Neurodevelopmental Disorders Genetics Clinic

We offer genetic assessments for individuals with neurodevelopmental disorders (NDDs), including global developmental delay, intellectual disability and autism. We provide interpretation of genetic test results, additional genetic testing (where indicated), and genetic counselling for patients and their families.

As of January 1st 2024: First-tier genetic testing must be completed prior to referral. First-tier genetic testing can be ordered by any physician. See “Information for physicians” below for more information about first-tier genetic testing.

Information for families

Why is my child being referred to a Genetics clinic?

Your child has been referred to our clinic by their doctor because they have been diagnosed with a neurodevelopmental disorder, such as global developmental delay (GDD), intellectual disability (ID), or autism.

For some children, their neurodevelopmental disorder may be caused by a genetic condition, which could be diagnosed by genetic testing.

Your child’s doctor may have done some genetic testing already, and we will explain the results to you.

The geneticist may decide that your child should have additional genetic testing and will explain this to you at the visit.

What will happen during the visit?

You will be asked questions about the pregnancy, birth and health of your child, and your child’s family history (on both biological parents’ sides, or in other words, the origin of the egg and the sperm involved at the time of your child's conception).

The geneticist (a medical doctor with expertise in genetic testing) will do a physical examination of your child, so make sure they are wearing clothes that can be easily removed.

Depending on the information you provide and the results of the physical examination, the geneticist or genetic counsellor may offer additional genetic testing for your child. If you decide to have this additional testing, another blood sample from your child may be required. Parents may also need to give a blood sample, so be sure to bring a valid health card.

How could additional genetic testing for my child be helpful?

Sometimes additional genetic testing for your child may be able to find the cause of their neurodevelopmental disorder. Different kinds of genetic conditions are detected with different types of genetic tests, so even if your child already had some genetic testing done in the past, the geneticist may recommend a new or different type of genetic test.

It can be helpful to identify the genetic condition causing your child’s neurodevelopmental disorder because:

We can know the “recurrence risk”

Some families want to understand what their chances are of having another child with the same or similar neurodevelopmental disorder as their child. Some types of genetic conditions are inherited, even if there is no family history. Other types are not inherited, so the chance of having another child with the same condition is low. It depends on the genetic cause identified in your child.

We can know treatment options

Knowing your child’s genetic diagnosis may help doctors determine which medications to use or avoid, what types of illnesses they are at increased risk for, and whether there are research studies your family can benefit from.

We can connect you with more support

Although most genetic conditions are relatively rare, many conditions have online networks where parents can share their experiences, get advice, and find out about the newest research.

Information for physicians

What is first-tier genetic testing? (This needs to be completed BEFORE referring)

All individuals with global developmental delay (GDD), intellectual disability (ID) and/or autism should be offered chromosomal microarray (CMA). CMA can be ordered by any physician, and the Microarray and Microarray Follow Up Q-PCR Testing Requisition can be found here.

Some individuals should also have Fragile X testing, particularly if there are suggestive clinical signs or a positive family history. Fragile X testing can be ordered by any physician, and the Standard Molecular Requisition (FMR1-related disorders) can be found here.

Other instructions

If first-tier genetic testing was not performed at CHEO, please attach a copy of the results along with your referral.

Who should you refer?

Individuals with a diagnosis of:

Global developmental delay (GDD) and/or intellectual disability (ID), along with results from their first-tier genetic testing (whether normal or abnormal).
Autism, if they also have abnormal results from first-tier genetic testing and/or they have syndromic features.
- If your patient has syndromic features, please list them on your referral. Syndromic features are the best predictor of a possible genetic condition.

Who should you not refer?

This clinic does not do assessments for Fetal Alcohol Spectrum Disorder (FASD). For a FASD assessment, visit our Fetal Alcohol Spectrum Disorder Assessment Clinic page.

If you have concern for a metabolic disorder:

Please direct your referral to Metabolics at CHEO.
The 2023 CCMG Position Statement has guidelines for urgent biochemical tests that you should order while your patient is awaiting assessment (Table 3).

How to make a referral to us

External referrals

Fax your referral to 613-738-4822. Please include your clinic notes/letters, and all external (ie, non-CHEO) lab results. Referrals without relevant information included will not be accepted.

CHEO internal referrals

In Epic, make a referral to Genetics. If your patient is better served by Metabolics, we will forward your referral.

More information for physicians

What are syndromic features?

