Genetics Flashcards
Klinefelters genotype
XXY
What feature do more than half of boys present at puberty with Klinefelters?
Gynaecomastia
Small testes and infertility occurs in which genetic condition?
Klinefelters
A man presents with:
- Taller height
- Wider hips
- Gynaecomastia
- Weaker muscles
- Small testicles
- Reduced libido
- Shyness
- Infertility
- Subtle learning difficulties (particularly affecting speech and language)
Possible underlying genetic condition?
Klinefelters syndrome
Name a management option for Klinefelters syndrome
- Testosterone injectionsimprove many of the symptoms
- Advanced IVF techniqueshave the potential to allow fertility
- Breast reduction surgeryfor cosmetic purposes
Tall boy with femine features. Genetic condition?
Klinefelters syndrome
Genetic condition with trisomy 13
Patau syndrome
Which genetic syndrome presents with dysmorphic features and structural abnormalities such as ‘rocker bottom feet’?
Patau syndrome
A baby presents with:
- Microencephay
- Cleft lip/palate
- CHD
- Renal abnormalities
- Post-axial polydactyly
- Severe or profound mental retardation
Patau syndrome
Trisomy 18 genetic condition?
Edward’s syndrome
(Think of Edward an 18 year old)
A baby presents with:
- Small for gestational age
- CHD
- Rocker bottom feet
- Short sternum
- Overriding fingers
Possible underlying genetic condition?
Edward’s syndrome
How are the majority of Nooan syndrome cases inherited?
Autosomal dominant
A child presents with:
- 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
Possible underlying genetic condition?
Noonan syndrome
What is the main complication of Noonan syndrome?
Congenital heart disease, particularly pulmonary valve stenosis
What is the genotype for William syndrome?
A random microdeletion on chromosome 7q11
What are the clinical manifestations of William syndrome?
- 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
A child presents with a very sociable personality, a big smile with a wide mouth and on closer inspection you notice starbust eyes. Possible underlying genetic condition?
William syndrome
What are the 2 main associated conditions with William syndrome?
- Supravalvular aortic stenosis (narrowing above the aortic stenosis)
- Hypercalcaemia
Name a management option for William Syndrome?
- Echocardiograms
- BP monitoring
- Low calcium diet
What are the gene changes in Prader-Willi Syndrome?
Functional gene loss on chromosome 15 inherited from father
(Or both copies inherited from mother)
What are the clinical manifestations of Prader-Willi syndrome?
- Constant insatiable hungerthat 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
A young child presents with truncal obesity, mild-moderate learning difficulties, short stature and an insatiable appetite. Possible underlying genetic condition?
Prader- Willi syndrome
An infant initially presents with a challenging feeding (floppy when feeding) (may be failing to thrive), but then has significant food-seeking behaviour. Possible underlying genetic condition?
Prader-Willi syndrome
What is the management for Prader-Willi syndrome?
Growth hormone
(Improves muscle development and body composition)
What is Fragile X syndrome caused by?
A mutation in the FMR1 gene
(fragile X mental retardation 1)
(Codes for the fragile X mental retardation protein → plays a role in cognitive development in the brain)
What is the inheritance pattern of the FMR1 gene?
X-linked
(unclear whether its recessive or dominant)
What domains of development are delayed in fragile X syndrome?
Speech and language development
A child presents with:
- Intellectual disability
- A long, narrow face and large ears
- He also experiences seizures
What is a possible underlying genetic condition?
Fragile X syndrome
Name 4 features of Fragile X syndrome
- Intellectual disability
- Long, narrow face
- Large ears
- Large testicles after puberty
- Hypermobile joints (particularly in the hands)
- Attention deficit hyperactivity disorder (ADHD)
- Autism
- Seizures
Are males or females always affected in Fragile X syndrome?
Males
(Females can vary how much they are affected)
This is because females have a spare normal copy of the FMR1 gene on their other X chromosome. When the mother is phenotypically normal, the affected child may have inherited the X chromosome from their mother, or it may result from a de novo (random) mutation.
What is the genotype for Turner’s syndrome?
