In many countries, it is standard practice to test every newborn for numerous genetic disorders. Using blood samples from a heel prick taken in the first 48 hours of life, doctors look for genetic variants associated with conditions that might otherwise be missed. These are typically conditions that respond well to early treatment to prevent potentially serious complications, permanent disability, and even death.
However, results must be carefully interpreted and contextualized. A problem on chromosome 7 might result in serious lung problems due to cystic fibrosis, or manifest as mild respiratory issues. But few diseases are the result of a single genetic mutation. Instead, multiple genes interact with each other and with environmental factors to influence our risk of illness and the severity of any given disease or condition.
Thankfully, newborn genetic testing is usually provided in an environment where the results can be properly explained to help alleviate potential concerns. Parents are typically provided with appropriate resources and guided through next steps to access treatments where appropriate. For more on the ethics of genetic testing for kids, see my first post in this series. For now, though, let’s look at which tests are available as standard and why you might want to get additional tests for your kids.
Newborn heel prick testing
The United States, Canada, New Zealand, and many other countries have long had programs designed to test newborns for the most severe and common genetic disorders. These programs have saved thousands of lives and are regularly updated based on our current knowledge of gene-disease interactions.
New Zealand currently screens newborns for 24 metabolic disorders, including the following genetic disorders:
- Amino acid disorders (for example, phenylketonuria and maple syrup urine disease [PKU and MSUD])
- Fatty acid oxidation disorders (for example medium-chain acyl-CoA dehydrogenase deficiency [MCAD])
- Congenital hypothyroidism (CH)
- Cystic fibrosis (CF)
- Congenital adrenal hyperplasia (CAH)
- Biotinidase deficiency
- Severe combined immune deficiency (SCID).
Newborn screening in the US
Newborns are screened for at least 29 health conditions in the United States (at the time of writing). Altogether, screening is available for 35 core conditions and 26 secondary conditions. The core conditions make up the Recommended Uniform Screening Panel (RUSP). Most states allow parents to opt out of newborn testing for religious or other reasons. Check this list to see which disorders are included on standard newborn screening in your state.
Although testing varies by state, the RUSP core conditions are as follows:
- Metabolic Disorders:
- Organic acid conditions:
- Propionic acidemia
- Methylmalonic acidemia (methylmalonyl-CoA mutase)
- Methylmalonic acidemia (cobalamin disorders)
- Isovaleric acidemia
- 3-Methylcrotonyl-CoA carboxylase deficiency
- 3-Hydroxy-3-methyglutaric aciduria
- Holocarboxylase synthase deficiency
- ß-Ketothiolase deficiency
- Glutaric acidemia type I
- Fatty acid oxidation disorders:
- Carnitine uptake defect/carnitine transport defect
- Medium-chain acyl-CoA dehydrogenase deficiency
- Very long-chain acyl-CoA dehydrogenase deficiency
- Long-chain L-3 hydroxyacyl-CoA dehydrogenase deficiency
- Trifunctional protein deficiency
- Amino acid disorders:
- Argininosuccinic aciduria
- Citrullinemia, type I
- Maple syrup urine disease
- Classic phenylketonuria
- Tyrosinemia, type I.
- Organic acid conditions:
- Primary congenital hypothyroidism
- Congenital adrenal hyperplasia.
- S,S disease (Sickle cell anemia)
- S, βeta-thalassemia
- S,C disease.
- Biotinidase deficiency
- Critical congenital heart disease
- Cystic fibrosis
- Classic galactosemia
- Glycogen Storage Disease
- Type II (Pompe)
- Hearing loss
- Severe combined Immunodeficiencies
- Mucopolysaccharidosis Type 1
- X-linked Adrenoleukodystrophy
- Spinal Muscular Atrophy due to homozygous deletion of exon 7 in SMN1.
A list of the current 26 secondary conditions can be seen here.
Additional genetic testing for kids
Parents may wish to consider genetic testing over and above those issues assessed through the heel prick test. Additional tests could help inform the choice of food and supplements for infants and young children. For instance, adults often like to get tested for lactose intolerance, but did you know that there’s a genetic test for congenital lactose intolerance?
There are also genetic tests that reveal problems with red blood cell formation and how we process iron, as well as tests for gluten intolerance and blood clotting problems. These types of tests could help parents identify the likely cause of digestive issues, so as to avoid further symptoms and promote healthy digestion. Testing could also help parents make informed decisions over the use of multivitamins and iron supplements, omega-3 fatty acids, and certain herbs.
If you do decide to have your child tested for the following conditions, be sure to talk to a qualified health care provider when interpreting the results. Significantly restricting a child’s diet or deciding to use or avoid supplements could have unintended health consequences.
|Alpha-1 Antitrypsin Deficiency||SERPINA1|
|Celiac Disease||HLA-DQB1 and HLA-DQA1|
|Hereditary Hemochromatosis (HFE‑Related)||HFE|
|Hereditary Thrombophilia||F2 and F5|
|Congenital alactasia (lactose intolerance in infancy)||LCT|
APOE4 and Concussion
Some gene variants have been linked to an increased risk of severe consequences of traumatic brain injury (TBI). The genes identified as affecting outcomes following TBI include those that influence inflammation in the aftermath of injury, those that are involved in repair and neuroplasticity, and catecholamine genes that modulate cognitive capacity before and after injury.
