Genetic Disorders and Terms

1p36 deletion syndrome (monosomy 1p36 syndrome) is characterized by a deletion on the short arm of chromosome 1. The disorder is characterized by dysmorphic craniofacial features, developmental delay, brain abnormalities, short feet, congenital heart defects, hypotonia, and brachy/camptodactyly. Most cases are not inherited (de novo). View testing options

Adenosine deaminase (ADA) deficiency is an inherited disease characterized by repeated, persistent, and potentially life-threatening infections. Symptoms are due to a defect in the production of an enzyme called adenosine deaminase. Without normal levels of this enzyme, toxic chemicals build up within the immune system leading to severe immunodeficiency, a state in which the body’s ability to fight infectious disease is absent or severely compromised. The severe form of ADA deficiency is also known as ADA-deficient severe combined immunodeficiency (SCID). View testing options

AFP is a protein produced during pregnancy that can be measured through a blood test once you’re at least 15 weeks pregnant. It can be used to determine the chance of having a baby affected with Down syndrome, trisomy 18 and open neural tube defects.

Alpha-mannosidosis is an inherited disease characterized by developmental delays, facial and skeletal abnormalities, hearing loss, and immune deficiency. It is caused by abnormalities in the enzyme alpha-mannosidase that breaks down small sugar molecules called oligosaccharides. Symptoms associated with alpha-mannosidosis are due to the toxic build-up of oligosaccharides and the progressive destruction of cells, particularly in the central nervous system. View testing options

Performed when you’re between 15 and 21 weeks pregnant, amniocentesis is a procedure to obtain amniotic fluid. The fluid can be tested for chromosomal disorders and open neural tube defects. It can also be used to test for certain genetic disorders such as cystic fibrosis and sickle cell disease, if your pregnancy is determined to be at increased risk for a genetic disorder. It can’t test for the 3-5% of birth defects that are everyone’s background risk.

The procedure involves withdrawing amniotic fluid (the fluid surrounding the developing baby). This fluid contains fetal cells that can be used for chromosome testing. The fluid also contains alpha-fetoprotein (AFP) that is used in testing for open neural tube defects.

An analysis of alpha-fetoprotein in the amniotic fluid to detect open neural tube defects.

Andermann syndrome is an inherited disease characterized by severe progressive damage to the nervous system and absence or malformation of the corpus callosum in the brain. Andermann syndrome involves defects in a transporter protein that is involved in moving potassium (K) and chlorine (Cl) across the cell membrane. Symptoms associated with Andermann syndrome are attributed to the abnormal function of this transporter protein, which is believed to interfere with the development and maintenance of nerve tissue. Other names for Andermann syndrome include hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC); agenesis of the corpus callosum with peripheral neuropathy (ACCPN); Charlevoix disease. View testing options

Anencephaly is a severe form of an open neural tube defect which results in the absence of much (or a major part) of the brain. The neural tube is a structure that develops into a baby’s spinal cord and brain. The tube is open early in the pregnancy and normally closes as the embryo develops. When the tube fails to close properly, it results in an opening. Severity varies depending upon the size and position of the opening.

An open neural tube defect causes a range of disabilities from paralyzed legs to incomplete brain development. Lack of closure above the neck results in anencephaly or encephalocele. Lack of closure below the neck results in spina bifida. Most babies born with an open neural tube defect are born into families with no previous history of open neural tube defects.

Factors that increase the risk for having a child with an open neural tube defect include the pregnant woman:

•  having a close relative who is affected
• having diabetes
• using certain medications

Supplemental use of folic acid prior to and early in the pregnancy significantly decreases the risk of open neural tube defect. View testing options

Both Angelman (AS) and Prader-Willi (PWS) syndromes may be caused by deletions on the long arm of chromosome 15. Maternal deletions lead to AS while paternal deletions result in PWS. Seventy percent of both AS and PWS are caused by deletions on the long arm of chromosome 15. These disorders affect the nervous system and, while both result in developmental delay, each presents with its own unique clinical features. View testing options

Argininosuccinic aciduria (ASA) is an inherited disease characterized by vomiting, liver disease, and intellectual disabilities. It involves defects in an enzyme called argininosuccinate lyase (ASL). This enzyme is important for breaking down nitrogen (found in proteins) so that it does not build up as ammonia. The symptoms of argininosuccinic aciduria are due to the toxic accumulation of ammonia, particularly in the liver and nervous system. Argininosuccinic aciduria is also known as argininosuccinate lyase (ASL) deficiency. View testing options

Individuals whose ancestors are of Eastern European Jewish descent. Their ethnicity can be traced back to countries such as Germany, Hungary, Poland, and Russia.

