 6

DHCR7 related to ____

Answer 6

Smith-Lemli-Opitz Syndrome

Question 7

Abnormal architecture of the vitreous gel is pathognomonic of _____

Answer 7

Stickler syndrome

Question 8

Usher syndrome is associated with hearing loss but also _______________

Answer 8

ataxia and retinitis pigmentosa

Question 9

Children with Pendred syndrome have a _______ associated with deafness

Answer 9

Goitre

Question 10

Features of Alport syndrome are ______, ______ and _______

Answer 10

Features of Alport syndrome are nephritis, deafness and retinitis.

Question 11

Describe the syndrome:

1 in 16,000 live births, Holoprosencephaly, cutis aplasia, midline defects, microphthalmia, coloboma, polydactyly/clenched hand

Answer 11

Trisomy 13 - Patau Syndrome

Question 12

Describe the syndrome:

1 in 8,000 live births,
Hypertonia, arthrygrpossis, Rocker-bototm feet, overlapping fingers, omphalocoele, diaphragmatic hernia, severe mental retardation

Answer 12

Trisomy 18 - Edwards Syndrome

Question 13

Describe the syndrome:

1in 2,000
Short stature, broad chest, low posterior hairline, webbed neck..

Name two other features and the most common congenital heart condition

Answer 13

Turner Syndrome - XO

Cubitus Valgus, Infertility, Wide spaced nipples

35% with CHD. Most commonly bicuspid aortic valve with early stenosis and later on aortic regurgitation

Question 14

Describe the syndrome:

1 in 1000
Tall stature, low IQ, Hypergonanadotrophic hypogonadism (small testes, infertile), gynaecomastia

Also what percentage have congenital heart disease?

Answer 14

Kleinfelters syndrome XXY

50% have CHD - ASD and PDA

Question 15

Describe the syndrome:

1 in 4000
Cardiac anomalies, hypocalcaemia, thymic aplasia

What is the most common mental health disorder?

Answer 15

22q.11 microdeletion

30 fold increased risk of schizophrenia

Question 16

Describe the syndrome:

1in 1,000-2,500
Short stature, hypertelorism, refractor errors, small upturned noses, low set posteriorly rotated ears

Answer 16

Noonan syndrome

Question 17

In Noonan’s Syndrome 70% deletion mutation in ____________

Answer 17

70% deletion mutation in RAS/Mitogen activated protein kinase signalling pathway

Question 18

Marfans syndrome is a result of ______ protein mutation in chromosome __

Answer 18

FBN1 gene mutation for Fibrillin in chromosome 15

Question 19

What ocular anomaly is noted in Marfans syndrome?

Answer 19

Ectopia Lentis

(Up and in)

Homocysteinuria also has Ectopia Lentis but down and out

Question 20

Describe the syndrome:

Has orofacial features such as frontal bossing, hypoplastic maxilla, and supernumerary teeth. The primary teeth can be overretained, and the permanent teeth remain unerupted. Supernumerary teeth are common, especially in the premolar area

Answer 20

Cleidocranial dysplasia

Question 21

Mutation in COL2A1 associated with:

Prominent joints, arthritis, hypotonia, hypermobile joints, mitral valve prolapse, hearing loss in adolescence, spine problems (scoliosis, kyphosis, platyspondyly), and ocular problems (high myopia, choroidoretinal and vitreous degeneration; retinal detachment is common during childhood)

Answer 21

Autosomal dominant condition

Stickler syndrome (30-50% of Pierre Robin sequence have this)

Question 22

15q 11-13 maternal deletion syndrome = ________

15q11-13 paternal deletion syndrome = _________

Answer 22

15q 11-13 maternal deletion syndrome = Angelman syndrome

15q11-13 paternal deletion syndrome = Prader-Willi syndrome

Question 23

_________ syndrome is a neurodevelopmental disorder characterized by severe intellectual disability, postnatal microcephaly, and a movement or balance disorder, usually in the form of gait ataxia and/or tremulous movement of limbs.

Kids often have frequent laughter or smiling; apparent happy demeanor with emotional lability; an easily excitable personality, often with hand flapping movements.

Seizures by the age of 2

Answer 23

Angelman syndrome

Question 24

Most common genetic defect for Angelman syndrome?

Answer 24

Gene deletion in 70% cases

Question 25

What is the genetic testing for Angelman syndrome?

Answer 25

Methylation studies first, followed by chromosome microarray (array comparative genomic hybridization [aCGH]). If methylation studies are positive, the next step is to determine by microarray if the patient has a class I or class II deletion. Class I more severe

Question 26

_______ syndrome is characterized by hypotonia, poor feeding in infancy with failure to thrive but increased appetite and obesity in children and adults.

