Disorders detected by Invitae NIPS DISORDER CHROMOSOME DESCRIPTION PREVALENCE COMMON TRISOMIES Down Trisomy 21 Although some pregnancies with trisomy 21 end in pregnancy loss, trisomy 21 Trisomy 21 is the syndrome often can lead to live birth. Individuals with trisomy 21 have variable physical most common features and intellectual disability. Some of the common features of trisomy 21 chromosome abnor- include heart defects, low muscle tone, and differences in facial features. In ad- mality, occurring in 1 dition, cognitive impairment can range from mild to severe. People with Down in 700 to 1 in 800 live syndrome have a higher risk for certain medical conditions, such as hearing births. problems, thyroid problems, childhood leukemia, and Alzheimer’s disease. People with Down syndrome may require supervision throughout their lives. However, many people with Down syndrome are increasingly attending school and holding jobs. Many individuals with Down syndrome live into adulthood. Edwards Trisomy 18 Although many pregnancies with trisomy 18 result in miscarriage or stillbirth, Trisomy 18 occurs syndrome trisomy 18 can result in live birth. Individuals with trisomy 18 have severe in 1 in 6000 to 1 in intellectual disability and abnormalities involving multiple organs. Some of 8000 live births. the common features of trisomy 18 include heart defects, brain abnormalities, musculoskeletal problems, cleft lip and palate, and low birth weight. Although less than 10% of babies with trisomy 18 will live past 1 year of age, some peo- ple with this condition can live years or even decades. Patau Trisomy 13 Although the majority of pregnancies with trisomy 13 result in miscarriage or Trisomy 13 occurs in syndrome stillbirth, trisomy 13 can result in live birth. Individuals with trisomy 13 have approximately 1 in severe intellectual disability and abnormalities involving multiple organs. 12,000 live births. Some of the common features of trisomy 13 include heart defects, omphalo- cele, brain abnormalities such as holoprosencephaly, cleft lip and palate, and other features. Although less than 10% of babies with trisomy 13 will live past 1 year of age, some people with this condition can live years or even decades. SEX CHROMOSOME DISORDERS Turner Monosomy X Monosomy X is a condition that is caused by having one X sex chromosome Approximately 1 in syndrome and an absent second sex chromosome (one sex chromosome instead of 2500 females are two sex chromosomes). Many pregnancies with monosomy X will result in a born with mono- pregnancy loss; however, monosomy X is compatible with continued survival somy X. and live birth. Females with monosomy X have variable phenotypes. Typically, females with monosomy X have normal intelligence; however, learning dis- abilities are possible and variable. Some of the common features of mono- somy X include heart defects, kidney abnormalities, short stature, congenital lymphedema, and primary amenorrhea. XXX 47,XXX XXX syndrome is a condition that is caused by a female having an extra copy Approximately 1 in syndrome of the X sex chromosome (three copies of the X chromosome instead of the 1000 females are usual two copies). XXX syndrome is likely to result in live birth. XXX syndrome born with XXX syn- is usually not associated with intellectual disability or severe birth defects. drome. Some of the common features of XXX syndrome include delayed speech and motor development. Females with XXX syndrome can be taller than average height. Pubertal development and fertility is usually normal. Klinefelter 47,XXY XXY syndrome is a condition that is caused by a male having an extra copy of Approximately 1 in syndrome the X sex chromosome (two copies of the X chromosome and one copy of the 600 males are born Y chromosome rather than the usual one copy of each). XXY syndrome is likely with XXY syndrome. to result in live birth. Males with XXY syndrome have variable phenotypes. Some of the common features of XXY syndrome include learning disabilities, delayed speech and language development, taller stature, hypogonadism, and risk of infertility. Jacobs 47,XYY XYY syndrome is a condition that is caused by a male having an extra copy of Approximately 1 in syndrome the Y sex chromosome (one copy of the X chromosome and two copies of the 1000 males are born Y chromosome rather than the usual one copy of each). XYY syndrome is likely with XYY syndrome. to result in live birth. Males with XYY syndrome have variable phenotypes. Some of the common features of XYY syndrome include delayed speech and language development and taller stature. There is a slightly increased risk for males with XYY syndrome to have an autism spectrum disorder or learning disability. MICRODELETION SYNDROMES 1p36 1p36 deletion 1p36 deletion syndrome is a genetic syndrome characterized by birth de- 1 in 4,000 to 1 in deletion fects, intellectual disability, and other serious medical issues. 