Apolipoprotein E (apoE, protein; APOE, gene) is the most studied and well-known gene associated with concussion, TBI, CTE, and neurotrauma. This gene is involved in cholesterol metabolism and apoE is the major apolipoprotein produced in the central nervous system (CNS) by astrocytes and microglia, as well as in neurons experiencing stress. ApoE is thought to promote repair and growth in neurons, help maintain synaptodendritic connections, and mediate inflammation in the brain.
Around 14% of people worldwide are thought to have the APOE4 variant, with most (79%) carrying the APOE3 variant and the rest (7%) carrying APOE2 (R). As noted above, SNPs that potentially influence the expression of the APOE gene may also modulate risk of brain injury and disease. These SNPs include –219 G/T (rs405509), –427 rs769446 T/C, and –491 A/T (rs449647).
The APOE4 variant has been associated in some studies with a higher propensity for chronic traumatic encephalopathy (CTE). This is a neurodegenerative condition seen in individuals who have incurred multiple head traumas, often from boxing, hockey, football, or other sporting activity. APOE4 has also been associated with familial and sporadic Alzheimer’s disease as well as multiple sclerosis and recovery after a variety of health issues.
Research found that older pro-football players with the APOE4 variant had lower scores on cognitive tests than those with different APOE alleles. The data on APOE4 is not conclusive, however. Indeed, some research suggests that the combination of APOE4 and the APOE promoter -219 T allele is associated with a history of concussion, while other research failed to find any such association (R, R). In fact, one study found a significantly lower risk of concussion associated with the APOE4 allele.
In one key study, individuals with APOE4 and a history of TBI had a 10-fold increase in the risk of developing Alzheimer’s disease, while those with APOE4 and no history of TBI had a twofold increased risk; in people with a history of TBI but who did not have the APOE4 variant there was no increased risk of AD.107
Other genes that appear to play a role in the outcome of TBI include those that influence inflammation via tumor necrosis factor-alpha (TNF-alpha) and levels of interleukin-1 and interleukin-6 (IL-1 and IL-6). Several studies have investigated the association between the IL-6 promoter polymorphisms –174 C/G, –572 G/C, and –597 G/A and outcome following severe TBI. Some studies suggest that survival rates are higher in people carrying the GG genotype for -174, although results are inconsistent (R).
There is currently no conclusive evidence to suggest that a single gene variant determines whether a child will develop Alzheimer’s disease later in life or be less likely to survive a severe TBI. As such, there is considerable debate over the merits of keeping kids out of contact sports based solely on their APOE status. Instead, it would appear sensible simply to take precautions for all children, including using proper protective gear, minimizing aggressive play, supporting good blood sugar regulation and inflammatory processes, and giving adequate time for healing and recovery if injuries do occur.
MTHFR and kids
I’ve written before about the MTHFR gene that influences the conversion of folic acid and food folate into active L-methylfolate in the body. Parents may be interested in finding out if their child has a variant of this gene that impairs this metabolic process as this could influence their choice of food supplements and diet. High levels of unmetabolized folic acid may also present some risks to health, although research is ongoing in this area.
Fun genetic tests for kids
Genetic tests might seem all doom and gloom, but tests can also provide an opportunity to learn about genes in a fun and interactive way. Some genetic tests, for instance, look for traits, rather than disease risks, meaning that there’s little concern over psychological impact. That said, genetic tests risk revealing family secrets or marking out a kid as different from their siblings. No one wants to be the ‘melanoma kid’, but kids might also feel judged if tests reveal they have dry earwax. As parents, you probably know your child best, so consider these factors before testing.
Kids might want to know if they have a genetic variant that means they can smell asparagus metabolites in urine, for example (rs4481887, near OR2M7). Kids can also find out if they are genetically predisposed to dislike the taste of cilantro, while other fun genetics tests include looking at genes linked to:
|Musical ability||AVPR1A and SLC6A4|
|Type of earwax (dry or wet)||ABCC11|
|Whether hair lightens in the sunshine||MC1R|
|Predisposition to a fear of heights||Olfr151|
|Misophonia (especially hatred of the sound of chewing)||TENM2|
|Whether they’ll be especially delicious to mosquitoes, or reactive to bites|
|Photic sneeze reflex (i.e. whether or not you sneeze in bright sunlight)||rs10427255, near ZEB2, and rs11856995, near NR2F2.|
Many genes are also thought to affect the likelihood of a chin cleft or dimples, as well as in determining detached or attached ear lobe type.
To test or not to test
In conclusion, genetic testing for kids is practiced as standard in most developed countries, whether we realize it or not. Such tests can save lives and dramatically improve quality of life, but only if they are accompanied by proper medical care. Tests for adult-onset conditions or diseases that have no modifiable risk factors are much more controversial, however. These need to be carefully considered and, in most cases, are probably better delayed until the child can be involved in the decision-making process.
While what happens to us in childhood undoubtedly has an effect on our risk of developing type 2 diabetes, cardiovascular disease, and even Alzheimer’s, the interaction between genes, childhood behavior, and adult-onset diseases are still emerging.
So, until research demonstrates that specific childhood behaviors can significantly reduce the risk of health problems later in life, the sensible approach seems to be to promote exactly the kinds of healthy behaviors we already encourage in children: eat your greens, minimize sun exposure, stay physically active, and avoid head injuries by wearing bike helmets and proper protective gear.