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?
what chromosome asc with?
- Learning disability
- Congenital heart disease
- Hypothyroidism
- Immunity
- Early onset Alzheimer disease
Trisomy 21
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 and the gene responsible
- 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
How can we test thousands of genes and find the cause of the disability?
Whole-Exome Sequencingof Germline DNA
what is a glut1 deficiency?
treatment?
SLC2A1 deletion or mutation
Treatment with ketogenic diet
why is phenotypic important?
The key to assessment of clinical relevance is the phenotype
That’s why accurate description of clinical features is important
A diagnosis helps the family see the future
And can help with future pregnancy planning, clinical care and treatment