XO
(Females have a single X chromosone)
A young girl presents with short stature, webbed neck and widely spaced nipples. What is a possible underlying genetic condition?
Turner’s syndrome
What is the elbow deformity associated with Turner’s syndrome
Cubitus valgus
What are features of Turner’s syndrome?
- Short stature
- Webbed neck
- High arching palate
- Downward sloping eyes with ptosis
- Broad chest with widely spaced nipples
- Cubitus valgus
- Underdeveloped ovaries with reduced function
- Late or incomplete puberty
- Most women are infertile
Name some associated conditions with Turner’s syndrome
- Recurrent otitis media
- Recurrent urinary tract infections
- Coarctation of the aorta
- Hypothyroidism
- Hypertension
- Obesity
- Diabetes
- Osteoporosis
- Various specific learning disabilities
What are the 3 management options for Turner’s syndrome?
- Growth hormone therapy → prevent short stature
- Oestrogen + progesterone → establish female sex characteristics (regulate menstrual cycle + prevent osteoporosis)
- Fertility treatment → increase pregnancy chances
What gene loses it’s function causing Angelman syndrome?
UBE3A gene
(Specifically the copy inherited from the mother)
Deletion on chromosome 15
A child presents with widely spaced teeth, a happy demeanour and an unusual fascination with water. What is a possible underyling genetic condition?
Angelman syndrome
Name 4 features of Angelman syndrome
- 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
What is muscular dystrophy?
Umbrella term for genetic condition that causes the gradual weakening + wasting of muscles
What is Gower’s sign?
A specific technique used by children with proximal muscle weakness to stand up from the lying position
A 5 year old boy presents with vague symptoms of muscle weakness and you notice that they use their hands on the legs to help them stand up. What could be a possible underlying genetic condition?
Duchennes muscular dystrophy
What is the management for muscular dystrophy?
No cure
- Occupational therapy, physiotherapy, medical appliances (wheelchairs)
- Treatment of complications e.g. spinal scoliosis and heart failure
What type of inheritance underlies Duchennes muscular dystrophy?
X-linked recessive
(girls can be carriers)
What is the defective gene underlying Duchenne muscular dystrophy?
Dystrophin gene on the X-chromosone
(protein that helps hold muscles together)
If a mother is a carrier of Duchenne muscular dystrophy, what are the chances her child being a carrier or having the condition?
If the child is a:
- Girl → 50% carroer
- Boy → 50% having the condition
How do boys present with DMD?
- 3-5 years: Muscle weakness around pelvis
- Weakness = progressive
- Teenager: Wheelchair bound
- Life expectancy: 25-35 years with good management of cardiac + respiratory complications
What are the 2 management options for DMD?
- Oral steroids → slow muscle weakness progression
- Creatine → slight improvement in muscle strength
Which gene is affected in Beckers muscular dystrophy?
Dystrophin
(Very similar to Duchennes, but less severly affected and maintains some of its function)
(Management is similar Duchennes)
An adult presents with new:
- Progressive muscle weakness
- Prolonged muscle contractions
- Cataracts
- Cardiac arrhythmias
Possible underlying genetic condition?
Myotonic dystrophy
An adult patient tells you that he is unable to let go after shaking someones hand, and unable to release their grip on the doorknob after opening a door. What is a possible underlying genetic condition?
Myotonic dystrophy
A child is born with a flattened face, short neck, and upward palpebral fissures. On examination, they are hypotonic with a singular palmar crease bilaterally. During the pregnancy, the 20-week anomaly scan demonstrated a raised nuchal translucency. As the child ages, they are found to have mild to moderate learning difficulties. Possible diagnosis?