Answer 26

Prader Willi Syndrome Also seen is genital hypoplasia, small hands and feets

Question 27

What are the two most common genetic defects that contribute towards Prader Willi Syndrome?

Answer 27

Deletion of paternal 15q11.2-13 – 50 to 75 percent of cases. Maternal uniparental disomy – 20 to 50 percent of cases.

Question 28

What are the most common features of PWS: - In infancy/neonate: - School age children:

Answer 28

Infancy/neonate: - Neonatal and infantile hypotonia, feeding problems during infancy, excessive weight gain after infancy, characteristic facial features, hypogonadism School age children: - hypotonia - GDD - Food seeking/obesity/always eating - premature adrenarche, but puberty delayed otherwise - Autism spectrum in 27%

Question 29

_______________ is a mitochondrial cytopathy that is characterized by Chronic Progressive External Ophthalmoplegia, retinal pigmentary changes, and heart block. Patients are typically normal at birth. Progressive ophthalmoplegia usually develops between 5 and 20 years of age, although it may occur earlier. Most cases are sporadic.

Answer 29

Kearns- Sayre syndrome Also associated with autoimmune thyroid, adrenal disease, and diabetes; and cardiac conduction defects

Question 30

mental retardation autistic behaviour macro-orchidism facial features – long face, large cupped ears, prominent square jaw Which syndrome?

Answer 30

Fragile X

Question 31

Name 4 common triple repeat disorders?

Answer 31

1) Fragile X - CGG 2) Huntington's disease - CAG 3) Fredreich's Ataxia - GAA 4) Myotonic dystrophy - CTG 5) Spinocerebellar ataxia - CAG

Question 32

PTPN11 or RAS-mitogen activated protein kinase (MAPK) is associated with which syndrome?

Answer 32

Noonan syndrome

Question 33

Short palpebral fissues, long, smooth philtrum, thin vermillon border, maxillary hypoplasia and ptosis....

Answer 33

Fetal alcohol syndrome

Question 34

Whats the syndrome? - Low serum copper and ceruloplasmin levels, as well as a defect in intestinal copper absorption and transport. - Symptoms begin in the first few months of life and include hypothermia, hypotonia, and generalized myoclonic seizures. T - Chubby, rosy cheeks and kinky, colorless, friable hair. Microscopic examination of the hair shows several abnormalities, including trichorrhexis nodosa (fractures along the hair shaft) and pili torti (twisted hair)

Answer 34

Menke disease X-linked recessive trait. The Menkes gene, ATP7A, on Xq21.1,

Question 35

Alongside cerebral calcifications and a family history; what lab markers on CSF might you see for Aicardi Goutieres syndrome?

Answer 35

normal metabolic and infective screening. An increase in the number of white cells (particularly lymphocytes) in the CSF, and high levels of interferon-alpha activity and neopterin in the CSF

Question 36

How does Non-ketotic hyperglycinaemia present?

Answer 36

Clinical manifestations in 1st few days of life (between 6 hr and 8 days after birth). - Poor feeding, failure to suck, lethargy, and profound hypotonia may progress rapidly to a deep coma, apnea, and death. - Convulsions, especially myoclonic seizures and HICUPS, are common.

Question 37

What is the most common mode of inheritance in Alport syndrome?

Answer 37

85% caused by X linked inheritance | 15% Autosomal recessive

Question 38

Syndrome with: ``` Aortic root aneurysm Arterial tortuosity Widespread aneurysms Hypertelorism Cleft palate Broad or bifid uvula Craniosynostosis Midface ```

Answer 38

Loey Dietz Syndrome

Question 39

TGFBR1 or TGFBR2 gene mutation is associated with?

Answer 39

Loeys Dietz Syndrome

Question 40

How can you differentiate Marfans Syndrome and Loeys Dietz syndrome?

Answer 40

Distinction between MFS and LDS is important because aneurysms tend to dissect at younger ages and LDS children have more craniofacial anomalies.

Question 41

Most common cardiac anomalies with Ehlers Danlos?

Answer 41

Valve prolapse

Question 42

What is the most common variant of Ehlers Danlos and how do you differntiate it from the second most common type?

