Screening for chromosomal abnormalities with Noninvasive Prenatal Select

Sema4 Noninvasive Prenatal Select is a highly accurate test that can detect chromosomal abnormalities as early as 9 weeks into pregnancy. It screens for common chromosome aneuploidies, sex chromosome aneuploidies, and microdeletions. If you would like to know, Noninvasive Prenatal Select can also reveal the sex of your baby.

Autosomal Aneuploidies

Trisomy 21 (Down syndrome)

One in 800 newborns is affected by trisomy 21 (also known as Down syndrome). The risk of a newborn being affected by trisomy 21 increases with maternal age. Symptoms of this condition typically include intellectual disability, characteristic facial features, and weak muscle tone. Delayed development and behavioral problems are often reported in children with Down syndrome. Additionally, about half of children with trisomy 21 are born with a heart defect and some have gastrointestinal abnormalities. People with trisomy 21 have an increased risk of developing medical conditions such as gastroesophageal reflux, celiac disease, hypothyroidism, hearing and vision problems, leukemia, and Alzheimer’s disease. The life expectancy of individuals with Down syndrome can be over sixty years, however, this can vary greatly depending on the severity of the associated abnormalities.

Trisomy 18 (Edwards syndrome)

One in 5,000 infants is born with trisomy 18 (also known as Edwards syndrome). The risk of a newborn being affected by trisomy 18 increases with maternal age. Symptoms of trisomy 18 include heart defects, a small head that is abnormally shaped, a small mouth and jaw, clenched fists with overlapping fingers, and other organ abnormalities. Due to the presence of several life-threatening medical problems, many individuals with trisomy 18 die before birth or within their first month. Five to 10 percent of children with this condition live past their first year, and these children often have severe intellectual disability.

Trisomy 13 (Patau syndrome)

One in 16,000 newborns is affected by trisomy 13 (also known as Patau syndrome). The risk of a newborn being affected by trisomy 13 increases with maternal age. Infants born with trisomy 13 have severe intellectual disability and physical malformations, including heart defects, brain or spinal cord abnormalities, small or poorly developed eyes, extra fingers or toes, cleft lip and/or cleft palate, and weak muscle tone. Due to the presence of several life-threatening medical problems, many infants with trisomy 13 die within their first days or weeks of life. Only five to 10 percent of children with this condition live past their first year.

Trisomy 16

Trisomy 16 is an extremely rare chromosomal condition in live births. The risk of trisomy 16 increases with maternal age. Complete trisomy 16 is generally considered to be incompatible with life and commonly results in miscarriage at 8 to 15 weeks’ gestation, with a few cases surviving into the second trimester or near-term. Infants with mosaic trisomy* 16 may survive to term with serious disability, including growth failure, congenital heart defects, and other abnormalities.

Trisomy 22

Trisomy 22 is an extremely rare chromosomal condition in live births. The risk of trisomy 22 increases with maternal age. It is the second most common cause of miscarriage during the first trimester of pregnancy. Because of multiple malformations, just 1 in 30,000 to 50,000 cases survive to birth. In the rare case that an infant with true trisomy 22 survives to birth, life expectancy is short. Patients with mosaic trisomy* 22 usually have cardiac anomalies, growth delays, and intellectual disability.

Trisomy 15

Trisomy 15 is an extremely rare chromosomal condition in live births. The risk of trisomy 15 increases with maternal age. Complete trisomy 15 is not compatible with life. Symptoms of mosaic trisomy 15 may include growth delay before or after birth, intellectual disability, and distinct facial features. Mosiac trisomy* 15 can also cause other physical abnormalities, such as genital abnormalities, malformation of the fingers and toes, and malformation of the skeleton, spine, and neck. Trisomy 15 is associated with an increased risk for uniparental disomy (UPD) for chromosome 15. UPD is when a child inherits two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. Children with UPD for chromosome 15 may be affected by Prader-Willi syndrome or Angelman syndrome.

*Mosaicism is when only some of the cells in the body contain the chromosomal abnormality.