Aspartylglucosaminuria (AGU) is an inherited disease characterized by progressive intellectual and developmental disabilities and skin, bone, and joint issues. It is caused by defects in the enzyme aspartylglucosaminidase, which is needed to properly break down certain sugars (oligosaccharides) that are attached to specific proteins (glycoproteins). Symptoms associated with aspartylglucosaminuria are attributed to the toxic build-up of glycoproteins in cells, particularly in cells of the central nervous system, leading to progressive destruction of nerve cells in the brain. View testing options

Ataxia-telangiectasia (A-T) is an inherited disease that affects the nervous system, the immune system, and leads to an increased risk of cancer. It involves the absence or reduction of the ATM (ataxia-telangiectasia mutated) protein that is involved in the control of cell division, DNA repair, natural cell death, and other important cell functions. Symptoms associated with ataxia-telangiectasia are due to lack of control in cell growth and DNA repair, which leads to premature cell death or the formation of cancer cells. Ataxia-telangiectasia is also known as Louis-Bar syndrome. View testing options

A disability usually characterized by the abnormal development of communication skills, social skills, and reasoning. The underlying cause of autism is not well understood and prenatal testing for all causes of autism is not available.

Inherited disease for which one parent needs to carry a non-working copy of a gene in order to have an increased chance (50%) to have a baby with the disease. It affects males and females equally. Examples of autosomal dominant conditions include Marfan syndrome, Huntington disease and neurofibromatosis.

Inherited disease for which both parents need to carry a non-working copy of the same gene in order to have an increased chance (25%) to have a baby with the disease. It affects males and females equally. Examples of autosomal recessive conditions include cystic fibrosis, sickle cell disease, and Tay-Sachs disease.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited disease characterized by progressive muscle damage, speech and vision problems. It is caused by defects in sacsin, a protein that may be involved in organizing proteins within cells, especially those of the nervous system and muscles. ARSACS is also known as spastic ataxia of Charlevoix-Saguenay. View testing options

For every 100 babies that are born, 3-5 will have a major birth defect. This 3-5% is known as the background risk.

Bardet-Biedl syndrome (BBS) is an inherited disease characterized by progressive vision loss, obesity, birth defects, learning disabilities, and behavioral problems. The symptoms associated with BBS are likely due to the abnormal functioning of cilia, which are hair-like structures found on the surface of many cells of the body. BBS is also known as Laurence-Moon-Bardet-Biedl syndrome. View testing options

Beta thalassemia is an inherited disease characterized by mild to severe anemia, poor growth, enlargement of the spleen, and skeletal changes. It involves a deficiency of one of the components of hemoglobin, the oxygen-carrying molecule in the blood. Soon after birth, the majority of hemoglobin is comprised of iron and four globin chains, two alpha-globin and two beta-globin chains. Symptoms of beta thalassemia are due to reduced production of the beta-globin chains (b+) or no production of beta-globin chains (b0). This, in turn, results in decreased hemoglobin levels which causes anemia and other associated health problems. Beta thalassemia is also known as Cooley’s anemia and Mediterranean anemia. View testing options

An abnormality that is present at birth (for example, Down syndrome or spina bifida or a heart defect). Birth defects can have many different causes. Not all birth defects can be detected by prenatal testing or ultrasound examination.