Answer 42

Most common - Hypermobile variant (type III) Second most common - Classic - Type I Differentiate: Hypermobile typically just hypermobile (Beighton score >6) without the other skin manifestations. In the Classic variant - The skin is “velvet” to the touch and is particularly fragile, with minor lacerations forming gaping wounds that leave broad, atrophic, papyraceous (“cigarette paper”) scars. both Autosomal dominant

Question 43

Cowden syndrome presents with multiple hamartomas: Numerous flesh-colored papules also develop on the face, particularly around the mouth, nose, and ears. These papules are most commonly trichilemmomas, a benign neoplasm of the hair follicle. What gene is affected? these can commonly affect - _____ and ______

Answer 43

Breast and thyroid hamartomas Gene effected is PTEN

Question 44

Most commonly associated skin lesion in Russell Silver syndrome?

Answer 44

Cafe au lait spot

Question 45

Most commonly associated syndrome with absent/hypoplastic nasal bone ?

Answer 45

Trisomy 21

Question 46

Which syndrome? Critical gene deletion is TBX1

Answer 46

Velocardiofacial syndrome

Question 47

Along with ectopia lentis, which of the following is a common eye sign seen in Marfans?

Answer 47

Myopia

Question 48

What test would you perform to confirm Fanconi anaemia?

Answer 48

Chromosomal breakage studies

Question 49

Telomere length is used to diagnose....

Answer 49

Dyskeratosis congenita and other syndromes

Question 50

Hearing loss + large platelets + Dohle blodies =

Answer 50

MYH9 thrombocytopenia Can also have glomerular nephropathy, cataracts and derranged LFT's, Dohle bodies (neutrophil inclusion bodies)

Question 51

Best genetic test for PWS?

Answer 51

DNA methylation

Question 52

GNAS mutation is associated with which two conditions?

Answer 52

McCune Albright and pseudohypoparathyroidism McCune Albright - Gain of function of the gene; often somatic Pseudohypoparathyroidism - disorder of inactivation (resistance to PTH hormone) Difference between the two is due to IMPRINTING

Question 53

What is the most common abnormality seen in 16p11.2 deletion?

Answer 53

Autism, ID, mental health issues

Question 54

Aicardi syndrome is associated with Corpus collosum agenesis + ______ (eye sign)

Answer 54

Chorioretinal lacunae Also see infantile spasm

Question 55

Broad thumbs + prominent teeth + downslanting eyes

Answer 55

Rubinstein -Taybi syndrome

Question 56

Which bony changes are associated with NF1?

Answer 56

Sphenoid dysplasia, pseudoarthrosis

Question 57

7 criteria of NF1? CAFE SPO

Answer 57

Cafe au lait Axillary freckling Fibromas Eye - Leisch nodules ``` Skeletal bowing - pseudoarthrosis, sphenoid dysplasia Positive family hx Optic tumour (gliomas) ```

Question 58

Cytosine and Thymine are... Purines or Pyrimidines?

Answer 58

Pyrimidine | Cytosine and Thymine have a y in them

Question 59

Transcription is initiated by which enzyme to the promoter site upstream of the coding sequence of the gene?

Answer 59

RNA polymerase | To start off DNA replication -> you need DNA polymerase

Question 60

What is the role of DNA phosphodiestarase?

Answer 60

Cleaves the backbone of DNA

Question 61

What is the pneumonic for DNA replication and actions? PMAT

Answer 61

P - protophase - Pair M = Metaphase = meet in the middle A - Anaphase - tear apart T = tear

Question 62

What are the two main ways of Epigenetics?

Answer 62

Methylation of DNA or Acetylation of histones (Deactivation of DNA)

Question 63

Bifid Uvula + intellectual development

Answer 63

Shprintzen-Goldberg syndrome | Loeys-Dietz syndrome also have bifid uvula

Question 64

What is the Ghent's criteria?

Answer 64

Used to diagnose Marfans In the absence of family history you need: 1) Aortic root dilatation + one of the following - FBN1 gene mutation - Eye changes - Or systemic score

Question 65

cervical vertebrae fusion and anomalies are seen in...

Answer 65

Klippel-Feil syndrome

Question 66

Maternal UPD 7 =

Answer 66

Russel-Silver syndrome

Question 67

Pleural effusion seen in utero with syndrome...

Answer 67

Noonan syndrome

Question 68

Developmental issues + 2-3 Syndactyl =

Answer 68

Smith Lemli Opitz

Question 69

sensorineural hearing loss + loss of vision (retinitis pigmentosa) who has an autosomal recessive syndrome...`

Answer 69

Usher syndrome

Question 70

Sensorineural hearing loss and long QT syndrome =

Answer 70

Jervell-Lange-Nielson syndrome

Question 71

Broad thumbs and big toes =

Answer 71

Rubinstein Taybi syndrome Orher associated issues - mental disability, shift height, cryptoorchidism and anaesthetic complications

Question 72

CREBBP gene associated with =

Answer 72

Rubenstein-Taybi Syndrome