1p36 deletion 10,000 newborns syndrome syndrome is caused by a deletion in the region of 1p36. Key features of this have this condition, syndrome include characteristic craniofacial features, intellectual disability, sei- with a female to zures, skeletal abnormalities, and brain and heart defects. Lifespan is variable male ratio of 2:1. but can be normal. Wolf- 4p16.3 deletion 4p- syndrome is a rare genetic syndrome characterized by birth defects, intel- 1 in 50,000 newborns Hirschhorn lectual disability, and other serious medical problems. 4p- syndrome is caused have this condition, syndrome/ by a deletion in the region of 4p16.3. Key features of the syndrome include with a 2:1 female to 4p- syndrome prenatal-onset growth deficiency followed by postnatal growth retardation male ratio. and hypotonia with muscle underdevelopment, typical craniofacial features in infancy consisting of a characteristic appearance of the nose, microcephaly, intellectual disability of variable degree, seizures, skeletal anomalies, congen- ital heart defects, hearing loss (mostly conductive), urinary tract malforma- tions, and structural brain abnormalities. Life expectancy varies depending on severity of features. Cri-du-Chat 5p15.2 deletion 5p- syndrome is a genetic syndrome characterized by birth defects, intellectual 1 in 20,000 to 1 in syndrome/ disability, and other serious medical issues. 5p- syndrome is caused by a dele- 50,000 live births 5p- syndrome tion in the region of 5p15.2. Key features of this syndrome include significant have this condition. intellectual disability, speech delay, cat-like cry, dysmorphic features, micro- cephaly and 10% mortality in first year. Prader-Willi 15q11.2-q13 Prader-Willi syndrome (PWS) is a rare genetic condition that causes difficulty 1 in 10,000 to 1 in and deletion feeding and failure to thrive in infancy, with obesity, developmental delay, and 25,000 newborns Angelman other medical problems as the child gets older. NIPT is only able to detect have PWS. 1 in syndromes PWS caused by a deletion, which accounts for ~70% of cases; the remaining 12,000 to 1 in 20,000 cases are caused by different underlying molecular mechanisms. Angelman newborns have AS. syndrome (AS) is a rare genetic syndrome that includes intellectual disability and other serious medical problems. NIPT is only able to detect AS caused be a deletion, which accounts for ~68% of cases; the remaining cases are caused by different underlying molecular mechanisms. DiGeorge 22q11.2 deletion 22q11.2 deletion syndrome is a genetic syndrome that is variable in presen- 1 in 4,000 live births syndrome tation. Many features have been reported, yet individuals with this syndrome have this condition. may have different presentations from one another. Key features of this syndrome are variable, but include intellectual disability, heart defects, palatal abnormalities, immune deficiency, and dysmorphic features. Life span is usu- ally normal, but can vary depending on severity of features. References 1. American College of Obstetricians and Gynecologists. Screening for fetal aneuploidy. Practice Bulletin No. 163. Obstet Gynecol. 2016;127:e123-e137. 2. Gardner RJM, Sutherland GR, Schaffer LG. Chromosome Abnormalities and Genetic Counseling. 5th ed. New York, NY: Oxford University Press; 2018. 3. Jones KL. Smith’s Recognizable Patterns of Human Malformation. 6th ed. Philadelphia, PA: W.B. Saunders Company; 2006. 4. Nussbaum RL, McInnes RR, Willard HF. Thompson & Thompson Genetics in Medicine. 7th ed. Philadelphia, PA: Saunders Elsevier; 2007. HEADQUARTERS | 1400 16th Street, San Francisco, CA 94103 | ONLINE | www.invitae.com | CONTACT | www.invitae.com/ contact © 2019 Invitae Corporation. All Rights Reserved. P/N F250-1.