Genetics Flashcards
What is the first, second and third most common inheritance pattern for Down’s Syndrome?
Non-dysjunction
Robertsonian Translocation (onto Chromosome 14)
Mosaicism
What chromosome is affected in Cri-du-chat?
Chromosome 5, (5p deletion)
What chromosome is affected in DiGeorge Syndrome?
Chromosome 22
What chromosome is affected in Charcot Marie Tooth Syndrome?
Chromosome 17
What are the manifestations of Down’s Syndrome in the face, eyes, ears, mouth, hands, feet, brain, spine, endocrine, lungs, heart, gastrointestinal, gynaecological and haematological?
- Face: Flat facial features, flat occiput
- Eyes: Brushfield spots, upward sloping palpebral fissures, prominent epi-canthal folds
- Ears: Low set ears, Hearing loss, glue ear
- Mouth: Protruding tongue
- Hands: Single palmar crease
- Feet: Widened sandal gap
- Brain: Alzheimer’s, Learning Disabilities
- Spinal: Altanto-axial instability
- Endocrine: Hypothyroidism
- Respiratory: Respiratory infections
- Cardiac: ASD, VSD, PDA, Tetralogy of Fallot
- Gastrointestinal: Hirschprung’s Disease, Duodenal atresia
- Gynaecological: Subfertility
- Haematological: Acute Lymphoblastic Leukaemia
What are all the Antenatal Screening tests for Down’s Syndrome?
- Combined
- Triple
- Quadruple
Outline the Combined test for Down’s Syndrome
- When is it performed?
- What does it test?
Performed at 11-14 weeks gestation
Comprises the Ultrasound & Maternal Blood Test
- Ultrasound, increased nuchal translucency >6mm
2a. Beta-hCG, higher result, greater risk
2b. PAPP-A, lower result, greater risk
Outline the Triple test for Down’s Syndrome
- When is it performed?
- What does it test?
Performed at 14-20 weeks gestation
Comprises only Maternal Blood Tests
1a. Beta-hCG, higher result, greater risk
1b. Serum Oestriol, lower result, greater risk
1c. AFP, lower result, greater risk
Outline the Quadruple test for Down’s Syndrome
- When is it performed?
- What does it test?
Performed at 14-20 weeks gestation
Comprises only Maternal Blood Tests
1a. Beta-hCG, higher result, greater risk
1b, Serum Oestrial, lower result, greater risk
1c, AFP, lower result, greater risk
1d. Inhibin-A, higher result, greater risk
Once Antenatal Screening Down’s Syndrome tests have been performed, what is done with the result?
Screening tests will give a risk score for the foetus having Down’s Syndrome. If risk > 1 in 150, will be offered CVS (if before 15 weeks) and Amniocentesis (later in pregnancy)
What is Klinefelter’s Syndrome?
Hypergonadotrophic Hypogonadism, 47XXY
What are some features of Klinefelter’s Syndrome?
Small testicles Weaker muscles Weak bones Gynaecomastia Wide hips Tall height
What are the hormonal test results of Klinefelter’s Syndrome?
Increased LH, FSH, reduced Testosterone
What are patients with Klinefelter’s at an increased risk of?
Diabetes
Osteoporosis
Breast Cancer
What is the treatment for Klinefelter’s?
Testosterone Injections
What is the Karyotype for Turner’s Syndrome? What is the most common genetic mutation?
45,XO, commonly due to non-dysjunction
What is the clinical presentation of Turner’s Syndrome with respect to height, face, neck, endocrine, heart, chest, arms, hands, feet, renal, gynaecological
Height: Short stature Face: Low set, ears Neck: Webbed, Cystic Hygroma Endocrine: Hypothyroidism Heart: Coarctation of Aorta, Bicuspid Valve Chest: Broad chest, Widely spaced nipples Arms: Cubitus valgus Hands: Lymphadema, short 4th metacarpal Feet: Lymphadema Renal: Horseshoe kidney Gynaecological: Primary Amenorrhoea
What are the features of Noonan Syndrome? 5, 4, 4
5, 4, 4
5: Webbed Neck, Triangular face, Short stature, Pectus Excavum, Undescended Testis
4 HIPA: Hypertrophic cardiomyopathy Infundibular Pyloric Stenosis Pulmonic Stenosis, Pulmonary HTN Atrial Septal Defect
4: Autosomal dominant, Strabismus, Downward Palpebral Fissure, Factor XI Deficiency
What are the features of Patau Syndrome?
Microcephaly
Holoproscencephaly
Meningomyelocele
Omphalcele
Cutis aplasia Microphthalmia Polydactyl Cleft lip palate Rocker bottom feet Cyclopsia Nose missing + Proboscis
What is the biggest risk factor for Patau Syndrome?