Adapted from 2023 CCMG Position Statement.

Syndromic features are clinical features that, when present in individuals with neurodevelopmental disorders, may increase the likelihood of an underlying genetic condition.

Examples of syndromic features

Dysmorphic features: visible morphological findings that differ from those commonly seen in the general population or same genetic ancestry (ex. Hypertelorism, syndactyly)
Congenital malformations: a morphological anomaly of a single organ or body part that is present at birth (ex. Cleft palate, tetralogy of Fallot, polydactyly)
Abnormal head size: microcephaly, macrocephaly
Unexplained growth abnormalities: prenatal growth restriction, postnatal failure to thrive, short stature, overgrowth, etc.
Additional medical comorbidities that are not typically part of the neurodevelopmental disorder: examples include, but are not limited to, sensorineural hearing loss, vision impairment, renal disease, epilepsy, ataxia, neuromotor deficits, etc.

If your patient has a neurodevelopmental disorder as well as another clinical feature (such as one from the list above), you should be more suspicious of an underlying genetic etiology.

Comprehensive or targeted genetic testing may be offered to your patient with syndromic features and/or with a family history consistent with a genetic condition. Examples of comprehensive genetic testing include neurodevelopmental disorder multigene panels and exome sequencing. Examples of targeted genetic testing includes testing for a specific genetic condition (like Angelman syndrome, or MECP2-related Rett syndrome) or familial variant testing (if a genetic condition has already been identified in a family member).

Practical examples

2q23.1 microdeletion and microduplication syndromes: children may present with autism, intellectual disability, epilepsy, microcephaly, distinctive facies, ataxia, short stature, mild skeletal anomalies and/or eye abnormalities
4p16.3 deletion syndromes (including Wolf-Hirschhorn): children may present with autism, intellectual disability, epilepsy, growth retardation, distinctive facies, cardiac septal defects, coloboma, and/or orofacial clefts
Cowden (PTEN) syndrome: children may present initially with autism, macrocephaly, and/or benign and malignant tumours

References

Yehia L, Keel E, Eng C. The Clinical Spectrum of PTEN Mutations. Annu Rev Med. 2020 Jan 27;71:103-116. doi: 10.1146/annurev-med-052218-125823. Epub 2019 Aug 21. PMID: 31433956.

Ziats CA, Patterson WG, Friez M. Syndromic Autism Revisited: Review of the Literature and Lessons Learned. Pediatr Neurol. 2021 Jan;114:21-25. doi: 10.1016/j.pediatrneurol.2020.06.011. Epub 2020 Jun 28. PMID: 33189026.

Chromosomal microarray (CMA)

What is chromosomal microarray (CMA)?

CMA is a high-resolution genetic test to assess for chromosomal copy number variants. These include gains (duplications, triplications, etc.) and losses (deletions) of chromosomal material. Copy number variants can cause, or be strongly associated with, neurodevelopmental disorders.
CMA can also detect long contiguous stretches of homozygosity (LCSH). This is NOT a cause of neurodevelopmental disorders. LCSH may be due to the biological parents (or the egg and the sperm involved at the time of conception) of the patient having shared genetic ancestry, or, more rarely, uniparental disomy (when an individual has inherited both copies of a genomic region from the same parent or the same gamete).

Who should CMA be considered for?

Individuals diagnosed with global developmental delay (GDD), intellectual disability (ID), or autism
Individuals with multiple congenital anomalies (birth defects)
CMA is not appropriate if:
- A single gene condition is suspected (ex. Fragile X syndrome, Rett syndrome, neurofibromatosis type 1, Duchenne muscular dystrophy). Genetic testing for the specific disorder must be done in order to diagnose these conditions.
- Down syndrome (trisomy 21), or other aneuploidy is suspected (Turner syndrome, Klinefelter syndrome, trisomy 18 or 13). A karyotype is more appropriate for these indications.

How can individuals benefit from CMA?

CMA can identify the underlying genetic cause for an individual’s clinical presentation. Knowing the underlying cause can:

Provide information about recurrence risk (for family planning)
Identify associated medical risks and inform management
Facilitate access to services/support

It is important to note that CMA does not rule out all genetic conditions – only those caused by chromosomal imbalances.

Important points to review with your patient when offering CMA

CMA requires a blood sample.

It takes about 3-4 months to receive the results.