Sex Chromosome Aneuploidies

Monosomy X (Turner syndrome)

One in 2,500 girls is born with monosomy X (also known as Turner syndrome). Physical features of monosomy X may include short stature, extra folds of skin on the neck, low hairline at the back of the neck, swelling of the hands and feet, and skeletal and kidney problems. It can also cause premature ovarian failure or early loss of ovarian function, resulting in a failure to begin puberty and infertility. Approximately one-third of girls affected by monosomy X have heart problems, such as defects in the aorta or aortic valve. This condition can also cause developmental delays, learning disabilities, and behavior problems. This condition is associated with a three-fold increase in mortality and overall life expectancy is reduced by up to 13 years.

XXX (Trisomy X syndrome)

One in 1,000 girls is affected by Trisomy X syndrome. People with this condition may be taller than their peers, but usually have normal physical characteristics and sexual development. Girls with Trisomy X have an increased risk of learning disabilities, delayed speech, and delayed language development. Additionally, 10% of girls affected by this condition develop seizures or kidney problems. Most girls with this condition are expected to have a normal life span, however, rare cardiac abnormalities and associated risks have been reported.

XXY (Klinefelter syndrome)

One in 1,000 newborn boys is affected by Klinefelter syndrome. The risk of Klinefelter syndrome increases with maternal age. Boys affected by this condition typically have small testes that produce low levels of testosterone. This causes many symptoms of Klinefelter syndrome, including delayed or incomplete puberty, tall stature, gynecomastia (breast enlargement), reduced facial and body hair, and infertility. Some affected individuals also have genital differences, including undescended testes (cryptorchidism), the opening of the urethra is on the underside of the penis (hypospadias), or an unusually small penis (micropenis). Males with Klinefelter syndrome also have an increased risk of breast cancer and a chronic inflammatory disease called systemic lupus erythematosus. Most individuals with this condition are expected to have a normal lifespan.

XYY syndrome

One in 1,000 newborn boys is affected by XYY syndrome. Most people with XYY syndrome have normal sexual development and are fertile. Although males with this condition may be taller than average, this chromosomal change typically causes no unusual physical features. There is an increased risk of learning disabilities and delayed development of speech and motor skills. Other less common symptoms include weak muscle tone, hand tremors or other involuntary movements, and behavioral difficulties. There is also a slightly increased chance of autism spectrum disorder. Individuals with this condition are expected to have a normal lifespan.

Microdeletions

22q11.2 deletion

One in 4,000 newborns is affected by 22q11.2 deletion syndrome. However, this condition may be underdiagnosed due to variable symptoms that can affect almost any part of the body. Symptoms may include heart abnormalities, cleft palate, distinct facial features, frequent infections, autoimmune disorders, breathing problems, kidney abnormalities, low levels of calcium, decreased platelet counts, feeding difficulties, digestive problems, hearing loss, and skeletal abnormalities. Many children with 22q11.2 deletion have learning disabilities and developmental delays. Affected children are more likely to have attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder. Adults with this condition are at an increased risk of developing psychiatric illnesses, including schizophrenia, depression, anxiety, and bipolar disorder. 22q11.2 deletion syndrome is associated with an increased mortality rate and life expectancy can vary depending on the severity of the abnormalities.

1p36 deletion

One in 5,000 people is affected by 1p36 deletion. People with this condition have severe intellectual disability. Most affected individuals do not speak or speak very few words. They may have temper tantrums, bite themselves, or exhibit other behavior problems. 1p36 deletion can cause structural brain abnormalities, seizures, weak muscle tone, and problems swallowing. It also causes distinctive facial features, including deep-set eyes, sunken appearance of the middle of the face, long area between the nose and mouth, pointed chin, and abnormally shaped, low-set ears. Hearing and vision problems are common, and some people with 1p36 deletion have skeletal, heart, digestive, kidney, or genitalia problems. The life expectancy of individuals with 1p36 deletion syndrome is not currently known.

