Syndromes Flashcards
Down’s Syndrome
- Understand the cytogenetics and obstetric risk factors for down syndrome
- List the clinical features and associated problems of down syndrome.
- Outline the diagnostic investigations for down syndrome.
- Outline the long term problems associated with down syndrome and the multi-disciplinary nature of care.
Cytogenetics: Trisomy 21
94% of cases are due to nondisjunction of the chromosomes durign meiosis, 5% are due to translocation and the remaining 1% due to mosaicism
Obstetric risk factors:
- Increased maternal age
- Previous infant with Down syndrome
- Parental translocation/carrier parent
Clinical features:
Craniofacial abnormalities
- Flat occiput
- Flat nose
- Epicanthic folds and upslanting palpebrae fissures
- Small ears
- Small mouth and protruding tongue
Other abnormalities
- Single palmar crease
- Enlarged ‘sandal-gap’
- Short neck
- Hypotonicity
- Cogenital cardiac defects
- Duodenal atresia
Associated problems:
Cardiac defects
Intellectual disability
Early onset dementia
Short stature
Increased susceptibility to infections
Hearing loss, due to secretory otitis media
Vision impairment, due to cataracts/myopia/strabismus
Increased susceptibility to hypothyroidism and coeliac disease
Diagnostic investigations:
10 - 14 weeks gestation - Combined test
- Nuchal translucency (increased)
- Beta-hCG (↑) and PAPP-A (↓)
14 - 20 weeks gestation
- AFP and unconjugated oestriol (↓)
- Beta-hCG and inhibin A (↑)
Those whose risk if classified as high may then have CVS (11-14 weeks) or amniocentesis (15-18 weeks) performed to allow confirmation of diagnosis.
Associated long term problems:
- Heart defects
- Intellectual disability
- Reduced motor development
- Increased susceptibility to infections
- Hearing impairment, from secretory otitis media
- Visual impairment, from cataracts/strabismus/myopia
- Increased risk of hypothyroidism and coeliac disease
- Early onset Alzheimer’s
Turner’s syndrome
- Understand the cytogenetics of turner syndrome
- List the clinical features and associated problems of turner syndrome.
- Outline the diagnostic investigations for turner syndrome.
- Outline the long term problems and management options for turner syndrome
Cytogenetics
Absence of an X chromosome in females, leading to 45 XO
May see complete absence of a chromosome or partial loss
Generally sporadic but for individuals with a short p-arm the syndrome is inherited.
Clinical features
- Oedema of the hands and feet in the neonatal period (may persist)
- Short stature
- Webbed neck
- Widely spaced nipples and ‘shield-chest’
- Cubital valgus
- Spoon shaped nails (under developed)
- Recurrent otitis media
- Congenital cardiac defects - CoA, bicuspid aortic valve, hypoplastic left heart syndrome
- Renal abnormalities
- Absence of secondary sexual characteristics
Associated problems
- Reduced life expectancy
- Renal problems
- Hearing loss (due to recurrent infections)
- Infertility (due to ovarian agenesis)
- Osteoporosis
- Cardiovascular disease
- Hypertension
- Hypothyroidism
Diagnostic investigations
- Detection via antenatal scans:
- Cystic hygroma*
- Congenital heart or renal defects
- None immune foetal hydrops
- Karotyping
- Serum LH and FSH: Low between the ages of 4-10, elevated after age 10
Long term problems
SEE ABOVE
Management options
- Monitoring: TFTs, U&Es, hearing
- Sex hormone replacement: To allow for adequate growth
- Oestrogen replacement therapy: To allow for the development of secondary sexual characteristics, does NOT allow for fertility
- IVF and egg donation to allow for conception
* Cystic hygroma: Describes a fluid filled sac, resultant of failed lymphatic drainage. Commonly seen on the back of the head or neck but may occur anywhere on the body
Understand the importance of genetic counselling in paediatrics.
Describe some common dysmorphic features associated with syndromes.
Genetic counselling: Discussing the risk of a genetic condition and the results of genetic screening.
Common dysmorphic features:
- Low set ears
- Epicanthic folds
Understand the aetiology, key features and neurodevelopmental problems of foetal alcohol syndrome.
Aetiology:
Alcohol consumption during pregnancy - any trimester
Higher levels of consumption and greater frequency of consumption is associated with increased risk of development of FAS
There is no safe level of consumption of pregnancy therefore abstinence is advised.