Bloom syndrome causes poor growth, poor immune system function, sun sensitivity, and a high rate of cancer. Individuals with Bloom syndrome usually die from cancer before age 30. Bloom syndrome does not affect intelligence. View testing options

A gene on chromosome 17 that normally helps to suppress cell growth. A person who inherits certain mutations (changes) in a BRCA1 gene has a higher risk of getting breast, ovarian, prostate, and other types of cancer. View testing options

A gene on chromosome 13 that normally helps to suppress cell growth. A person who inherits certain mutations (changes) in a BRCA2 gene has a higher risk of getting breast, ovarian, prostate, and other types of cancer. View testing options

Cancer that forms in tissues of the breast. The most common type of breast cancer is ductal carcinoma, which begins in the lining of the milk ducts (thin tubes that carry milk from the lobules of the breast to the nipple). Another type of breast cancer is lobular carcinoma, which begins in the lobules (milk glands) of the breast. Invasive breast cancer is breast cancer that has spread from where it began in the breast ducts or lobules to surrounding normal tissue. Breast cancer occurs in both men and women, although male breast cancer is rare.

Breast cancer markers such as estrogen receptor (ER), progesterone receptor (PR), and HER2 are used to help guide therapy decisions after a diagnosis of breast cancer. They are proteins made by the tumor which can be targeted by specific therapies. Other markers such as Ki67 and p53 also may be used to help determine need for chemotherapy, although they are not specific targets of therapy.

Canavan disease is a disorder which causes brain and nervous system degeneration. Symptoms usually occur within the first few months of life and individuals with Canavan disease usually die in early childhood. There is currently no treatment. View testing options

An individual who has a copy of a disease-causing gene but does not typically have the disease.

Carrier testing determines if a couple is at increased risk of having a baby with a specific inherited disease, such as Tay-Sachs disease or cystic fibrosis.

Cartilage-hair hypoplasia (CHH) is an inherited disease characterized by abnormal bone growth, causing short stature and other skeletal anomalies; blood and immune problems; and fine, sparse, light-colored hair. Symptoms associated with cartilage-hair hypoplasia are due to the disruption of normal cellular function, primarily affecting the skeletal and immune systems. Cartilage-hair hypoplasia belongs to a group of disorders known as cartilage-hair hypoplasia–anauxetic dysplasia (CHH-AD) spectrum disorders, and is also known as McKusick's metaphyseal chondrodysplasia syndrome. View testing options

Performed when you’re between 10 and 12 weeks pregnant, chorionic villi sampling (CVS) is a procedure used to obtain a sample that can be tested for Down syndrome and other chromosomal disorders, as well as certain genetic disorders such as cystic fibrosis and sickle cell disease, if your pregnancy is determined to be at risk for a genetic disorder. CVS can’t test for the 3-5% of birth defects that are everyone’s background risk. The procedure involves taking a small sample of tissue from the developing placenta.

A normal human cell has 46 chromosomes. A missing or an extra chromosome, or piece of a chromosome, interferes with normal development. Many chromosomal abnormalities can lead to serious physical birth defects, intellectual and developmental disabilities or both. The most common chromosome abnormalities are Down syndrome, trisomy 18, and trisomy 13. View testing options

An analysis of the number and structure of chromosomes in a cell. A picture of the chromosomes from a cell arranged in the standard order is called a karyotype.

Citrullinemia type I (CTLN1) is an inherited disease characterized by poor growth, vomiting, spasticity, increased intracranial pressure, and neurologic disorders. It involves defects in an enzyme called argininosuccinate synthase. This enzyme is important for breaking down nitrogen (found in proteins) so that it does not build up as ammonia. The symptoms of CTLN1 are due to the toxic accumulation of ammonia and other substances, particularly in the liver and nervous system. Citrullinemia type I is also known as argininosuccinate synthetase deficiency or citrullinuria. View testing options

A cleft lip is a congenital deformity characterized by failure of the lip tissue to grow normally, leading to a vertical gap or opening in the upper lip.

Cobalamin C disease (cblC), also known as methylmalonic aciduria with homocystinuria, is an inherited disease characterized by hypotonia, lethargy, intellectual and developmental disabilities, seizures, vision problems, and blood-related problems. It involves defects in a protein used to change vitamin B12 into a form that the body uses to break down certain amino acids and fats. Symptoms are due to the build-up of these substances and their metabolites in the body’s organs and tissues. View testing options

Cancer that develops in the colon (the longest part of the large intestine) and/or the rectum (the last several inches of the large intestine before the anus).

A congenital disorder is a defect acquired during fetal development or present at birth. A congenital disorder is not necessarily hereditary.

