Common Genetic Conditions

The graph above shows the incidence of common genetic conditions. Some like the Trisomies are more common with advancing maternal age whilst the others or not affected by maternal age.

Pregnancies at increased risk of common genetics conditions such as Trisomy 21 (Down Syndrome, Trisomy 18 (Edward Syndrome) , Trisomy 13 (Patau Syndrome), sex chromosome aneuploidy such as Turner Syndrome, Klinefelter Syndrome and Jacob Syndrome and microdeletions such as 22q11.2 deletion syndrome, Prader-Willi syndrome, Angelman syndrome, Cri-du-chat syndrome and those with Triploidy can be identified by the Panorama NIPT blood test. Pregnant women then have the option of prenatal diagnostic tests such as amniocentesis or CVS or newborn testing to confirm or exclude the condition. Pregnancies in which the pregnant woman or her partner are carriers of an autosomal recessive condition such as cystic fibrosis can be identified by BioArray carrier screening. If both parents are carriers of a particular condition there would be a 1 in 4 chance of having a baby with that condition and then they would have the option of prenatal diagnostic tests such as amniocentesis or CVS or newborn testing to confirm or exclude the condition.

Trisomies

Trisomy 21 (Down syndrome)

Babies with Down syndrome have copies of chromosome 21 and have intellectual disabilities that range from mild to severe. Children with Down syndrome will need extra medical care depending on the child’s specific health problems. Early intervention has allowed many individuals with Down syndrome to lead healthy and productive lives. The presence of medical conditions, like heart defects, can affect the lifespan in these children and adults; however, most individuals with Down syndrome will live into their 60s. Miscarriage occurs in about 30% of pregnancies with Down syndrome while overall about 1 in 700 babies are born with Down syndrome.

Trisomy 18 (Edwards syndrome)

Babies with trisomy 18 have three copies of chromosome 18 and have severe intellectual disabilities and birth defects typically involving the heart, brain, and kidneys. Babies with trisomy 18 can also have visible birth defects such as an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), a small head, clubbed feet, underdeveloped fingers, and toes, and a small jaw. Unfortunately, most pregnancies with trisomy 18 will miscarry. If born alive, most affected babies with trisomy 18 will pass away within the first few weeks of life. About 10 percent survive to their first birthday. Trisomy 18 occurs in approximately 1 in 3,000 live births.

Trisomy 13 (Patau syndrome)

Babies with trisomy 13 have three copies of chromosome 13 and have severe intellectual disabilities. They often have birth defects involving the heart, brain, and kidneys. Visible abnormalities include extra fingers and/or toes or an opening in the lip, with or without an opening in the palate. Given the severe disabilities, most pregnancies affected by trisomy 13 will miscarry. If born alive, most affected babies with trisomy 13 will pass away within the first few weeks of life. About 10 percent survive to their first birthday. Trisomy 13 occurs in approximately 1 in 5,000 live births.

Triploidy

Babies with triploidy have a complete extra set of chromosomes for a total of 69 chromosomes instead of the usual 46. At 10 weeks gestation, one in 1,000 pregnancies is affected by triploidy. It is extremely rare for these pregnancies to reach term as they typically spontaneously miscarry early in pregnancy. Those few liveborns usually pass away within days of delivery due to heart, brain, and kidney problems. Babies with triploidy also often have birth defects affecting the extremities and face.

Carrying a baby with triploidy can increase a mother’s risk for a variety of conditions: pre-eclampsia (which can lead to seizures) and excessive bleeding after delivery. In rare instances, triploid pregnancies can persist and progress to a type of cancer called choriocarcinoma. Knowing about triploidy allows the physician to monitor the health of the mother appropriately

Sex Chromosome Aneuploidy

Monosomy X (Turner syndrome)

Babies with monosomy X are females who have one X chromosome instead of two. Unfortunately, a high proportion of pregnancies with monosomy X will result in a miscarriage in the first or second trimester of pregnancy. Babies with monosomy X that make it to term may have heart defects, learning difficulties, and infertility. In most cases, girls with monosomy X will need extra medical care including hormone therapy at various stages of life.

XXY Syndrome (Klinefelter Syndrome)

Babies with XXY syndrome have two X chromosomes and one Y chromosome (XXY). This condition can be associated with learning difficulties and behavioral problems. People with Klinefelter syndrome might be infertile. About 1 in 1,000 babies will be born with Klinefelter syndrome.

Triple X syndrome

Babies with Triple X syndrome have three X chromosomes (XXX). Children with this condition could be taller than average and might experience learning difficulties or behavioural problems. Approximately 1 in 1,600 babies will be born with three X chromosomes.