Down syndrome
Types of Down syndrome
- Trisomy 21: an extra copy of chromosome 21 in every cell - the most common form (95%)
- Mosaicism: an extra copy of chromosome 21 in some, but not all, cells (1%)
- Translocation: standard 46 chromosomes, however, chromosome 21 has an extra piece attached (4-5%)
Risk factors for Down syndrome
- Advancing maternal age: risk of Down syndrome in 40 year old mother is 1:100
- Carriers of the genetic translocation for Down syndrome
- Previous child with Down syndrome
Dysmorphic features of Down syndrome
- Hypotonia (reduced muscle tone)
- Brachycephaly (small head with a flat back)
- Short neck
- Short stature
- Flattened face and nose
- Prominent epicanthic folds
- Upward sloping palpebral fissures
- Single palmar crease
- Sandal toe gap (between 1st and 2nd toes)
Clinical features of Down syndrome
Symptoms:
* Developmental delay (gross motor delay, language delay, feeding difficulties)
* Cognitive (learning difficulties, autistic spectrum disorders)
* ENT (Recurrent otitis media, hearing loss: secondary to chronic infection)
* Gastrointestinal (constipation)
Signs:
* Facial features (brachycephaly, flat occiput, epicathal folds, upslanting palpebral fissures, short nose with low nasal bridge, small ears)
* Oral (small mouth, large, protruding tongue)
* Neck (short neck, excess skin posteriorly, neck pain)
* Hands (short hands, single palmar crease, fifth finger clinodactyly)
* Feet (sandal toe gap - between 1st and 2nd toes)
* Eyes (Brushfield spots - grey/white spots on the iris; congenital cataracts)
* Neurology (hypotonia)
* Gastrointestinal (duodenal or anal atresia or stenosis)
* Cardiovascular (heart murmur - AVSD most common)
What is the first line test for Down syndrome?
Combined test
(Perfomed at 11-14 weeks gestation)
Ultrasound: measure nuchal translucency (thickness of back of neck, over 6mm)
Maternal blood tests:
* Beta-human chorionic gonadotrophin (beta-HCG) (higher result = higher risk)
* Pregnancy-associated plasma protein-A (PAPPA) (lower result = higher risk
What does the triple test for Down syndrome involve?
Perform between 14-20 weeks gestation
Only maternal blood tests:
* Beta-HCG (higher result = greater risk)
* Alpha-fetoprotein (AFP) (lower result = greater risk)
* Serum oestriol (female sex hormone( (lower results = greater risk)
What does the quadruple test for Down syndrome involve?
The quadruple test is performed between 14 and 20 weeks gestation. It is identical to the triple test but also includes maternal blood for inhibin-A. A higher inhibin-A indicates a greater risk.
What are the antenatal tests for Down syndrome after the screening tests provide a risk score greater than 1 in 150?
The woman is offered amniocentesis or chorionic villus sampling. These tests involve taking a sample of the fetal cells, which then undergo karyotyping to give a definitive answer to whether the fetus is affected by Down’s or not.
- Chorionic villus sampling (CVS): biopsy of placental tissue (before 15 weeks gestation)
- Amniocentesis: aspiration of amniotic fluid (later in pregnancy)
Management of Down syndrome
“management would involve members of the multidisciplinary team”.
- Occupational therapy
- Speech and language therapy
- Physiotherapy
- Dietician
- Paediatrician
- GP
- Health visitors
- Cardiologist for congenital heart disease
- ENT specialist for ear problems
- Audiologist for hearing aids
- Optician for glasses
- Social services for social care and benefits
- Additional support with educational needs
- Charities such as the Down’s Syndrome Association
What are some routine follow up investigations that are important for children with Down syndrome
- Regular thyroid checks (2 yearly)
- Echocardiogram to diagnose cardiac defects
- Refular audiometry for hearing impairment
- Regular eye checks
Average life expectancy is 60 years
Complications of Down syndrome
- Congenital heart disease: AVSD, VSD, ASD
- Duodenal atresia: 30% of patients
- Short stature
- Haematological malignancy: higher rates of AML and ALL
- Alzheimer’s dementia : average age of onset 50-55 years
- Epilepsy : 8% of patients
- Obstructive sleep apnoea : estimated 30-60% of Down syndrome children
- Hearing loss: otitis media
- Obesity: reduced metabolic rates and hypothyroidism
- Hypothyroidism : up to 20% of patients
- Seborrheic dermatitis
- Coeliac disease
- Atlanto-axial instability
