3 - Genetics Flashcards
What is the extra chromosome in Patau’s and Edward’s?
Puberty, Education, Degree
Patau: Trisomy 13 (rocker bottom feet)
Edward’s: Trisomy 18
Down’s: Trisomy 21
What is predictive testing?
Testing for a mutation of a gene that predicts a disease e.g BRCA1
What processes need to be done before genetic testing?
- Consent
- Genetic counselling
What is Karyotyping?
Looking at the number of chromosomes, their shape and their size
Can diagnosis Downs and Turner’s
What are some other types of genetic testing apart from karyotyping and predictive testing?
- Microarray testing
- Specific gene testing
- DNA sequencing
What are the dysmorphic features found in Down’s syndrome?
- Hypotonia
- Brachycephaly (small head with a flat back)
- Short neck
- Short stature
- Flattened face and nose
- Prominent epicanthic folds
- Upward sloping palpable fissures
- Single palmar crease
What are some co-morbidities associated with Downs Syndrome?
- Learning disability
- Recurrent otitis media
- Deafness and Glue ear
- Visual problems e.g myopia , strabismus and cataracts
- Hypothyroidism occurs in 10 – 20%
- ASD, VSD, PDA and tetralogy of Fallot (affects 1 in 3)
- Type 1 diabetes
- Obstructive sleep apnea
- Duodenal atresia
- Coaeliac disease
- Imperforate anus
- Acute Myeloid Leukaemia
- Dementia
What are the three antenatal screening tests for Downs syndrome?
- Combined
- Triple
- Quadruple
What is the combined test?
- First line
- Most accurate
- 11 to 14 weeks
- US NT>6mm and maternal blood tests (high b-hCG and low PAPPA)
What is the triple test?
- 14 to 20 weeks
- B-HCG: higher result indicates greater risk.
- Alpha-fetoprotein (AFP): lower result greater risk
- Serum oestriol: lower result greater risk
What is the quadruple test?
- 14 to 20 weeks gestation
- Identical to triple test but also includes maternal blood for inhibin-A. A higher inhibin-A indicates a greater risk
What is some diagnostic testing if there is a high risk of Downs on screening?
- Chorionic villus sampling (CVS): US guided biopsy of the placental tissue. Used before 15 weeks
- Amniocentesis: US guided aspiration of some amniotic fluid using a needle and syringe. This is later in pregnancy once there is enough amniotic fluid to make it safer to take a sample
- NIPT: maternal blood test, not diagnostic. Uses cell free DNA
What is the management when a baby is born with Downs syndrome?
Involve the multidisciplinary team
- OT
- Speech and language
- Physiotherapy
- Dietician
- Paediatrician
- GP
- Health visitors
- Cardiologist for congenital heart disease
- ENT
- Audiologists
- Optician for glasses
- Social services for social care and benefits
- Additional support with educational needs
- Charities such as the Down’s Syndrome Association
What routine checkups do children with Downs syndrome need?
- FBC
- Karyotyping
- Thyroid checks every 2 years
- Echocardiogram to diagnose cardiac defects
- Regular audiometry for hearing impairment
- Regular eye checks
What is the life expectancy for somebody with Downs syndrome?
60
Common causes of premature death: infections (e.g. pneumonia) cardiac disease (and CHD) and dementia
What is the aetiology and risk factors for Down syndrome?
Most common genetic cause of learning disability
Aetiology
Trisomy 21 (94-95%): Non disjunction during meiosis
Robertsonian translocation (3-4%): DS may be caused by translocation of the long arm of chromosome 21 to another chromosome, most commonly 14.
Trisomy 21 mosaicism (1-2%):
Risk
Maternal age
Previous child with DS
What is the most to least common cardiac complication with Down syndrome?
- Atrioventricular septal defect (45%)
- Ventricular septal defect (35%)
- Isolated secundum atrial septal defect (8%)
- Isolated persistent patent ductus arteriosus (7%)
- Isolated tetralogy of Fallot (4%)
- Other (1%)
What are some features of Edward’s syndrome and what is the prognosis?
Survive a few months maximum
- Low-set ears
- Micrognathia
- Microcephaly
- Overlapping 4th and 5th fingers
- Rocked bottomed feet
- Congenital heart disease
What are some features of Patau’s syndrome and what is the prognosis?
Survive a few weeks maximum
- Holoprosencephaly
- Cleft lip and palate
- Microcephaly
- Polydactyly
- Congenital heart disease
What is Klinefelter syndrome and some of the features of this?
A male with an additional X chromosome. XXY
Appear male until puberty when they get:
- Taller height
- Wider hips
- Gynaecomastia
- Weaker muscles
- Small testicles
- Reduced libido
- Shyness
- Infertility
- Subtle learning difficulties (particularly affecting speech and language)
How is Klinefelter’s managed?
- Testosterone injections improve many of the symptoms
- IVF for fertility
- Breast reduction surgery
Multidisciplinary team input:
- Speech and language therapy
- Occupational therapy
- Physiotherapy to strengthen muscles and joints
- Educational support
What is the prognosis with Klinefelter’s?