XYY Syndrome (Jacob’s Syndrome)

Babies with XYY syndrome have one X chromosome and two Y chromosomes (XYY). Most babies with XYY syndrome do not have any birth defects. Children with XYY could be taller than average and have an increased chance for learning, speech, and behavioural problems. Approximately 1 in 1,300 babies will be born with one X chromosome and two Y chromosomes.

Microdeletions

22q11.2 deletion syndrome

22q11.2 deletion syndrome, also called DiGeorge syndrome or Velo-Cardio-Facial syndrome (VCFS), is caused by a missing piece of chromosome number 22. About one in every 2,000 babies is born with 22q11.2 deletion syndrome. The majority of children with this disorder have heart defects, immune system problems, and specific facial features. Most children with 22q.11.2 deletion syndrome have mild-to-moderate intellectual disability and speech delays; some will also have low calcium levels, kidney problems, feeding problems, and/or seizures. About one in five children with 22q11.2 deletion syndrome have autism spectrum disorder; 1 in 4 adults with 22q11.2 deletion syndrome have a psychiatric illness, like schizophrenia.

Prader-Willi syndrome**

Prader-Willi syndrome occurs when either a small piece of chromosome 15 is missing or when both copies of chromosome 15 come from the same parent (called uniparental disomy, or UPD). Babies with Prader-Willi syndrome have low muscle tone and problems with growth and feeding. Children with Prader-Willi syndrome have delayed milestones, short stature, rapid weight gain leading to obesity, and intellectual disability. About 1 in 10,000 babies are born with Prader-Willi syndrome.

Angelman syndrome**

Angelman syndrome happens when either a small piece of chromosome 15 is missing, or when both copies of chromosome 15 come from the same parent (called uniparental disomy, or UPD). About 1 in 12,000 babies are born with Angelman syndrome. Babies and children with Angelman syndrome have severe intellectual disability, delayed milestones, seizures, and problems with balance and walking.

1p36 deletion syndrome

1p36 deletion syndrome, also referred to as Monosomy 1p36 syndrome is caused by a missing piece of chromosome 1. Children with 1p36 deletion syndrome have intellectual disabilities. Most have heart defects and weak muscle tone. About half of affected individuals have seizures (epilepsy), behavioural problems, and hearing loss. Some children with 1p36 deletion syndrome also have vision problems or additional birth defects of other organs. About 1 in 5,000 newborn babies has 1p36 deletion syndrome.

Cri-du-chat syndrome

A missing piece of chromosome 5 causes Cri-du-chat syndrome, also called 5p- (5p minus) syndrome. The name “Cri-du-chat” was given to this syndrome due to the high-pitched, cat-like cry that babies with this syndrome often make. Babies with Cri-du-chat syndrome typically have low birth weight, a small head size, and weak muscle tone. Feeding and breathing problems are common in infancy. Children with this disorder have moderate-to-severe intellectual disability, including speech and language delays. They may also have growth delays, behavior problems, and some have curvature of the spine (scoliosis). About one in every 20,000 babies is born with Cri-du-chat syndrome. They may also have heart defects, growth delay, behaviour problems and some have curvature of the spine.

Autosomal Recessive Conditions

Cystic Fibrosis

Cystic Fibrosis is an autosomal recessive disorder that affects many different areas of the body including the lungs, digestive system, and fertility. Cystic Fibrosis does not affect intelligence. Signs and symptoms of Cystic Fibrosis start in early childhood and include delayed growth caused by problems in digestion and repeated lung infections that lead to permanent lung damage. Children and adults with Cystic Fibrosis usually have frequent hospitalizations because of lung infections. Over time, complications of Cystic Fibrosis can lead to lung transplants and early death. There are treatments for Cystic Fibrosis that can lessen the severity of the symptoms; however, there is currently no cure.

Cystic Fibrosis is caused by a change, or mutation, in both copies of the CFTR gene pair. These mutations cause the genes to not work properly or not work at all. When both copies of this gene do not work correctly, mucus and other body fluids become thick and sticky. This causes problems with how the lungs, digestive system, and other body systems function and leads to the symptoms described above. Although most CFTR gene mutations cause classic CF, there are some specific CFTR mutations that cause less severe symptoms, and some only affect male fertility. A small number of CF carriers may have mild respiratory or other symptoms.