4p16 deletion (Wolf-Hirschhorn syndrome)

One in 20,000 people is affected by 4p16 deletion (also known as Wolf-Hirschhorn syndrome). This condition causes distinctive facial features, including a broad, flat nasal bridge and a high forehead, resulting in a “Greek warrior helmet” appearance. The eyes are widely spaced and may be protruding. Other characteristic facial features include a shortened distance between the nose and upper lip (a short philtrum), a downturned mouth, a small chin (micrognathia), and poorly formed ears with small holes (pits) or flaps of skin (tags). People with 4p16 deletion may have delayed growth and development, weak muscle tone, short stature, intellectual disability, and seizures. Additional features of Wolf-Hirschhorn syndrome include skin changes such as mottled or dry skin, skeletal abnormalities such as abnormal curvature of the spine (scoliosis and kyphosis), dental problems (including missing teeth), and an opening in the roof of the mouth (cleft palate) and/or in the lip (cleft lip). Wolf-Hirschhorn syndrome can also cause abnormalities of the eyes, heart, genitourinary tract, and brain. The life expectancy of individuals with Wolf-Hirschhorn syndrome can vary, however, there is an increased mortality rate for children diagnosed with this syndrome.

5p15 deletion (Cri-du-chat syndrome)

One in 20,000 newborns is affected by 5p15 deletion (also known as cri-du-chat syndrome). Infants with this condition make a high-pitched cry that sounds similar to a cat. Other symptoms include intellectual disability, delayed development, low muscle tone, low birth weight, and small head size (microcephaly). 5p15 deletion also causes distinctive facial features of this condition include widely-set eyes (hypertelorism), low-set ears, a small jaw, and a rounded face. Some children with cri-du-chat syndrome are born with a heart defect. Most individuals with cri-du-chat syndrome have a normal lifespan, however, individuals with severe defects can have life-threatening complications.

15q11.2-q13 deletion (Prader-Willi syndrome or Angelman syndrome)

15q11.2-q13 deletion is associated with two different chromosomal conditions – Prader-Willi syndrome and Angelman syndrome. One in 23,000 newborns is affected by Prader-Willi syndrome. Prader-Willi syndrome is a complex genetic condition that affects many parts of the body. Symptoms of this condition include weak muscle tone, poor growth, intellectual disability, developmental delays in infancy, and chronic overeating and obesity in childhood. People with Prader-Willi syndrome often have behavioral and sleeping problems. Both affected males and affected females have underdeveloped genitals. Puberty is delayed or incomplete, and most affected individuals are infertile. There is an increased mortality rate in children with Prader-Willi syndrome, particularly due to complications associated with obesity, cardiac, and respiratory issues.

One in 21,000 newborns is affected by Angelman syndrome. Angelman syndrome may result in developmental delays, intellectual disability, severe speech impairment, and problems with movement and balance. People with this condition tend to have a happy, excitable demeanor with a short attention span, hyperactivity, and sleeping difficulties. While many symptoms of this condition tend to improve with age, intellectual disability, severe speech impairment, and seizures persist. Most individuals with Angelman Syndrome have a normal lifespan, however, lifespan may be 10 to 15 years shorter in the more severe cases.

11q23 deletion (Jacobsen syndrome)

One in 100,000 newborns is affected by 11q23 deletion (also known as Jacobsen syndrome). The signs and symptoms of Jacobsen syndrome vary considerably. Symptoms of the condition include delayed development, learning disabilities, behavioral difficulties, and short attention spans. In some cases, this may result in a diagnosis of attention-deficit/hyperactivity disorder (ADHD). 11q23 deletion causes distinctive facial features, including small and low-set ears, widely-set eyes (hypertelorism), droopy eyelids, skin folds covering the inner corner of the eyes (epicanthal folds), a broad nasal bridge, downturned corners of the mouth, a thin upper lip, a small lower jaw, and a large head (macrocephaly). More than 90% of people with 11q23 deletion also have a bleeding disorder called Paris-Trousseau syndrome. The life expectancy of people with this condition is unknown, although affected individuals have lived into adulthood.

8q24 deletion (Langer-Giedion syndrome)

8q24 deletion (also known as Langer-Giedion syndrome) is an extremely rare chromosomal condition. People with this condition have multiple noncancerous (benign) bone tumors called osteochondromas. Multiple osteochondromas may result in pain, limited range of joint movement, and pressure on nerves, blood vessels, the spinal cord, and tissues surrounding the osteochondromas. 8q24 deletion also results in a distinctive appearance, including sparse scalp hair, a rounded nose, a long flat area between the nose and the upper lip (philtrum), and a thin upper lip. Other symptoms may include short stature and intellectual disability. Most individuals with 8q24 deletion are expected to have a normal lifespan.