Genetics Flashcards
What is the role of paediatric genetics?
- Diagnosis in congenital malformations and learning disability
- Approach to dysmorphic child
- Investigation into developmental delay
What conditions is Down syndrome associated with?
- Learning disability
- Congenital heart disease
- Hypothyroidism
- Immunity
- Early onset Alzheimer disease
What ethical issues are there surrounding testing for Down syndrome?
- Regarded as standard care in Western world
- Non-invasive testing will soon be available
- Is a world without Down syndrome acceptable?
- Screening leads to termination
What does congenital mean?
- Present at birth
- Can be genetic, environmental or both
What are the causes of multiple congenital anomaly syndromes?
- 55% unknown
- 30% single gene disorders
- 10% chromosomal
- 5% teratogens
What is the epidemiology of congenital anomalies/
- 3% all births
- 20% children’s hospital admissions
- 30% infant deaths
Syndrome
A distinct group of symptoms and signs which associated together for a characteristic clinicl picture or entitiy
How common are multiple congenital anomalies?
- Individually rare
- Common as a group
How do you diagnose a rare intellectual disability or malformation syndrome?
- History
- Description
- Recognition of patterns
- Testing
What testing can be performed in diagnosis of a rare intellectual disability or malformation syndrome?
- Microarray standard
- Targeted testing
- Moving to exome and genome
What should be looked at when describing a dysmorphic child?
- Position and shape of facial features
- Hands
- Growth of child
- General features
What should be looked at regarding the head of a dysmorphic child?
- Shape
- Size: macrocephaly, microcephaly
- Ear position
What type of ears suggest lack of maturity?
Low-set, posteriorly rotated
What should be looked at regarding the eyes in a dysmorphic child?
Hypertelorism
-Inner canthal distance ICD and inter-pupillary distance IPD increased
Telecanthus / epicanthic folds
-ICD increased
What hand measurements should be taken when examining a dysmorphic child?
- Finger length
- Digital abnormalities
- Palmar creases
Give examples of syndromes which can affect the hands.
- Marfan syndrome
- Down syndrome
How are the hands affected in Marfan’s syndrome?
Middle finger length divided by the total hand length is >44%
How can malformation present?
Alone or part of a syndrome
Give examples of malformation.
- Polysyndactylty alone (Hox D13 one cause)
- Acrocephalopolysyndatyly (Greig / GLI3)
How does acrocephalopolysyndactyly present?
- Tall forehead
- Polydactyly
- Syndactyly
Sequence
One abnormality leads to another and can have multiple causes
What is Pierre-Robin sequence?
Small chin which leads to cleft palate
What are the features of foetal akinesia sequence?
- Reduced foetal movements
- Reduced breathing
- Contractures
- Clefting
- Lung hypoplasia
What are deformation and disruption?
Pattern of development normal to start with but becomes abnormal
Deformation: Organ parts are there
Disruption: Parts of organ / body part absent
Association
2 features or more that occur together more often than expected by chance though the mechanism is unclear
Give an examples of association.
VATER association
- Vertebral anomalies
- Ano-rectal atresia
- Tracheo-oesphageal fistula
- Radial anomalies
What is the genetics behind Turner syndrome?
45, X
How does Turner syndrome present?
- Lymphoedema (Puffy feet, nuchal translucency / cystic hygroma)
- Increased carrying angle, low hairline, wide spaced nipples, sandal gap
- Short stature, occ. v mild learning difficulties
- Coarctation of aorta, hypothyroidism, UTI, osteoporosis & hypertension
- Primary amenorrhoea & infertility
How can some features of Turner syndrome be mitigated?
Hormone therapy
How is learning disability investigated genetically?
- Microarray
- Fragile X
- Targeted tests driven by phenotype
What are the features of 22q11 deletion syndrome?
- Cleft palate
- Abnormal facies
- Thymic hypoplasia / immune deficiency
- Calcium
- Heart problems
What genetic variations are common?
- Copy number variants
- Sequence variation