Duchenne/Becker Muscular Dystrophy

Duchenne and Becker Muscular Dystrophy are inherited disorders called “Dystrophinopathies” that cause progressive breakdown and weakness of both skeletal and heart muscle. In Duchenne Muscular Dystrophy, the muscle weakness usually begins around 3 to 5 years of age and worsens over time. By the teenage years, the muscle degeneration and weakness also starts to involve the muscles of the lungs and heart. In Becker Muscular Dystrophy, the signs and symptoms are milder and begin later in childhood. For both conditions, it is more common for boys to be affected than girls. Children and adults with Duchenne/Becker Muscular Dystrophy need physical and occupational therapy and lifelong medical treatment. Most boys with Duchenne Muscular Dystrophy will need a wheelchair by their mid to late teenage years; boys with Becker Muscular Dystrophy are often in their late teens or early adulthood before they need a wheelchair. A variable degree of intellectual disability may occur and is more common in children with Duchenne than in children with Becker. Presently there is no cure for Duchenne/Becker Muscular Dystrophy. With current medical treatments, survival is common into the 20s and 30s with Duchenne Muscular Dystrophy and into the 40s with Becker Muscular Dystrophy. Some males have a separate form of Dystrophinopathy called DMD-Associated Dilated Cardiomyopathy, which does not include skeletal muscle weakness. DMD-Associated Dilated Cardiomyopathy causes progressive heart problems where one or more chambers of the heart dilate, the heart muscle weakens, and congestive heart failure occurs. Symptoms typically start between the ages of 20 and 40 years and lifespan is shortened. About 1 in every 3500 males is born with Duchenne Muscular Dystrophy and about 1 in every 18,500 boys is born with Becker Muscular Dystrophy. DMD-Associated Dilated Cardiomyopathy is rare.

Some female carriers develop heart problems such as dilated cardiomyopathy and some have other symptoms of Duchenne/Becker Muscular Dystrophy such as mild to moderate muscle weakness. In rare cases, female carriers may have more serious symptoms.

Duchenne/Becker Muscular Dystrophy is caused by a change, or mutation, in the DMDgene. This mutation causes the gene to not work properly or not work at all. When this gene does not work correctly, it leads to a lack of dystrophin, a protein normally found in muscle cells. Muscle cells in the skeleton and heart that don’t have enough dystrophin gradually stop working, leading to the symptoms described above. It is sometimes but not always possible to tell just by the mutation whether a boy will have the Duchenne or Becker form of this condition.

Fragile X Syndrome

Fragile X Syndrome is an X-linked inherited disorder. It is the most common inherited cause of intellectual disability and occurs in about 1 in 4000 males and 1 in 8000 females. Boys with Fragile X Syndrome typically have more serious learning and behavior problems than girls. On average, boys have moderate to severe intellectual disability. Behavior and emotional problems are common, and autism spectrum disorder is sometimes present. Symptoms in girls can range from none to severe intellectual disability; however, they are most likely to be mild. At this time there is no cure for Fragile X Syndrome and treatment is based on symptoms.

Fragile X Syndrome is caused by a mutation (change) in the FMR1 gene known as a CGG repeat. Humans typically have between 6 and 44 copies of CGG in the FMR1 gene. In people with Fragile X Syndrome, there are more than 200 copies of CGG. The large number of repeated CGGs causes the gene to turn off and not work properly. This leads to the specific set of learning and development problems found in Fragile X Syndrome.

A carrier for Fragile X Syndrome is someone who has a mutation (change) in one FMR1 gene. This change is called a ‘premutation’ and has between 55 and 200 CGG copies. Women who are premutation carriers have an increased chance of having children affected with Fragile X Syndrome. Occasionally, females with a premutation may have issues related to attention span such as Attention Deficit Disorder and some may have behavior problems, social anxiety, and/or difficulty with social skills. Males with a premutation tend to have a higher rate of these types of problems.

Spinal Muscular Atrophy

Spinal Muscular Atrophy, also called SMA, is a serious autosomal recessive disorder that typically begins in infancy or childhood and causes worsening muscle weakness, decreased ability to breathe, and loss of motor skills. Most children with Spinal Muscular Atrophy have one of the early-onset forms with symptoms that begin in infancy, with death often occurring before the age of two. Some children have juvenile-onset SMA and develop muscle weakness and other symptoms later in childhood. In rare cases, symptoms do not begin until early adulthood, are less severe, and do not affect lifespan. Currently there is no cure for Spinal Muscular Atrophy, although treatments are available that may lessen some of the symptoms in some patients.

Spinal Muscular Atrophy is caused by a change, or mutation, in both copies of the SMN1 gene pair. These mutations, which often delete part or all of these genes, cause the genes to work improperly or not work at all. When both copies of the SMN1 gene are missing or do not work correctly, it leads to the symptoms described above