Possible results:

Normal: no copy number variants were detected
Abnormal: a copy number variant that has been previously described and is associated with a known abnormal phenotype
- A referral to a Genetics clinic is suggested.
Variant of uncertain significance: a copy number variant has been found but it is not clearly associated with the patient’s condition based on the information provided
- A referral to a Genetics clinic is suggested.
Incidental findings: rarely (<1% of the time), CMA can reveal health information unrelated to the individual’s neurodevelopmental disorder (ex. deletion of a gene which might predispose the patient to certain cancers)

How to order CMA

CMA can be ordered by any physician, and the the Microarray and Microarray Follow Up Q-PCR Testing Requisition can be found here.
Your patient’s bloodwork can be done at any community laboratory. Their sample will be shipped to CHEO and analyzed in CHEO’s Genetic Diagnostic Laboratory.

Fragile X syndrome testing

Adapted from 2023 CCMG Position Statement

What is Fragile X syndrome?

Fragile X syndrome is one of the more commonly diagnosed genetic conditions associated with intellectual disability and autism
It is an X-linked condition that can affect both individuals assigned males and or females at birth.
It is caused by a CGG triplet repeat expansion in the FMR1 gene, which is detectable ONLY by testing specifically for this expansion (and cannot be detected by chromosomal microarray or traditional gene sequencing)

Who should Fragile X testing be considered for?

Individuals diagnosed with global developmental delay (GDD), intellectual disability (ID), or autism, AND suggestive clinical signs or suggestive family history.

Suggestive clinical signs:

Macro-orchidism (may not be present until after puberty)
Relative macrocephaly
Characteristic facial features (may not be apparent in very young children): large or prominent ears, long or narrow face, tall forehead, high-arched palate and prominent jaw
Connective tissue findings: soft or velvety skin, redundant skin on dorsum of hands, hyperextensible joints, pes planus, mitral valve prolapse
Characteristic behaviours: hyperactivity, shyness, gaze avoidance, hand biting, tactile defensiveness

Suggestive family history:

Family member, even distant, with Fragile X syndrome
Family members who were assigned males or females at birthwith GDD, ID, or autism in an X-linked pattern
Female relatives (mother, maternal aunts, maternal grandmother, or other relatives with female reproductive organs) with premature menopause or ovarian insufficiency
Family members who were assigned males or females at birth with adult-onset tremor, ataxia, or parkinsonism

Other FMR1-related conditions

Fragile X syndrome is caused by a triplet repeat expansion in the FMR1 gene which is greater than 200 repeats in size. Biological mothers (or parents/people whose eggs were used for conception) of individuals with Fragile X syndrome are often premutation carriers, which means they have between 55 and 200 repeats.

Individuals with a premutation are at risk of these FMR1-related conditions:

Fragile X-associated ataxia/tremor syndrome (FXTAS): up to 20% of people may experience progressive problems with movement (such as intention tremor and ataxia) and cognition, typically starting after age 60
Fragile X-associated primary ovarian insufficiency (FXPOI): up to 20% of people with female reproductive organs may experience irregular menstrual cycles, fertility problems, and menopause about 5 years earlier than the general population

Important points to review with your patient when offering Fragile X testing

Fragile X testing is done on a blood sample. It takes about 2 months to receive the results. Please refer patients with abnormal results to Genetics.

Possible results:

Normal (repeat size <45): the patient does not have Fragile X syndrome
Intermediate or “grey zone” (repeat size 45-54): the patient does not have Fragile X syndrome, but there is a possibility of expansion of the repeat size in subsequent generations
Premutation (repeat size 50-200): the patient does not have Fragile X syndrome, but is at risk of FXTAS or FXPOI during adulthood. In addition, they have an increased chance of having children with Fragile X syndrome
Full mutation (>200 repeats): the patient is diagnosed with Fragile X syndrome

How to order Fragile X testing

Fragile X testing can be ordered by any physician, and the the Standard Molecular Requisition (FMR1-related disorders) can be found here.
Your patient’s bloodwork can be done at any community laboratory. Their sample will be shipped to CHEO and analyzed in CHEO’s Genetic Diagnostic Laboratory

Have a question related to booking or rescheduling an appointment?

Contact the Genetics Clinic at 613-737-2275. Please note that this phone is answered by a clerk who cannot provide any medical or health advice.

If you have questions about you/your child’s test results, you should direct these to the doctor who ordered the test, or to the geneticist or genetic counsellor you/your child has been in contact with.