Congenital disorder of glycosylation type 1a (CDG-1a) is an inherited disease characterized by variable developmental delays and muscle and bone problems that change with age. It involves defects in the enzyme phosphomannomutase 2 (PMM2). This enzyme is important in the cellular process of attaching sugars to proteins (glycosylation). The symptoms of CDG-1a are due to abnormalities in the glycosylation process, which leads to a wide variety of symptoms throughout the body. View testing options

Cri-du-chat (5p minus) is caused by a partial deletion of the short arm of chromosome 5. The disorder is characterized by intellectual disability, developmental delay, microcephaly, hypotonia, distinctive facies, heart defects, and a characteristic cat-like cry. Most cases are not inherited (de novo) but transmission from an unaffected parent carrying a balanced translocation is seen in ~10% of cases. View testing options

Cystic fibrosis is an autosomal recessive disease most common in individuals of Caucasian and Ashkenazi Jewish ancestry, but also occurring in other ethnic groups. Symptoms vary from mild to severe, and include life-threatening lung infections, digestion problems, diarrhea, poor growth and infertility. Average lifespan today is less than 40 years of age. View testing options

Cystinosis is an inherited disease characterized by a type of kidney disease called renal tubular Fanconi syndrome, poor growth, and photophobia (sensitivity to light in the eyes). It involves abnormalities in the protein cystinosin, which moves the amino acid cystine within cells. Symptoms associated with cystinosis are due to a build-up of cystine, which forms crystals within cells throughout the body, resulting in tissue damage. Cystinosis is also known as cystine storage disease. View testing options

D-bifunctional protein (DBP) deficiency is an inherited disease characterized by neonatal low muscle tone, seizures, visual and hearing loss, developmental delays, and death usually by two years of age. DBP deficiency involves defects in the D-bifunctional protein that is involved in the breakdown of a specific type of fatty acids in the body called “very long-chain fatty acids” (VLCFA). The symptoms of DBP deficiency are due to the toxic build up of VLCFA, which causes damage in the cells, especially in the brain and liver. DBP deficiency is also known as peroxisomal bifunctional enzyme deficiency and pseudo-Zellweger syndrome. View testing options

Diagnostic tests indicate if your baby is affected or not affected with a specific birth defect or genetic disease, including Down syndrome. The accuracy of diagnostic testing depends on the test and on the birth defect or genetic disease tested. In contrast, see screening test.

An autosomal dominant condition caused by a submicroscopic deletion of the long arm of chromosome 22. The disorder is characterized by cardiac abnormalities, abnormal facies, thymic aplasia, cleft palate, hypocalcemia (CATCH-22). Most cases are not inherited (de novo) but transmission from a parent carrying the 22q11 deletion is seen in ~7% of cases. View testing options

Dihydropyrimidine dehydrogenase (DPD) deficiency is an inherited disease of variable severity that is typically characterized by the presence of childhood-onset neurological problems. DPD deficiency involves defects in making the enzyme dihydropyrimidine dehydrogenase that is needed to break down uracil and thymine (two of the basic building blocks of RNA and DNA). Symptoms associated with DPD deficiency are a result of the toxic build-up of uracil and thymine in the body. DPD deficiency is also known as dihydropyrimidinuria and familial pyrimidemia. View testing options

Down syndrome, also known as trisomy 21, is a congenital disorder caused by the presence of an extra #21 chromosome. Most cases are not inherited, but family history of Down syndrome can increase the risk. Individuals with Down syndrome have varying degrees of intellectual and developmental disabilities, characteristic physical appearance, as well as physical problems, such as heart defects. View testing options

Cancer that forms in the tissue lining the uterus (the small, hollow, pear-shaped organ in a woman's pelvis in which a fetus develops). Most endometrial cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).

This hormone is the main estrogen produced by the placenta during pregnancy and is measured in a blood test to determine the chance of having a baby affected with Down syndrome or trisomy 18.