Advanced Maternal Age
Fragile X is a mutation of which gene? What is the inheritance pattern?
FMR1 gene: Fragile Mental Retardation 1 gene
X-linked inheritance pattern
Why are men always affected in Fragile X Syndrome and women variably affected?
Men are always affected because they only have one copy of the mutated FMR1 gene, whereas women have one normal copy of the FMR1 gene as well
What cardiac problem is associated with Fragile X Syndrome?
Mitral Valve Prolapse
What are features of Fragile X Syndrome?
Long narrow face, large ears, high arched palate, hypermobile joints, macro-orchidism, mitral valve prolapse, learning difficulties, autism, ADHD, seizures
Describe the mutation of the FMR1 gene in Fragile X Syndrome
CCG Expansion repeats due to slipped mispairing. >200 repeats is diagnostic
What does it mean when a patient is a pre-mutation carrier of Fragile X Syndrome?
They have between 55 and 200 CCG CCG repeats. This can cause Fragile X Associated Tremor Ataxia Syndrome or Primary Ovarian Insufficiency
Prader-Willi Syndrome affects which Chromosome?
Chromosome 15
Outline the genetics of Prader-Willi Syndrome
Prader-Willi Syndrome is a genetic condition thats affects genes on Chromosome 15. Regarding this gene, in normal cases the mother’s genes are epigenetically switched off due to methylation, meaning the father’s genes only contribute to the phenotype (imprinting). However, the father’s genes in PWS are micro-deleted (70%) of cases. In 30% of other cases, PWS is caused because the child inherits both switched off copies of maternal genes (Maternal uniparental disomy)
What is the presentation of Prader-Willi Syndrome in:
Newborns, Infants and Childhood?
Newborns: HYPOTONIA, poor sucking reflex hence FTT. Narrow forehead, almond eyes, thin upper lip, downturned mouth, fairer softer skin prone to bruising
Infants: Insatiable hunger due to hypothalamic dysfunction
Childhood: Short stature, morbidly obese, T2D, obstructive sleep apnoea. learning difficulties / low IQ,
What gene and what chromosome is affected in Angleman Syndrome?
UBE3A Gene, Chromosome 15
Outline the genetics of Angleman Syndrome
Angelman syndrome is a genetic condition caused by loss of function of the UBE3A gene, specifically the copy of the gene that is inherited from the mother. This can be caused by a deletion on chromosome 15, a specific mutation in this gene or where two copies of chromosome 15 are contributed by the father, with no copy from the mother.
Outline features of Angleman Syndrome
Fascination with water, shiny objects
Widely spaced teeth
Excessive positive affect
Inappropriate laughter
Outline features of Cri-du-Chat Syndrome
Cat-like cry Small round face Large cheeks Hypertelorism (widely spaced eyes) Prominent supraorbital arches Epicanthal folds Dropped jaw Dental malocclusion
What are the dysmorphic features of Edward’s Syndrome in the face, hands, feet?
Face: Prominent Occiput, Microcephaly, Cleft lip palate, Micrognathia (small chin)
Hands: Overlapping fingers
Feet: Rocker bottom feet
What is the prognosis of Edward’s Syndrome?
Most babies die before birth, those who survive birth will however die within weeks / months due to central apnoea and severe cardiac abnormalities
Why do babies with Edward’s Syndrome have polyhydramnios?
Because they have oesophageal atresia, hence cannot swallow amniotic fluid
What are some multi-organ manifestations (cardiac, renal, hepatic, respiratory, gastrointestinal) of Edward’s Syndrome?
Cardiac: ASD, VSD, PDA Renal: Nephroblastoma, horseshoe kidney Hepatic: Hepatoblastoma GI: Oesophageal atresia, Omphalcele Respiratory: Pulmonary hypoplasia
What is the quatrad for Pierre-Robin Sequence / Syndrome?
Micrognathia (underdeveloped jaw), Glossoptosis (posterior displacement of tongue), Airway obstruction and Cleft palate deformity
What are the features for William Syndrome?
Elfin facies, starburst eyes, sociable, short stature, and spaced teeth
What are the four complications for William Syndrome? SAHH
Supravalvular Aortic Stenosis
ADHD
Hypertension
Hypercalcaemia
What conditions are tested for with the Guthrie test? When is it performed, and when do results come?
My Middle Child Cried Since I Harshley Guthrie Pricked
Maple Syrup Urine Disease Medium Chain Acyl-CoA Dehydrogenase Deficiency Cystic Fibrosis Congenital Hypothyroidism Sickle Cell Disease Isovaleric Acidaemia Homocysteinuria Glutaric Aciduria Type 1 Phenylketonuria
Taken on days 5-9, and results come back in 6-8 weeks
