Genetics Flashcards
What is the craniofacial appearance in Down syndrome?
Round face Flat nasal bridge Upslanted palpebral fissures Epicanthic folds Brushfield spots in iris Small mouth and protruding tongue Small ears Third fontanelle Flat occiput
What are the non-facial features of Down syndrome?
Short neck Hypotonia Single palmar crease Incurved 5th finger Sandal gap Congenital heart disease (AVSD) Duodenal atresia Hirschsprung disease
What are the possible complications of Down syndrome?
Delayed motor milestones
Moderate to severe learning difficulties
Short stature
Increased susceptibility to infections
Congenital heart disease, particularly AVSD
Hypothyroidism
Hearing impairment from secretory otitis media
Visual impairment from cataracts, squints, myopia
Increased risk of leukaemia and solid tumours
Atlanto-axial instability
Coeliac disease
Epilepsy
Alzheimer’s disease
What is the defect in Edwards?
Trisomy 18
What are the features of Edwards?
Low birthweight Prominent occiput Small mouth and chin Short sternum Fixed, overlapping fingers 'Rocker-bottom' feet Cardiac and renal malformations
What is the defect in Patau?
Trisomy 13
What are the features of Patau?
Structural defect of brain e.g. holoprosencephaly Scalp defects Microphthalmia and other eye defects Cleft lip and palate Polydactyly Cardiac and renal malformations
What is the defect in Turner syndrome?
45X
What are the signs found in Turner syndrome?
Lymphoedema of hands and feet in neonate which may persist Spoon shaped nails Short stature Neck webbing or thick neck Wide carrying angle (cubitus valgus) Widely spaced nipples Pigmented moles
What are the complications/associations with Turner syndrome?
Congenital heart defects: particularly coarctation of the aorta Delayed puberty Ovarian dysgenesis causing infertility Pregnancy may be possible with IVF with donated eggs Hypothyroidism Renal anomalies Recurrent otitis media Normal intellectual function in most
What is the risk of recurrence like in Turner syndrome?
low
How is Turner syndrome treated?
GH therapy and oestrogen replacement at puberty, plus management of any complications
What is the defect in Klinefelter syndrome?
47XXY
What are the features of Klinefelter syndrome?
Infertility (most common presentation)
Hypogonadism with small testes
Pubertal development my appear normal but some males benefit from testosterone therapy
Gynaecomastia in adolescence
Tall stature
Intelligence usually normal range but some have educational and psychological problems
What is the risk of recurrence like in Klinefelter?
Low
What is the defection fragile X?
CGG trinucleotide repeat
How is fragile X inherited?
X-linked recessive, but 1/5 males who inherit the mutation are phenotypically normal and some female carriers have mild to moderate learning difficulties
What are the clinical features of fragile X in males?
Moderate-severe learning difficulty (mean IQ 50) Macrocephaly Postpubertal macro-orchidism Characteristic facies Mitral valve prolapse Joint laxity Scoliosis Autism Hyperactivity
What are the characteristic facial features of fragile X?
Long face
Large everted ears
Prominent mandible
Broad forehead
What is the defect in Angelman syndrome?
80% deletion on maternal chromosome 15
2-3% paternal uniparental disomy 15
Remainder due to stable mutations
What are the clinical features of Angelman syndrome
Unprovoked laughter/clapping Microcephaly Severe learning disability Ataxia Broad-based gait Seizures Characteristic EEG
What is the defect in Alagille syndrome?
Deletion or mutation of JAG1 gene on chromosome 20
How is Alagille inherited?
Variable autosomal dominant
What are the major features of Alagille syndrome?
Cardiac: peripheral pulmonary artery stenosis ± complex malformations
Eye: posterior embryotoxon, abnormalities of the anterior chamber
Vertebral: butterfly vertebrae, hemivertebrae, rib anomalies
Hepatic: cholestatic jaundice, paucity of intrahepatic bile ducts
What is Goldenhar syndrome also known as?
oculo-auriculovertebral spectrum, or 1st and 2nd and branchial arch syndrome
How is Goldenhar inherited?
Mainly sporadic
What are the major features of Goldenhar syndrome?
Craniofacial: asymmetry, hemifacial microsomia, micrognathia
Ears: malformed pinnas, deafness, preauricular tags
Eyes: epibulbar (scleral) dermoid cysts, microphthalmia
Oral: macrostomia, cleft lip/palate
Vertebral: hemivertebrae
Cardiac: cardiac malformations
Renal: renal malformations
What is the principal feature in Proteus syndrome?
Asymmetric and disproportionate overgrowth of body parts with is progressive
What are the possible cutaneous findings in Proteus syndrome
Capillary, lymphatic or venous malformations Naevi Lipomas Café-au-lait macules Hypertrichotic patches
How is Noonan syndrome inherited?
Autosomal dominant
What is the mutation in Noonan syndrome?
All involve Signalling through RAS, but several different gene associations
What are the clinical features of Noonan syndrome?
Characteristic facies Short webbed neck with trident hairline Pectus excavatum Short stature Congenital heart disease, especially pulmonary stenosis and atrial septal defect, hypertrophic cardiomyopathy Variable developmental problems
Which syndromes are associated with a 22q11.2 deletion?
DiGeorge Velocardiofacial/Shprintzen syndrome Conotruncal anomaly face Caylor cardiofacial Autosomal dominant Opitz
What are the main features of a 22q11 microdeletion?
Parathyroid hypoplasia with hypocalcaemia
Thymus hypoplasia with T lymphocyte deficiency
Congenital cardiac malformations especially interrupted aortic arch and truncus arteriosus
Cleft palate
Learning disability
What is the defect in Williams syndrome?
Microdeletions involving the elastin gene on chromosome 7
What are the main features of Williams syndrome?
Short stature Characteristic facies Transient neonatal hypercalcaemia Congenital heart disease (supravalvular aortic stenosis) Mild to moderate learning difficulties
What is the defect in Prader Willi syndrome?
70% deletion on paternal chromosome 15
30% maternal uniparental disomy 15
What are the clinical features of Prader Willi syndrome?
Characteristic facies Hypotonia Neonatal feeding difficulties Failure to thrive in infancy Obesity in later childhood Hypogonadism Developmental delay Learning difficulties
What are the characteristic facial features in Prader will
Prominent nasal bridge
High, narrow forehead
Thin upper lip
Downturned mouth