Ethylmalonic encephalopathy (EE) is an inherited disease characterized by abnormalities of the nervous system, gastrointestinal tract, and blood vessels. It involves defects in the enzyme ETHE1, which is thought to play an important role in energy production. Symptoms associated with EE are due to reduced energy production in cells and a toxic build-up of metabolites in the body. View testing options

Cancer that occurs in families more often than would be expected by chance. These cancers often occur at an early age, and may indicate the presence of a gene mutation that increases the risk of cancer. They may also be a sign of shared environmental or lifestyle factors.

Familial dysautonomia is a progressive nervous system disorder that causes severe vomiting, decreased pain sensitivity, unstable blood pressure and temperature and frequent pneumonia. Individuals affected with familial dysautonomia often have normal intelligence, but may have learning disabilities. Symptom management improves quality of life, but only 50% of affected individuals will reach age 30. View testing options

Familial hyperinsulinism (FHI) is an inherited disease characterized by hypoglycemia due to unregulated release of insulin from cells in the pancreas. Symptoms are the result of increased levels of insulin in the blood, which causes decreased blood sugar levels (or hypoglycemia). FHI is also known as congenital hyperinsulinism (CHI). View testing options

Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease characterized by episodes of recurrent fever and pain in the abdomen, chest, and joints. Symptoms are attributed to decreased levels of a protein called pyrin (also known as marenostrin), which is involved in the body’s immune response by helping to regulate inflammation. FMF is also known as familial paroxysmal polyserositis. View testing options

Fanconi anemia group C causes anemia, short stature and, often, abnormalities of the heart, kidneys and/or limbs. Some individuals have learning disabilities or intellectual and developmental disabilities. The risk of early childhood cancer, especially leukemia, is increased. View testing options

Fragile X syndrome is the most common cause of inherited intellectual and developmental disabilities, affecting approximately 1 in 4,000 males and 1 in 8,000 females. There may or may not be a family history of intellectual and developmental disabilities. Fragile X syndrome causes a range of symptoms. Early signs include delayed speech and language. Intellectual abilities vary from mild learning disabilities to severe intellectual and developmental disabilities. Behavioral characteristics include autism, hyperactivity and poor eye contact. Physical features, such as a long face and large or prominent ears, are usually more noticeable in adults than in children, and in males more than females. View testing options

Gaucher disease is a variable disease, caused by a particular enzyme deficiency. Children and adults with this condition may have anemia, enlarged liver and spleen, easy bruising, nosebleeds and fractures. The most common form of Gaucher disease, type 1, is treatable by enzyme replacement therapy. In the more severe form, which occurs much less frequently, the brain and nervous system are also involved; this form cannot be treated at this time. View testing options

A “blueprint” of hereditary information passed from parents to their children. An inherited disease (for example, cystic fibrosis) is caused by having non-working or absent genes.

A disease or condition caused by a defective or missing gene, a combination of genetic and environmental factors, or by a chromosome abnormality.

Glutaric acidemia type 1 (GA-1) is an inherited disease characterized by episodes of severe brain dysfunction that result in spasticity, low muscle tone, and seizures. It involves defects in the glutaryl-CoA dehydrogenase enzyme, a protein that breaks down the amino acids lysine, hydroxylysine, and tryptophan. The symptoms of GA-1 are due to the build-up of these amino acids and their metabolites in the body, primarily affecting the brain. Glutaric acidemia type 1 is also known as glutaric aciduria type 1.  View testing options

Glutathione synthetase (GS) deficiency is an inherited disease characterized by anemia with or without neurological problems. It is caused by defects in the enzyme glutathione synthetase, which is important in the production of an antioxidant called glutathione. Glutathione helps to protect cells from damage. Symptoms associated with GS deficiency are due to low levels of glutathione in cells. GS deficiency is also known as 5-oxoprolinuria or pyroglutamic aciduria. View testing options

Glycogen storage disease type 1a causes severe low blood sugar, enlarged liver, bleeding problems and delayed growth. Treatment requires a special diet often including tube feedings at night and/or during illness. View testing options

Glycogen storage disease type I (GSD-I), also called von Gierke disease, is an inherited disease caused by a defect in the body’s ability to break down glycogen (the form in which the body stores sugar) to glucose (a free form of sugar and the body’s main source of energy). Symptoms associated with GSD-I are attributed to low blood glucose levels and excessive storage of glycogen in the liver and kidneys. GSD I occurs in two forms: GSD-Ia and GSD-Ib. GSD-Ib is caused by a deficiency of the enzyme glucose-6-phosphate transporter (G6PT) whose function is to help maintain normal blood glucose levels. View testing options