- Infertility (can have IVF)
- Osteoporosis
- Diabetes
- Anxiety and depression
- Breast cancer
What is the prognosis with Klinefelter’s?
Higher risk of:
- Infertility (can have IVF)
- Osteoporosis
- Diabetes
- Anxiety and depression
- Breast cancer
What is Turner’s syndrome and what are some of the features of this?
Female with single X chromosome (45XO)
- Short stature
- Webbed neck
- Broad chest with widely spaced nipples
- High arching palate
- Downward sloping eyes with ptosis
- Cubitus valgus
- Underdeveloped ovaries with reduced function
- Late or incomplete puberty
- Most women are infertile
What are some associated conditions with Turner’s syndrome?
- Recurrent otitis media
- Recurrent UTIs
- Coarctation of the aorta
- Hypothyroidism
- Hypertension
- Obesity
- Diabetes
- Osteoporosis
- Various learning disabilities
How is Turner’s syndrome managed?
- Growth hormone therapy: prevent short stature
- Oestrogen and progesterone replacement: establish female secondary sex characteristics, regulatemenstrual cycle and prevent osteoporosis
- Fertility treatment can increase the chances of becoming pregnant
- Patients need monitoring for the associated conditions and complications
What is Noonan syndrome and what are some of the features of this?
Autosomal dominant genetic condition
- Short stature
- Broad forehead
- Downward sloping eyes with ptosis
- Hypertelorism (wide space between the eyes)
- Prominent nasolabial folds
- Low set ears
- Webbed neck
- Widely spaced nipples
What are some associated conditions with Noonan syndrome?
- Congenital heart disease: pulmonary valve stenosis, hypertrophic cardiomyopathy and ASD
- Cryptorchidism: infertility in males
- Learning disability
- Bleeding disorders
- Lymphoedema
- Increased risk of leukaemia and neuroblastoma
What is the management for Noonan syndrome?
- Support with MDT team
- Corrective surgery for congenital heart defects
What is Marfan’s syndrome and the features of this?
Autosomal dominant condition affecting the fibrillin gene
- Tall stature
- Long neck
- Long limbs
- Long fingers (arachnodactyly)
- High arch palate
- Hypermobility
- Pectus carinatum or pectus excavatum
- Downward sloping palpable fissures
How can you test for arachnodactyl in real life?
- Cross their thumb across their palm, if the thumb tip goes past the opposite edge of the hand this indicates arachnodactyly
- Ask them to wrap the thumb and fingers of one hand around the other wrist, if the thumb and fingers overlap this also indicates arachnodactyly.
What are some associated conditions with Marfan’s?
- Lens dislocation in the eye
- Joint dislocations
- Scoliosis
- Pneumothorax
- GORD
- Mitral valve prolapse (with regurgitation)
- Aortic valve prolapse (with regurgitation)
- Aortic aneurysms
How is Marfan’s syndrome managed?
- Surgical correct any aortic aneurysm/valve prolapse as greatest risk
- Minimise blood pressure and heart rate to minimise the stress on the heart and the risk of complications developing e.g avoid intense exercise, caffeine and other stimulants. Preventative medications such as beta blockers and angiotensin II receptor antagonists can also help reduce the risk of complications
- Physiotherapy to strengthen joints
- Genetic counselling when considering children
What regular follow ups do people with Marfan’s need?
- Yearly echocardiogram
- Yearly opthalmologist review
What is Fragile X syndrome?
Mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome that codes for cognitive development
X-linked so comes from mother
What are the features of Fragile X?
- Delay in speech and language
- Intellectual disability
- Long, narrow face
- Large ears
- Large testicles after puberty
- Hypermobile joints (particularly in the hands)
- Attention deficit hyperactivity disorder (ADHD)
- Autism
- Seizures
How is Fragile X managed?
- MDT
- Treat autism, ADHD and seizures if they occur
- Normal life expectancy
What is Prader-Willi syndrome and some of the features of this?
Loss of functional genes on the Chromosome 15 inherited from the father. This can be due to a deletion of this portion of the chromosome, or when both copies of chromosome 15 are inherited from the mother
- Constant insatiable hunger that leads to obesity
- Poor muscle tone as an infant (hypotonia)
- Mild-moderate learning disability
- Hypogonadism
- Fairer, soft skin that is prone to bruising
- Mental health problems, particularly anxiety
- Dysmorphic features
- Narrow forehead
- Almond shaped eyes
- Strabismus
- Thin upper lip
- Downturned mouth
How is Prader Willi syndrome managed?
- Carefully limiting access to food under guidance of a dietician is required to control weight. Under dietician guidance they usually require a lower than normal calorie intake, particularly as they tend to have lower activity levels due to poor muscle strength and tone
- Growth hormone to improve muscle development and body composition
What is Angelman syndrome and the features of this?
