Genetic Syndromes Flashcards
Common Genetic Disorders
Down Syndrome -> Trisomy 21 Edwards Syndrome -> Trisomy 18 Patau Syndrome -> Trisomy 13
Common Sex Chromosome Disorders
Fragile X Syndrome
-> CGG Trinucleotide repeat on X chromosome
-> Most common genetic cause of intellectual disability in boys
Klinefelter’s Syndrome
-> 47 XXY (most common)
Turner Syndrome
-> 45X (most common)
Noonan Syndrome
-> 46XX or 46XY
-> Autosomal dominant (not a sex chromosome disorder) with variable expression
Other Genetic Syndromes
DiGeorge Syndrome
-> Microdeletion of 22q11
-> Second most common genetic disorder after DS
Prader-Willi Syndrome
-> No paternally imprinted genes on chromosome 15q11
Angelman Syndrome
-> No maternally imprinted genes on chromosome 15q11
CHARGE Syndrome
-> 2/3 of children have CHD7 mutation on chromosome 8
DiGeorge Syndrome
CATCH 22 Cyanotic CHD Anomalies: micrognathia and low set ear Thymic hypoplasia “immunodeficiency” - recurrent infections Cognitive Impairment Hypoparathyroidism, hypocalcaemia 22q11 microdeletions
Prader-Willi Syndrome
H40 Hyperphagia (Obsessive) Hypotonia and weakness Hypogonadism Hypopigmentation Obesity, DM2 Short stature, almond shaped eyes, small hands and feet with tapering of fingers Developmental delay (variable)
Angelman Syndrome
Severe intellectual disability Seizures Tremulousness Uncontrollable laughter Fair hair Hypotonia Midface hypoplasia
CHARGE Syndrome
CHARGE C - Coloboma H - congenital Heart disease A - choanal Atresia R - mental Retardation G - GU anomalies E - Ear anomalies
Epidemiology of Down’s Syndrome
1:600-800 of births with increased risk with age. At 20 there is a 1:2000 risk and 1:20 by the age of 45.
Aetiology of Down’s Syndrome
Trisomy 21 (47, +21)
- ~94%. An extra chromosome 21 is present
Robertsonian Translocation (Involving chromosome 21)
- ~3-4%
Trisomy 21 mosaicism (47, +21/46)
- ~2-3%. There are two populations of cells, one with the normal 46 chromosomes, the other with 47, +21
Pathophysiology of Down’s Syndrome
Errors in meiosis are almost all maternal origin, although 5% occur during spermatogenesis.
Clinical Presentation of Down’s Syndrome
Head
- Slanted palpebral fissures
- Anomalous ears (low lying ears)
- Flat facial profile
- Excessive skin at nape of the neck
Hands
- Transverse palmar (Simian) crease
- Dysplasia of mid phalanx of the fifth finger
Joints
- Hyper-flexibility of joints
- Hypotonia
- Dysplasia of pelvis
Other
- Poor Moro reflex
Associated Problems of Down’s Syndrome
- Thyroid conditions
- Congenital Heart Disease
- Hearing loss (60%) with otitis media a frequent problem
- Lung problems (lung capacity is reduced in almost 100%),
- Asthma and sleep apnoea
- Eye problems (40%)
- Refractive errors, strabismus, nystagmus
- Digestive problems (6%)
- Duodenal atresia/stenosis
- Imperforate anus
- Oesophageal atresia with tracheoesophagael fistula
- Leukaemia (1%)
- Intellectual Disability
- Infertility (male)
- due to impaired spermatogenesis
- Small stature
- Alzheimer’s Dementia (50% of adult survivors)
- Anxiety and depression
Management of Down’s Syndrome
- Plot growth on charts
- Echocardiogram
- Hearing screen
- Ophthalmologic screen
- TFTs
- Monitor for coeliac
- Monitor for leukaemia
- Monitor for iron deficiency anaemia
- Neurological evaluation
- Monitor for sleep apnoea
Prognosis of Down’s Syndrome
- Average age about 55 years
- 44% survive to 60 years of age
- 50% of adults develop Alzheimer’s dementia
Antenatal Investigations for Down’s Sydnrome
- Screening tests (both first trimester)
- > Combined Test (gold standard of screening)
- > Quadruple and Triple Tests
- Diagnostic Tests
- > Chorionic Villus Sampling (CVS)
- > Amniocentesis