Glycogen storage disease (GSD) type III, is an inherited disorder typically characterized by liver disease during childhood and slowly progressive muscle weakness in adult years. GSDIII is caused by a defect in the body’s ability to completely break down glycogen (the form in which the body stores sugar) to glucose (a free form of sugar and the body’s main source of energy) due to a deficiency of an enzyme called glycogen debranching enzyme. Symptoms associated with GSDIII are due to excessive accumulation of abnormally formed glycogen—primarily in the liver, skeletal, and heart muscles—as well as low blood glucose levels. View testing options

GRACILE syndrome is an inherited disease characterized by poor fetal growth, iron overload, liver damage, and death in infancy. It involves defects in a protein that research suggests most likely involves energy production in cells and iron metabolism. Symptoms associated with GRACILE syndrome may be attributed, at least in part, to iron accumulation, mainly in the liver. GRACILE syndrome is also known as Fellman syndrome. View testing options

Glycine encephalopathy (GCE) is an inherited disease that in its typical form is characterized by seizures in infancy and other progressive nervous system problems. It is caused by an abnormally low level of an enzyme that helps to break down the amino acid glycine, which is important in brain function. Symptoms are due to a toxic build-up of glycine in the body. Glycine encephalopathy is also known as non-ketotic hyperglycinemia (NKH). View testing options

Human chorionic gonadotropin (hCG) is a hormone produced by the placenta during pregnancy, and is measured in a blood test to determine the chance of having a baby affected with Down syndrome or trisomy 18.

In medicine, describes the passing of genetic information from parent to child through the genes in sperm and egg cells. Also called inherited.

Hereditary fructose intolerance (HFI) is an inherited disease characterized by nausea, abdominal pain, diarrhea, vomiting, low blood sugar, and liver and kidney damage. It involves defects in making the enzyme aldolase B, which is responsible for breaking down fructose (a sugar found primarily in fruit) into a form used by the body for energy. View testing options

HMG-CoA lyase deficiency is an inherited disease characterized by lethargy, vomiting, and low blood sugar. It can quickly progress to breathing problems, seizures, coma, and death if untreated. It involves defects in the production of enzyme 3-hydroxymethyl-3-methylglutaryl-coenzyme A lyase (HMG-Co A lyase), which the body needs to break down fats and proteins to make energy. The symptoms of HMG-CoA lyase deficiency are due to a reduced energy production in cells and a toxic build-up of metabolites in the body leading to cellular damage—particularly in the brain. HMG-CoA lyase deficiency is also known as hydroxymethylglutaric aciduria. View testing options

Holocarboxylase synthetase (HLCS) deficiency is an inherited disease characterized by vomiting, lethargy, developmental delays, and hypotonia when untreated. It involves abnormalities in the enzyme holocarboxylase synthetase, which uses the vitamin biotin for the normal processing of proteins, fats, and carbohydrates. Symptoms are due to the toxic build-up of these substances in the body. Holocarboxylase synthetase deficiency is also called multiple carboxylase deficiency. View testing options

Homocystinuria, CBS-related is an inherited metabolic disease characterized by developmental delays, eye problems, skeletal abnormalities, and increased risk of blood clots. It involves abnormalities in the enzyme cystathionine beta-synthase (CBS) that breaks down the amino acid homocysteine. Symptoms are believed to be due to the toxic build-up of homocysteine and its metabolites in the body. Homocystinuria, CBS-related is also referred to as “classical homocystinuria.” View testing options

A technology in which an egg is fertilized in a laboratory and then transferred into the uterus.

The inability to become pregnant or carry a pregnancy to term after persistent attempts over a given period of time. Either men or women can be the cause of infertility.

Humans have over 30,000 individual genes that come in pairs. An inherited disease is passed from parents to child and is caused by a mutation in a gene. Tay-Sachs disease and cystic fibrosis are examples of inherited diseases that can be tested for. View testing options

Inhibin is a hormone measured in a blood test to determine the chance of having a baby affected with Down syndrome or trisomy 18.

