Paediatrics & Child Health: Genetic and Metabolic Medicine

Presentations

• Deafness

Conditions

• Cardiomyopathy and genetic cardiac arrhythmia
• Cystic fibrosis
• Duchenne muscular dystrophy (DMD)
• Fragile X syndrome (FXS)
• Genetic malignancies, such as retinoblastoma and Wilms tumour
• Klinefelter syndrome
• Marfan syndrome
• Microarray abnormalities:
  
  • 1q21.1 deletion or duplication
  • 15q11.2 deletion
  • 16p11.2 deletion or duplication
  • 22q11.2 deletion or duplication
• Myotonic dystrophy
• Neurofibromatosis type 1 (NF1)
• Noonan syndrome (NS)
• Osteogenesis imperfecta (OI)
• Trisomy 21
• Turner syndrome

For each presentation and condition, Basic Trainees will know how to:

Synthesise

• recognise the clinical presentation
• identify relevant epidemiology, pathophysiology, and clinical science
• take a relevant clinical history
• conduct an appropriate examination
• establish a differential diagnosis
• plan and arrange appropriate investigations
• consider the impact of illness and disease on patients¹ and their quality of life

Manage

• provide evidence-based management
  For less common or more complex presentations and conditions the trainee must also seek expert opinions
• prescribe therapies tailored to patients’ needs and conditions
• recognise potential complications of disease and its management, and initiate preventative strategies
• involve multidisciplinary teams

Consider other factors

• identify individual and social factors and the impact of these on diagnosis and management

Conditions

• Alagille syndrome
• Alpha-1 antitrypsin deficiency
• Disorders of chromosomal duplication or deletion, such as cri-du-chat syndrome
• Familial and genetic malignancies
• Genetic aspects of endocrine disorders:
  
  • congenital adrenal hyperplasia
  • congenital hypothyroidism
• Genetic aspects of haematological disorders:
  
  • G6PD deficiency
  • haemochromatosis
  • haemophilia
  • sickle cell disease
  • thalassaemia
• Genetic aspects of neurological disorders:
  
  • ataxia telangiectasia
  • Charcot–Marie–Tooth disease
  • Huntington disease
  • Rett syndrome
  • tuberous sclerosis
• Genetic disorders of growth and musculoskeletal development:
  • achondroplasia
  • Treacher Collins syndrome
• Genetic imprinting disorders:
  
  • Angelman syndrome
  • Beckwith–Wiedemann syndrome
  • Prader–Willi syndrome
• Storage disorders:
  
  • Gaucher disease
  • Wilson disease
• Mitochondrial disorders
• Mucopolysaccharidoses
• Ring chromosome disorders
• Substrate metabolism disorders:
  
  • amino acid metabolism defects:
    
    • aspartic acid (Canavan disease)
    • cysteine
    • glutamic acid
    • glycine
    • lysine
    • methionine
    • phenylalanine
    • proline
    • tryptophan
    • tyrosine
    • valine / leucine / isoleucine
  • carbohydrate metabolism defects:
    
    • defects in fructose metabolism
    • defects in galactose metabolism
    • defects in intermediary carbohydrate metabolism with lactic acidosis
    • glycogen storage diseases
  • lipid metabolism defects, such as:
    
    • lipidosis (lysosomal storage disease)
    • lipoprotein metabolism disorders
    • mitochondrial fatty acid oxidation disorders
    • very long chain fatty acids disorders
• Trisomy 13 and 18
• Williams syndrome

For each presentation and condition, Basic Trainees will know how to:

Synthesise

• recognise the clinical presentation
• identify relevant epidemiology, pathophysiology, and clinical science
• take a relevant clinical history
• conduct an appropriate examination
• establish a differential diagnosis
• plan and arrange appropriate investigations
• consider the impact of illness and disease on patients¹ and their quality of life

Manage

• provide evidence-based management
  For less common or more complex presentations and conditions the trainee must also seek expert opinions
• prescribe therapies tailored to patients’ needs and conditions
• recognise potential complications of disease and its management, and initiate preventative strategies
• involve multidisciplinary teams

Consider other factors

• identify individual and social factors and the impact of these on diagnosis and management

• Basic principles of pharmacogenetics and individualised medicine
• Definitions of polymorphism, mutation, genetic segregation analysis, and sex-linked, multifactorial, and polygenic inheritance
• Dietary therapy in inborn errors of metabolism (IEMs)
• Enzyme replacement therapy and substrate inhibition therapy
• Genetic testing techniques, such as:
  
  • exome and genome sequencing
  • fluorescence in-situ hybridisation (FISH)
  • gene sequencing
  • polymerase chain reaction (PCR)
• Principles of classical Mendelian and population genetics, sex-linked,
  mitochondrial inheritance, uniparental disomy, and repeating triplet
  sequences
• Principles of major cancer genetics
• Structure and function of human cells, genes, DNA, RNA, and proteins
• Use of co-factors in IEMs

Investigations

• Conventional karyotype
• Cystic fibrosis mutation testing
• Exome and genome sequencing
• FISH probes
• Metabolic screening tests
• Molecular karyotype
• Neonatal screening
• Single gene testing for conditions such as cystic fibrosis, dystrophin, and fragile X syndrome (FXS)
• Skeletal survey
• Skin biopsy

Clinical assessment tools

• Clinical photography
• Dysmorphic feature description
• Specialised growth charts

• Appropriate referral to clinical genetics services, including referral for
  prenatal testing, carrier testing, and preimplantation genetic diagnosis
• Documenting family histories on genograms and determining modes of
  inheritance
• Ethical implications when using clinical photography
• Genetic underpinning of neurological disorders:
  
  • genetic causes of neurological conditions, such as Dravet
    syndrome, DMD, and spinal muscular atrophy

  • role of genetic testing technologies in diagnosis of neurological
    disease (basic understanding):

    • array-based comparative genomic hybridisation (CGH array)
    • gene panel testing
    • individual gene testing
    • whole exome testing
    • whole genome testing
• Goals and potential benefits of the Human Genome Project (HGP)
• Legal and ethical principles of genetic testing, such as:
  
  • ethical barriers to testing minors for adult onset conditions
  • ethics consultation
  • familial implications of a genetic diagnosis, including discussion of autosomal recessive, autosomal dominant, and X-linked inheritance
  • need for and process of obtaining written consent
  • predictive testing processes
• Patient and family counselling regarding findings of variants of uncertain significance (VOUS) and incidental findings in genetic testing, such as:
  
  • absence of prognostic information
  • need for family studies
  • possibility of functional studies
• Prenatal options for:
  
  • first trimester screening, including nuchal translucency and noninvasive prenatal testing
  • fetal gender determination
  • fetal mutation testing
  • non testing
  • parental testing
  • preimplantation genetic diagnosis
• Recognition of clinical features suggestive of an underlying genetic condition or syndromic diagnosis
• VOUS, reduced penetrance, and attenuated phenotype