Genetics Flashcards
PAX 2 gene is associated with ____
Renal-Coloboma syndrome
CHD7 mutation is associated with _____
Charge syndrome
ATP7B associated with _____
Wilson’s disease
SERPINA 1 related to ______
Alpha 1 antitrypsin deficiency
UBE3A related to ______
Angelman syndrome
DHCR7 related to ____
Smith-Lemli-Opitz Syndrome
Abnormal architecture of the vitreous gel is pathognomonic of _____
Stickler syndrome
Usher syndrome is associated with hearing loss but also _______________
ataxia and retinitis pigmentosa
Children with Pendred syndrome have a _______ associated with deafness
Goitre
Features of Alport syndrome are ______, ______ and _______
Features of Alport syndrome are nephritis, deafness and retinitis.
Describe the syndrome:
1 in 16,000 live births, Holoprosencephaly, cutis aplasia, midline defects, microphthalmia, coloboma, polydactyly/clenched hand
Trisomy 13 - Patau Syndrome
Describe the syndrome:
1 in 8,000 live births,
Hypertonia, arthrygrpossis, Rocker-bototm feet, overlapping fingers, omphalocoele, diaphragmatic hernia, severe mental retardation
Trisomy 18 - Edwards Syndrome
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
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
Describe the syndrome:
1 in 1000
Tall stature, low IQ, Hypergonanadotrophic hypogonadism (small testes, infertile), gynaecomastia
Also what percentage have congenital heart disease?
Kleinfelters syndrome XXY
50% have CHD - ASD and PDA
Describe the syndrome:
1 in 4000
Cardiac anomalies, hypocalcaemia, thymic aplasia
What is the most common mental health disorder?
22q.11 microdeletion
30 fold increased risk of schizophrenia
Describe the syndrome:
1in 1,000-2,500
Short stature, hypertelorism, refractor errors, small upturned noses, low set posteriorly rotated ears
Noonan syndrome
In Noonan’s Syndrome 70% deletion mutation in ____________
70% deletion mutation in RAS/Mitogen activated protein kinase signalling pathway
Marfans syndrome is a result of ______ protein mutation in chromosome __
FBN1 gene mutation for Fibrillin in chromosome 15
What ocular anomaly is noted in Marfans syndrome?
Ectopia Lentis
(Up and in)
Homocysteinuria also has Ectopia Lentis but down and out
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
Cleidocranial dysplasia
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)
Autosomal dominant condition
Stickler syndrome (30-50% of Pierre Robin sequence have this)
15q 11-13 maternal deletion syndrome = ________
15q11-13 paternal deletion syndrome = _________
15q 11-13 maternal deletion syndrome = Angelman syndrome
15q11-13 paternal deletion syndrome = Prader-Willi syndrome
_________ 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
Angelman syndrome
Most common genetic defect for Angelman syndrome?
Gene deletion in 70% cases
What is the genetic testing for Angelman syndrome?
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
_______ syndrome is characterized by hypotonia, poor feeding in infancy with failure to thrive but increased appetite and obesity in children and adults.
Prader Willi Syndrome
Also seen is genital hypoplasia, small hands and feets
What are the two most common genetic defects that contribute towards Prader Willi Syndrome?
Deletion of paternal 15q11.2-13 – 50 to 75 percent of cases.
Maternal uniparental disomy – 20 to 50 percent of cases.
What are the most common features of PWS:
- In infancy/neonate:
- School age children:
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%
_______________ 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.
Kearns- Sayre syndrome
Also associated with autoimmune thyroid, adrenal disease, and diabetes; and cardiac conduction defects
mental retardation
autistic behaviour
macro-orchidism
facial features – long face, large cupped ears, prominent square jaw
Which syndrome?
Fragile X
Name 4 common triple repeat disorders?
1) Fragile X - CGG
2) Huntington’s disease - CAG
3) Fredreich’s Ataxia - GAA
4) Myotonic dystrophy - CTG
5) Spinocerebellar ataxia - CAG
PTPN11 or RAS-mitogen activated protein kinase (MAPK) is associated with which syndrome?
Noonan syndrome
Short palpebral fissues, long, smooth philtrum, thin vermillon border, maxillary hypoplasia and ptosis….
