Genomics in general practice

Disease specific topics

Developmental delay and intellectual disability

Developmental delay and intellectual disability


Children with features of developmental delay (DD) or intellectual disability (ID) should be referred to a paediatrician for a clinical genetics evaluation.

What do I need to know?

The causes of DD and ID can be genetic, non-genetic (eg fetal alcohol spectrum disorder, congenital infection) or unknown. Knowledge that DD and ID are caused by an underlying genetic condition may inform:

  • the ongoing management of the child’s condition
  • parents of future reproductive risk

There are several genetic causes of DD and ID:

  • Chromosomal
    • abnormalities of chromosome number (eg Down syndrome)
    • loss (ie deletion) or gain (ie duplication) of part of a chromosome 
  • Single-gene disorders
    • de novo gene variants A de novo variant is a new genetic variation that usually arises in the ova or sperm from which the individual is conceived (ie is not present in either parent). (occurring in the child but not inherited from a parent; eg Rett syndrome)
    • conditions that follow an autosomal dominant inheritance When a condition follows an autosomal dominant pattern of inheritance, the family tree will usually reveal multiple affected members in multiple generations on the same side of the family. Dominant conditions or traits are expressed when only a single gene variant is inherited. Wide variability in clinical expression is common in many autosomal dominant conditions, even within the same family. Early onset of conditions, such as cancer, can be indicative of autosomal dominant inheritance within a family. Not all dominant conditions show 100% penetrance eg BRCA1 gene mutations). pattern (eg tuberous sclerosis)
    • conditions that follow an autosomal recessive inheritance Autosomal recessive conditions affect either sex, and often occur in the absence of any family history. Recessive conditions or traits appear when an individual inherits two copies of pathogenic variants in the same gene (one from each parent). Parents of a child with an autosomal recessive condition are usually asymptomatic carriers. The affected child has two copies of the particular gene change. The recurrence risk of autosomal recessive conditions is one in four for each pregnancy. Wide variability in clinical expression is common in many autosomal recessive conditions. Autosomal recessive conditions are more common when the parents are consanguineous. pattern (eg Joubert syndrome)
    • conditions that follow an X-linked recessive inheritance Since a male inherits only one X chromosome (from his mother), when he has a pathogenic variant in a gene on the X-chromosome, he will have that condition. Males are usually more often and more severely affected because of X-inactivation in females. Since a male only passes his Y chromosome to his sons, there is no male-to-male transmission of X-linked conditions. With each pregnancy, females who are carriers of a pathogenic variant in a gene on the X-chromosome have a one-in-two chance of passing on the variant to each child. Sons who inherit the variant will be affected and daughters who inherit the variation will be carriers like their mothers. Daughters of affected males can only inherit the pathogenic variant from their father and are known as ‘obligate carriers’. pattern (eg fragile X syndrome [FXS])

Genetic testing

Chromosome microarray (CMA) is now considered a first-line genetic test for the investigation of DD, ID, autism spectrum disorder (ASD), and congenital abnormalities. CMA does not detect gene variants Gene variants are small DNA sequence changes (ie additions, duplications, deletions, substitutions). These variants can have a range of effects: some may cause disease (pathogenic variant), while others do not cause disease but may modify an individual’s risk of disease (i.e may increase risk or provide a protective effect). The vast majority of gene variants are benign and do not result in disease but rather contribute to the differences between people. causing FXS (ie FMR1 gene), so an additional DNA test for diagnosis of FXS must be ordered alongside.

While general practitioners (GPs) are able to order CMAs, many choose not to, given the complex interpretation of the results. However, ordering CMA and FXS tests in parallel with referral to a paediatrician can reduce waiting times for patients.

A Medicare Benefits Schedule (MBS) rebate is available for CMA in situations where the patient has DD, ID, ASD or at least two congenital abnormalities. DNA testing for FXS is available with an MBS rebate when the patient:

  • exhibits ID, ataxia, neurodegeneration, or primary ovarian insufficiency consistent with an FMR1 mutation
  • has a relative with an FMR1 mutation

When should I refer?

A genetic cause should be suspected in individuals with DD or any of the following:

  • dysmorphic features
  • motor weakness and delayed motor milestones
  • autistic features
  • epilepsy
  • congenital anomalies (eg cleft palate, heart defects)
  • a family history of autism, FXS or other developmental/learning disability

Patients with these features should be referred to a paediatrician.

Urgent referral to a paediatric neurologist is recommended if an infant or child with motor weakness and delay in the setting of normal cognition (eg suspected spinal muscular atrophy or muscular dystrophy). Delays in referral may delay access to new drug treatment for spinal muscular atrophy.

Further reading

  • The Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice. 9th edn. Melbourne: RACGP, 2016. [Accessed 6 September 2022].
  • Canadian Task Force on Preventive Health Care. Recommendations on screening for developmental delay. CMAJ May 17, 2016 188 (8) 579-587
  • Miller DT, Adam MP, Aradhya S, et al. Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86(5):749–64.
  • Department of Health. Medicare Benefits Schedule (MBS) Online. Canberra: DoH, 2022. [Accessed 11 February 2022].
  • The Royal Australian College of General Practitioners. Beware the rare
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