Jacobsen syndrome is caused by a deletion in the long arm of chromosome 11. It is characterized by developmental delay, distinctive facies, bleeding disorders and some behavior disorders. Most cases are not inherited (de novo). View testing options

Joubert syndrome 2 (JBTS2) is an inherited disease characterized by brain malformations, developmental delay, low muscle tone, and breathing abnormalities. Signs and symptoms of JBTS2 are thought to be caused by the abnormal functioning of cilia, which are hair-like structures found on the surface of all cells of the body. JBTS2 is also known as cerebello-oculo-renal syndrome 2 (CORS2). View testing options

Junctional epidermolysis bullosa (JEB) is an inherited skin disease caused by abnormalities in proteins that hold layers of the skin together. Symptoms associated with JEB are attributed to defects in the growth, movement, and attachment of skin cells. View testing options

A picture of the chromosomes from a cell arranged in the standard order.

Klinefelter syndrome (47XXY or XY/XXY mosaic) with male phenotype is the most pervasive sex chromosomal anomaly (26) affecting approximately 1:600 males. (27) Males with Klinefelter syndrome carry two or more X chromosomes which results in abnormal development of the testis, leading to hypogonadism and infertility. (28) Affected individuals are often tall and produce relatively small amounts of testosterone. As a result of this hormone imbalance, affected males have incompletely developed secondary male sex characteristics.View testing options

Krabbe disease is an inherited disorder characterized by progressive muscle weakness and stiffness, feeding problems, slowed mental and physical development, vision loss, and seizures. It involves a deficiency in the enzyme galactocerebrosidase (GALC), which is important in the growth and maintenance of myelin, the protective covering around nerve cells. The symptoms of Krabbe disease are due to the abnormal breakdown of myelin and the build-up of toxic byproducts in the body. Krabbe disease is also known as galactocerebrosidase deficiency and globoid cell leukodystrophy. View testing options

Langer-Giedion syndrome is caused by a deletion to the long arm of chromosome 8. It is characterized by benign bone tumors (exostoses), short stature, and distinctive facial features. Most cases are not inherited (de novo). View testing options

Leigh syndrome, French Canadian type (LSFC) is an inherited disease characterized by developmental delays, low muscle tone, distinctive facial features, and severe episodes of illness that can lead to early death. It is caused by defects in a protein that affects the levels of an enzyme, called COX, which is crucial for energy production in cells. Symptoms are believed to be due to low levels of the COX enzyme, leading to abnormal energy production in the cells and (ultimately) cell death, especially in the nervous system and liver. LSFC is also known as COX deficiency, French Canadian type. View testing options

Long-chain 3-hydroxyacyl-coA dehydrogenase (LCHAD) deficiency is an inherited disease characterized by lethargy, weakness, vomiting, and low blood sugar. It can quickly progress to liver problems, seizures, coma, and death if untreated. LCHAD deficiency involves abnormalities in an enzyme involved in the breakdown of long-chain fatty acids that are used for energy in cells. Symptoms associated with LCHAD deficiency are due to low levels of energy and the toxic build-up of fatty acids in cells, especially in the liver and brain. View testing options

Lynch Syndrome - also known as hereditary non-polyposis colorectal cancer (HNPCC) - is a rare, inherited form of colon cancer that arises from mutations in DNA mismatch repair genes. Under normal conditions, DNA mismatch repair proteins repair mistakes in DNA. Lynch Syndrome is sometimes associated with other forms of cancer, including endometrial, ovarian, pancreas, stomach, small bowel, biliary, and urinary tract carcinomas.

Maple syrup urine disease (MSUD) causes certain amino acids to accumulate in the blood. The disease name refers to the characteristic smell of the urine. Without early diagnosis and treatment, classic MSUD leads to intellectual and developmental disabilities, physical disabilities, seizures and death. Treatment, which consists of a strict, lifelong special diet, may help to control the accumulation of amino acids in the blood and may improve the symptoms. View testing options

Cells from the mother. These cells may be mixed in with the fetal sample and can interfere with the results.

Maternal serum screening tests (see also screening test). A group of tests that measure proteins and hormones in your blood during pregnancy to determine the chance of having a baby affected with Down Syndrome, trisomy 18 or open neural tube defects.

