Central Hypotonia ✅ Flashcards
What do you need to distinguish between when assessing hypotonia?
- Central hypotonia
- Generalised hypotonia and weakness
- Peripheral hypotonia
Where does central hypotonia affect?
Predominantly head and trunk
Where does generalised hypotonia and weakness affect?
All aspects
Where does peripheral hypotonia affect?
Predominantly th elimbs
When does moderate to severe central hypotonia tend to be identified?
In the neonatal period
How might moderate to severe central hypotonia present in the neonatal period?
- Respiratory difficulties
- Feeding difficulties
- ‘Floppy baby’
What investigations may be done in an infant with central hypotonia?
- Microbiological tests
- Neuroimaging
- Blood ammonia and lactate levels
- Plasma and urine amino acids and urine organic acids
- Very long chain fatty acids
- Microarray-based comparative genomic hybridisation
When are microbiological tests done in central hypotonia?
If presenting in neonatal period
Why are microbiological tests done in central hypotonia presenting in the neonatal period?
Rule out sepsis
What are blood ammonia and lactate levels done in central hypotonia?
Look for inborn errors of metabolism
Why are plasma and urine amino acids and urine organic acids done in central hypotonia?
Look for organic acidaemias
Why are very long chain fatty acids checked in central hypotonia?
Look for peroxisomal disorders
What specific disorder types should be considered in central hypotonia?
- Aneuploidy
- Single gene disorders
- Metabolic disorders
- Structural disorders
Give an example of an aneuploidy disorder than can cause central hypotonia?
Down’s syndrome,
Give an example of a single gene disorder that can cause central hypotonia?
Prader-Willi syndrome
Give an example of a metabolic disorder that can cause central hypotonia?
Peroxisomal diosrders
Give an example of a structural disorder that can cause central hypotonia?
Structural brain malformations
What causes Down’s syndrome?
Additional copy of chromosome 21
What are the potential mechanisms behind the additional chromosome 21 in Down’s syndrome?
- Non-disjunction (most common)
- Unbalanced translocation
- Mosaicism
What are the clinical features of Down’s syndrome?
- Typical dysmorphic features
- Central hypotonia
- Delay in all developmental milestones
- Initial feeding difficulties
- Associated congenital anomalies, including heart defects
In what % of children with Down’s syndrome are there associated congenital anomalies?
50%
What happens to the hypotonia in a child with Down’s syndrome with age?
In some, disappears as child develops, but many stay ‘floppy’. Studies have shown that infantile floppiness does improve over time, but often remain with some degree of hypotonia
What is the result of continued hypotonia in a child with Down’s syndrome?
Responsible for much of their delay in motor milestones and impaired motor function
Why is the belief that the floppiness of children with Down’s syndrome is responsible for their motor delay disputed?
Recent studies have shown that hypotonia is seen when children and adults with Down’s syndrome are not moving, and therefore it doesn’t actually impair coordinated movement
What does the fact that in Down’s syndrome, the muscles are floppy at rest suggest?
There may be some peripheral component to the observed hypotonia
What is Prader-Willi syndrome caused by?
- Deletion on long arm of paternally inherited chromosome (15q13) (70%)
- Maternal uniparental disomy (25%)
- Imprinting defect (5%)
Which form of Prader-Willi syndrome carries an increased risk for future pregnancies?
When caused by imprinting defect
Which babeis should Prader-Willi syndrome be considered in?
- Feeding difficulties
- Needing NG tube feeding
- Sticky saliva
- Extreme hypokinesia
- Combination of central hypotonia and limb dystonia
How can children with Prader-Willi syndrome be diagnosed visually?
They have distinctive facial characteristics and other dysmorphic features
What happens to feeding in children with Prader-Willi syndrome as they grow?
They begin to show increased appetite
What can the increased appetite as children with Prader-Willi syndrome grow lead to?
Excessive eating (hyperphagia) and life-threatening obesity
What other problems do older children with Prader-Willi syndrome have?
- Hypogonadism
- Learning disabilities, can be severe
What does hypogonadism in Prader-Willi syndrome lead to?
Immature development of sexual organs and delay in puberty
In what developmental domains do children with Prader-Willi syndrome tend to be particularly impaired?
Emotional and social development
What are peroxisomes?
Spherical organelles within cells containing important oxidative and other enzymes
How do babies with peroxisomal disorders tend to present?
Extreme hypotonia of neck in context of general neonatal hypotonia
What can peroxisomal disorders be divided into?
- Global peroxisomal disorders
- Adenoleukodystrophy
What happens in global peroxisomal disorders?
Few or no peroxisomes are generated, or there are single peroxisomal enzyme defects that induce a similar phenotype
What is adenoleukodystrophy?
An X-linked inherited condition caused by a defect in the gene that codes for one of the ATP-binding transporters within the cell
What blood test might detect peroxisomal disoders?
Measurement of very long chain fatty acids
Is there a metabolic screen that can detect all cases of peroxisomal disorders?
No
What must happen when interpreting results of metabolic tests?
They must be correlated with clinical findings
What clinical features might be present with peroxisomal disorders?
- Neonatal seizures
- Retinal blindness
- Sensorineural deafness
- Dysmorphic features in specific syndromes
- Hepatomegaly
- Leukodystrophy
- Neuronal migration defects
What is retinal blindness also known as?
Leber amaurosis
When should peroxisomal disorders be suspected in older children?
- School age boy showing developmental regression with previously normal development
- Older girls with spastic paraplegia
What needs to be ensured when a child presents with hypotonia due to a brain malformation?
That the malformation is not caused by a metabolic disorder, which may require specific management