Key features:
- IUGR
- Facies:
- Hypertelorism, with small eyes
- Smooth philtrum
- Short, thin upper lip
- Microcephaly
- Saddle shaped nose
- Developmental delay
- Cardiac abnormalities: ASD, VSD, TOF
Neurodevelopmental problems:
- FAS disrupts normal neurolodevelopment
- Manifests as delayed achievement of developmental milestones
- Problems with speech, language, learning and behaviour
- Poor academic performance and social skills may be seen in adolescents
Be aware of fragile X syndrome and the risk of learning difficulties.
Fragile X syndrome: An X-linked disorder, therefore seen in males - with females acting as carriers.
A trinucelotide repeat disorder (CGG). ?Leads to breakage of the q-arm on the X chromosome
Clinical features
- Characteristic facies: Broad forehead, large everted ears, elongated face, prominent mandible
- Macrocephaly
- Intellectual disability
- Autism
- Scoliosis
- Hyperactivity
- Macro-orchidism
- Mitral valve prolapse
- Stereotypical hand movements
Know the clinical features and later risks associated with Marfan syndrome
An autosomal dominant disorder of connective tissue, in which there is loss of elastic tissue.
Clinical features:
- Tall, thin body with long limbs
- Pectus malformation (excavatum or carinatum)
- Scoliosis
- High narrow palate
- Arachnodactyly
- Joint laxity
- Myopia and lens dislocation
- Floppy mitral valve
- Aortic root dilation
Risks associated with Marfan syndrome
- Dilation of the aortic root, leading to aortic aneurysm/dissection
Appreciate the presenting features and development regression seen in Rett’s syndrome.
Mainly affects females. Defect in a gene responsibile for neurological development
Clinical features
- Appear to be developing normally until around 6 months of age
- Usually presents after 1 year of age
- Developmental regression
- Loss of purposeful movements
- Characteristic hand wringing seen
- Seizures
- Erratic breathing: Periods of breath holding and hyperventiliation
- Scoliosis
Duchenne Muscular Dystrophy:
- Understand the mode of inheritance. (gender)
- Describe the clinical features.
- Outline the early diagnostic signs/symptoms and initial screening tests.
- Be aware of the management of cases from time of diagnosis.
Mode of inheritance
X-linked recessive condition - therefore, affects males
May arise from de novo mutations
Mutations in the dystrophin gene ultimately lead to myofiber necrosis
Clinical features
Developmental delay (particularly walking and speaking) at around 5 years of age - NOT regression
EARLY STAGES OF THE DISEASE
- Gower’s manoeuvre sign
- Waddling gait
- Slow/clumsier than peers
- Mount stairs one by one
- Run slowl compared to peers
LATE STAGES OF THE DISEASE
- Loss of ambulation (~9 years)
- Progressive cardiomyopathy
- Non-progressive learning disability
Early diagnostic signs/symptoms
Consider DMD in any male who is not walking by 18 months and has delayed motor development or global developmental delay.
Symptoms typically appear between 1 - 3 years of age, with DMD causing these children to appear slower than their peers and experience difficulty walking, running and climbing the stairs.
Signs:
- Hypotonia and hyporeflexia on neurological examination
- Flexor and plantarflexor strength > extensor and dorsiflexor strength on MSK examination
- Musculotendinous contractions - lumbar lordosis and heels
- Calf pseudohypertrophy*
Symptoms:
- Difficulty walking and recurrent falls
- Difficulty focusing attention/hyperactivity
- Incontinence
- Delayed development
Initial screening tests
↑ Serum creatinine kinase
Genetic testing - Xp
Electromyogram and muscle biiopsy may be considered
Management
The main aim of treatment is maximising the time the patient is able to ambulate.
Stage 1, ambulatory patient: Psychological support, prevention of contractures, preservation of muscle strength using glucocorticoids
Stage 2, non-ambulant patient: Maintenance of optimal nutrition and activities of daily living. Prevention of scoliosis
Stage 3, ventilator supported patient: Inspiratory and expiratory muscle rest and support
By the age of 12 most patients are wheelchair bound.
Adolescence sees weakening of the respiratory muscles and weakening of the cough mechanism, leading to recurrent infections.
Cardiomyopathy typically develops my the age of 18.
Life expectancy is reduced to ~ 30 years.