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
- Delayed development and learning disability
- Severe delay or absence of speech development
- Coordination and balance problems (ataxia)
- Fascination with water
- Happy demeanour
- Inappropriate laughter
- Hand flapping
- Abnormal sleep patterns
- Epilepsy
- Attention-deficit hyperactivity disorder
- Dysmorphic features
- Microcephaly
- Fair skin, light hair and blue eyes
- Wide mouth with widely spaced teeth
How is Angelman syndrome managed?
- Parental education
- Social services and support
- Educational support
- Physiotherapy
- Occupational therapy
- Psychology
- CAMHS
- Anti-epileptic medication where required
What is William syndrome and some of the features of this?
Deletion of genetic material on one copy of chromosome 7.
Usually the result of a random deletion around conception, rather than being inherited from an affected parent.
- Broad forehead
- Starburst eyes (a star-like pattern on the iris)
- Flattened nasal bridge
- Long philtrum
- Wide mouth with widely spaced teeth
- Small chin
- Very sociable trusting personality
- Mild learning disability
What are some associated conditions with William syndrome?
- Supravalvular aortic stenosis
- ADHD
- Hypertension
- Hypercalcaemia
What is the management of William syndrome?
- MDT approach with support for family
- Echocardiograms and blood pressure monitoring are important to assess for aortic stenosis and hypertension
- Low calcium diet to control hypercalcaemia, and avoid calcium and vitamin D supplements.
How do we draw a family tree?
If somebody with Down syndrome develops leukaemia, what is it likely to be?
- Before age 3: AML
- After age 3: ALL
What are intraventricular haemorrhages and what are the signs of this?
Usually in preterm infants (weight <1500g) due to unsupported blood vessels in the subependymal germinal matrix and the instability of blood pressure associated with birth trauma and respiratory distress
Delayed cord clamping may decrease risk
Signs: Seizures, bulging fontanelle and cerebral irritability but many will have no clinical symptoms
What is the sequale associated with intraventricular haemorraghe?
- Low IQ
- Hydrocephalus
- Cerebral palsy
What are some risk factors for cleft lip and palate?
- Idiopathic
- Relative with cleft palate
- Maternal antiepileptic use
- Cystic fibrosis
What are some complications of a cleft lip or cleft palate?
- Feeding difficulties
- Speech issues
- Psychosocial issues
- Increased risk of otitis media, hearing problems and glue ear
How is cleft lip and palate managed?
- Referred to the local cleft lip services for MDT
- Specially shaped bottles and teats so can feed
- Surgical correction: cleft lip at 3 months, cleft palate at 6-12 months
What is tongue tie and how may it present?
- Shortened lingual frenulum
- May be spotted on newborn baby check
- May have difficulties feeding
How is tongue tie managed?
Frenotomy
What are some differentials for a neck mass in children?
- Thyroglossal duct cyst
- Branchial cyst
- Cystic hygroma
- Teratoma
- Thyroid mass
- Lymphadenopathy
What is a cystic hygroma and how does it present?
- Malformation of the lymphatic system that results in a cyst filled with lymphatic fluid
- Usually posterior triangle on left side of neck, or armpit
- They are soft, non tender and transilluminate
What are the complications of cystic hygromas and how are they managed?
Complications
- Feeding, swallowing or breathing difficulties
- Can become infected or haemorrhage into cyst
Management
- Watch and wait
- Aspiration (giving temporary improvement)
- Surgical removal
- Sclerotherapy
What is a thyroglossal cyst and how does it present?
Midline of the neck, usually infra hyoid. They are:
- Mobile
- Non-tender
- Soft
- Fluctuant
Thyroglossal cysts move up and down with movement of the tongue
How are thyroglossal cysts diagnosed and managed?
Diagnosis
- Moves up on tongue protrusion
- US or CT
Management
- Surgical removal and histology
- Antibiotics for infection
What is a branchial cyst?
- Congenital abnormality when second branchial cleft fails to properly close so fills with fluid
- Round, soft, cystic swelling between the angle of the jaw and the sternocleidomastoid muscle in the anterior triangle of the neck.
- Present after the age of 10 years
What are some features of a branchial cyst and how does it appear differently to a cystic hygroma?
Appears later and does not transilluminate!
- Unilateral
- Anterior to the sternocleidomastoid muscle
- Slowly enlarging
- Smooth, soft, fluctuant
- Non-tender
- Fistula may be seen
- No movement on swallowing
- No transillumination
What are some differentials for a branchial cyst?
- Congenital: branchial cyst, thyroglossal cyst, dermoid cyst, vascular malformation
- Inflammatory: reactive lymphadenopathy, lymphadenitis
- Neoplastic: lymphoma, thyroid tumour, salivary gland tumour
How are branchial cysts diagnosed and managed?
Diagnosis:
- Refer to ENT
- US and FNA to exclude other malignancy
Mx
- Conservative management if no cosmetic or other issues
- Antibiotics for infections
- Surgical excision
