Genetics and syndromes 2 Flashcards
What are the clinical features of foetal alcohol syndrome?
o Growth restriction o Characteristic face Saddle-shaped nose Maxillary hypoplasia Absent philtrum Short, thin upper lip o Developmental delay- reduced IQ o Microcephaly o Cerebral palsy o Cardiac defects- up 70% o ADHD or autisim-like behaviour
What is fragile X syndrome?
Commonest familial form of learning difficulties
X-linked recessive disorder
• Genes with the full mutation contain more than 200 copies of the repeat sequence- affecting gene function causing all the clinical features
What are the clinical features of fragile X syndrome?
o Moderate-severe learning difficulties- IQ 20-80
o Macrocephaly
o Macro-orchidism- post-pubertal
Characteristic facies- long face, large everted ears, prominent mandible, broad forehead
o Other features-mitral valve prolapse, joint laxity, scoliosis, autisim, hyperactivity
What is Marfan syndrome?
1 in 5000
Variable autosomal dominant multisystem disorder caused by mutation in the FBN1 gene of chromosome 15q- there is a high new mutation rate (30%)
What are the clinical features of Marfan syndrome?
o Tall & slim body build with long legs o Pectus malformation of the sternum o Scoliosis o High narrow palate o Long fingers- arachnodactyly o Joint laxity o Myopic- may develop lens dislocation • Cardiac features- floppy mitral valve, but with time there may be dilation of the aortic root leading to to ascending aorta aneurysm and aortic dissection treatment with Losartan has greatly improved the outlook in terms of stabilizing aneurysms
What is Rett syndrome?
1 in 10000 female births
caused by a mutation in the MECP2 gene on Xq28
• Girls with Rett’s syndrome appear normal in first 6 months of life
• It is a severe neurodevelopement disorder- almost exclusively affects girls and presents after 1y/o with development regression and loss or purposeful hand movements
• May develop seizures, scoliosis, erratic breathing with episodes of breath-holding & hyperventiliation and stereotypic hand-wringing
What is stage 1 of Rett syndrome?
Development slows down or stops altogether during the period from 6-18 months
o Hypotonia
o Difficulty feeding
o Unusual, repetitive hand movements or jerky limb movements
o Delay with development of speech
o Mobility problems- such as problems sitting, crawling and walking
o Lack of interest in toys
What is stage 2 of Rett syndrome?
Regression- starts to lose some abilities during the ages of 1-4yrs
o Loss of the ability to use the hands purposefully – repetitive hand movements are often difficult to control and include wringing, washing, clapping or tapping
o Periods of distress, irritability and sometimes screaming for no obvious reason
o Social withdrawal – a loss of interest in people and avoidance of eye contact
o Unsteadiness and awkwardness when walking
o Problems sleeping
o Slowing of head growth
o Difficulty eating, chewing or swallowing, and sometimes constipation that may cause tummy aches
What is stage 3 of Rett syndrome?
Plateau- can begin between 2-10yr and may get slightly better with improvements in behaviour, interest in people & surroundings and improvements in alertness, attention & communication
o Seizures may become more common
o Irregular breathing patterns may get worse
o Teeth grinding
o Arrhythmias
What is stage 4 of Rett syndrome?
Deterioration in Movement- can last for years or decades, but communication, language & brain function do not tend to get any worse o Development of a scoliosis o Muscle weakness and spasticity o Losing the ability to walk o Seizures become less of a problem
What is Duchenne muscular dystrophy?
X-linked recessive disorder
although about 1/3 have new mutations- it results from a deletion on the short arm of the X chromosome at the Xp21 site
• Affects all men and women who are homozygous
Dystophin is deficient- several aberrant intracellular signaling pathways associated an influx of Ca2+ ions, a breakdown of the calcium calmodulin complex and excess of free radicals leading to myofibre necrosis
What are the clinical features of Duchenne muscular dystrophy?
Late walking and speech delay
• In early phase of the disease- boys have difficulty rising from the floor
Gower’s manoeuvre sign where
the child climbs up high thighs with his hands to get up off the floor
• Later there is early loss of ambulation (mean age 9yrs)- also slower and clumsier than peers
• Affected boys develop a progressive cardiomyopathy
• 30% of boys with DMD have a mild learning disability that is not progressive
Mount stairs one by one
• Average age for diagnosis is 5.5yrs- but children often become symptomatic much earlier
What are the other signs in Duchenne muscular dystrophy?
o Waddling lordotic gait
o Calf pseudohypertrophy- replacement of muscle fibres by fat & fibrous tissue
o Weakness in limb girdles- Gower’s sign
o Sparing of the facial, extra-ocular and bulbar muscles
o Language delay
o Scoliosis
What are the screening tests for Duchenne muscular dystrophy?
- Serum creatinine phosphokinase (CPK) is markedly elevated- this can be detected by a neonatal screening test
- Serum CK is also grossly elevated- usually >10 times normal levels, diagnosis is often possible by genetic testing, avoiding the need for muscle biopsy
- Genetic analysis cannot differentiate between the milder Becker MD and more severe DMD- therefore expert interpretation is required
What is the management for Duchenne muscular dystrophy?
Exercise to maintain muscle power and mobility
Stretching and provision of night splints- to prevent contracture of the ankles
Orthoses to prolong walking
Lengthening of Achilles tendon
Maintaining a good sitting posture (truncal brace, moulded seat, surgical insertion of a metal spinal rod)
CPAP for nocturnal hypoxia
Corticosteroids to preserve mobility and prevent scoliosis- prednisolone for 10 days each month