*Calf pseudohypertrophy: Muscle is replaced by adipose and fibrous tissue
Neurofibromatosis
(a neurocutaneous syndrome)
- Outline the diagnostic criteria and types.
- Be aware of the clinical features and presentation.
- Be aware of the long term health problems.
An autosomal dominant condition with causes the growth of tumours on nerve cells.
Types
NF1 and NF2 are genetically and clinically distinct conditions but do have some clinical overlap.
NF1: Mutation on chromosome 17. More common.
NF2: Mutation on chromosome 22.
Diagnostic criteria
SEE TABLE
Clinical features
Features may be present at birth but presentation can be delayed.
- Megalencephaly
- Learning difficulties
- Epilepsy
NF-2: Bilateral acoustic neuromata presentign with deafness and, in some cases, cerebellopontin angle syndrome with CN VII paralysis and cerebellar ataxia.
Presentation
NF-1: Cutaneous features become more evident after puberty
NF-2: Usually presents in adolescence
Long term health problems
- Pulmonary hypertension
- Renal artery stenosis
- Hypertension may develop secondary to this
- Neurological signs if neurofibromata growth occurs within a bony foramen
- Intrusion of tumours into the orbital cavity, brain and nerves
- Cranial nerve palsies (via neurofibromatoma growth)
- Malignant transformation of neurofibromas (→ sarcomatous change)
- Association with endocrinological disorders (MEN)
Tuberous Sclerosis
(a neurocutaneous syndrome)
- Outline the diagnostic criteria and types.
- Be aware of the clinical features and presentation.
- Be aware of the long term health problems.
Autosomal dominant. Up to 70% of mutations arise de novo.
Types
TSC1 gene mutation
TSC2 gene mutation: More common and associated with increased severity of disease.
Diagnostic criteria
Cutaneous features:
- Depigmented ‘asf leaf’ shaped patches or amelanotic naevi which fluoresce under ultraviolet light (Wood’s light)
- Shagreen patches (roughened patches of skin), usually over the lumbar spine
- Angiofibromata in butterfly distribution - unusual before 3 years old
Neurological features (seen in 50%):
- Infantile spasms (hypsarrhythmia on EEG) and developmental delay
- Epilepsy
- Intellectual disability, often with autism
Other features:
- Fibromata beneath the nails (subungual fibromata)
- Dense white areas on the retina (phakomata) from local degeneration
- Rhabdomyomata of the heart (usually resolve in infancy)
- Angiomyolipomas and polycystic kidneys
- Cysts in the lungs
- Cerebral subependymal nodules and cortical tubules (always present, even if asymptomatic)
- Subependymal nodules → enlargement → block flow of CSF → headache, vomiting and hydrocephalus
Clinical features
SEE FEATURES ABOVE
Presentation
May be detected antenatally.
Typically presents with childhood - skin changes and epilepsy before the age of 5.
CT or MRI scanning reveal calcified subependymal nodules and tubules from age 2.
Long term health problems
- Epilepsy
- Cardiac symptoms
- Renal complications: Hypertension, reduced renal function
- Skin lesions
- Pulmonary complications
- Intellectual disabilty
- Behavioural difficulties
Achondroplasia: Be able to outline the clinical features and long term problems.
Clinical features:
- Short stature
- Large head
- Frontal bossing
- Flattening of the nasal bridge
- Short, broad hands (brachydactyly)
- Marked lumbar lordosis
- Hydrocephalus (in some cases)
Long term problems:
- Failure to thrive, due to chronic hypoxaemia
- Cervicomedullary compression (can lead to respiratory difficulties, feeding problems and hypotonia)
- Lordosis, with subsequent back pain causing difficulty walking
PKU: Briefly outline the diagnosis and management of Phenylketonuria
Diagnosis: Detected on newborn heelprick test
Management
- Restriction of dietary protein/phenylalanine
- Supplementation of other dietary proteins
- Phe-free formula milk for infants with supplementation of daily Phe requirements through addition of breast or normal formula milk
Sturge-Weber Syndrome
Clinical features
Clinical features
- Haemangiomatous facial lesion (port wine stain) in the distribution of the trigeminal nerve (ophthalmic)
- Similar intracranial lesion is seen
- Epilepsy
- Intellectual disability
- Contralateral hemiplegia
- High risk of ipsilateral glaucoma