Fetal alcohol syndrome
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)
Menke disease
X-linked recessive trait. The Menkes gene, ATP7A, on Xq21.1,
Alongside cerebral calcifications and a family history; what lab markers on CSF might you see for Aicardi Goutieres syndrome?
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
How does Non-ketotic hyperglycinaemia present?
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.
What is the most common mode of inheritance in Alport syndrome?
85% caused by X linked inheritance
15% Autosomal recessive
Syndrome with:
Aortic root aneurysm Arterial tortuosity Widespread aneurysms Hypertelorism Cleft palate Broad or bifid uvula Craniosynostosis Midface
Loey Dietz Syndrome
TGFBR1 or TGFBR2 gene mutation is associated with?
Loeys Dietz Syndrome
How can you differentiate Marfans Syndrome and Loeys Dietz syndrome?
Distinction between MFS and LDS is important because aneurysms tend to dissect at younger ages and LDS children have more craniofacial anomalies.
Most common cardiac anomalies with Ehlers Danlos?
Valve prolapse
What is the most common variant of Ehlers Danlos and how do you differntiate it from the second most common type?
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
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 ______
Breast and thyroid hamartomas
Gene effected is PTEN
Most commonly associated skin lesion in Russell Silver syndrome?
Cafe au lait spot
Most commonly associated syndrome with absent/hypoplastic nasal bone ?
Trisomy 21
Which syndrome?
Critical gene deletion is TBX1
Velocardiofacial syndrome
Along with ectopia lentis, which of the following is a common eye sign seen in Marfans?
Myopia
What test would you perform to confirm Fanconi anaemia?
Chromosomal breakage studies
Telomere length is used to diagnose….
Dyskeratosis congenita and other syndromes
Hearing loss + large platelets + Dohle blodies =
MYH9 thrombocytopenia
Can also have glomerular nephropathy, cataracts and derranged LFT’s, Dohle bodies (neutrophil inclusion bodies)
Best genetic test for PWS?
DNA methylation
GNAS mutation is associated with which two conditions?
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
What is the most common abnormality seen in 16p11.2 deletion?
Autism, ID, mental health issues
Aicardi syndrome is associated with Corpus collosum agenesis + ______ (eye sign)
Chorioretinal lacunae
Also see infantile spasm
Broad thumbs + prominent teeth + downslanting eyes
Rubinstein -Taybi syndrome
Which bony changes are associated with NF1?
Sphenoid dysplasia, pseudoarthrosis
7 criteria of NF1?
CAFE SPO
Cafe au lait
Axillary freckling
Fibromas
Eye - Leisch nodules
Skeletal bowing - pseudoarthrosis, sphenoid dysplasia Positive family hx Optic tumour (gliomas)
Cytosine and Thymine are…
Purines or Pyrimidines?
Pyrimidine
Cytosine and Thymine have a y in them
Transcription is initiated by which enzyme to the promoter site upstream of the coding sequence of the gene?
RNA polymerase
To start off DNA replication -> you need DNA polymerase
What is the role of DNA phosphodiestarase?
Cleaves the backbone of DNA
What is the pneumonic for DNA replication and actions?
PMAT
P - protophase - Pair
M = Metaphase = meet in the middle
A - Anaphase - tear apart
T = tear
What are the two main ways of Epigenetics?
Methylation of DNA
or
Acetylation of histones
(Deactivation of DNA)
Bifid Uvula + intellectual development
Shprintzen-Goldberg syndrome
Loeys-Dietz syndrome also have bifid uvula
What is the Ghent’s criteria?
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
cervical vertebrae fusion and anomalies are seen in…
Klippel-Feil syndrome
Maternal UPD 7 =
Russel-Silver syndrome
Pleural effusion seen in utero with syndrome…
Noonan syndrome
Developmental issues + 2-3 Syndactyl =
Smith Lemli Opitz
sensorineural hearing loss + loss of vision (retinitis pigmentosa) who has an autosomal recessive syndrome…`
Usher syndrome
Sensorineural hearing loss and long QT syndrome =
Jervell-Lange-Nielson syndrome
Broad thumbs and big toes =
Rubinstein Taybi syndrome
Orher associated issues - mental disability, shift height, cryptoorchidism and anaesthetic complications
CREBBP gene associated with =
Rubenstein-Taybi Syndrome