Screen Positive Screening test results showing anincreased riskof having an affected baby. Your doctor will offer diagnostic testing to determine if your baby is affected with one of these birth defects.

Screen Negative Screening test results showing alow riskof having an affected baby. But, these screening tests don’t detect all affected pregnancies.

Performed when you’re between 15 and 20 weeks pregnant, maternal serum-alpha-fetoprotein (MSAFP) screening is a blood test to determine the chance of having a baby affected with anopen neural tube defect.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inherited metabolic disease characterized by lethargy, vomiting, and low blood sugar triggered by fasting or common illness. It can quickly progress to liver problems, seizures, coma, and death, if untreated. MCAD deficiency involves abnormalities in an enzyme involved in the break down of medium-chain fatty acids that are used for energy in the cells. Symptoms associated with MCAD deficiency are due to low levels of energy in cells and the toxic build-up of fatty acids, which causes damage to the cells, especially in the liver and brain. View testing options 

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

Metachromatic leukodystrophy (MLD) is an inherited disease with a variable age of onset and is characterized by the progressive loss of motor skills and intellectual function. It involves defects in the enzyme called arylsulfatase A (ARSA), which breaks down molecules called sulfatides (a type of lipid found in cell membranes), particularly within the nervous system. Symptoms associated with MLD are due to the build-up of sulfatides that destroy myelin (the protective material that surrounds nerve cells). Metachromatic leukodystrophy is also known as arylsulfatase A deficiency. View testing options

Methylmalonic acidemias are a group of inherited diseases characterized by lethargy, vomiting, developmental delays, hypotonia, and enlargement of the liver. They involve defects in one of several proteins and enzymes that break down certain amino acids, fatty acids, and cholesterol in the body. Symptoms are due to the toxic build-up of these substances and their metabolites in organs and tissues. Subtypes include cobalamin A type, cobalamin B type, and methylmalonyl CoA mutase deficiency. View testing options

Mucolipidosis type IV affects the brain and nervous system. Symptoms begin in the first year of life, and affected individuals have delayed developmental milestones, intellectual and developmental disabilities and progressively worsening vision. There is currently no treatment. View testing options 

Mucopolysaccharidosis type I (MPS I) is an inherited disease characterized by developmental delays, distinctive facial features, enlarged organs, and skeletal and joint abnormalities. It involves abnormalities in the enzyme α-L-iduronidase, which breaks down large sugars (known as glycosaminoglycans or mucopolysaccharides). The symptoms of MPS I are due to the build-up of mucopolysaccharides within cells. Mucopolysaccharidosis type I is also known as Hurler syndrome (MPS IH), Hurler-Scheie syndrome (MPS I H/S), or Scheie syndrome (MPS I S). View testing options

A change in a gene. In the context of medical genetics, mutations are disease-causing.

Nemaline myopathy (NM) is an inherited neuromuscular disease characterized by muscle weakness and the presence of rod-shaped structures, known as nemaline bodies, in affected muscle fibers. NM involves defects in the organization and function of components of muscle fibers that are involved in muscle contraction. The inability of the muscles to contract properly results in muscle weakness and other symptoms. View testing options

Nephrotic syndrome, NPHS1-related is an inherited disorder characterized by progressive kidney disease. It is caused by a defect in the production of a protein called nephrin that is essential for normal kidney function. Symptoms associated with nephrotic syndrome type 1 are attributed to the kidney’s inability to maintain normal blood protein levels. Nephrotic syndrome, NPHS1-related is also known as Finnish Congenital Nephrosis. View testing options

Nephrotic syndrome, NPHS2-related is an inherited disease typically characterized by progressive kidney disease in childhood which is resistant to treatment with steroids. It is caused by a defect in the production of a protein called podocin that is essential for normal kidney function. Symptoms associated with nephrotic syndrome, NPHS2-related are attributed to the kidney’s inability to maintain normal blood protein levels. View testing options

The neuronal ceroid-lipofuscinoses (NCLs) are a group of inherited diseases characterized by deterioration of intellectual and motor abilities, seizures, vision loss, and decreased life expectancy. They involve defects in a variety of enzymes responsible for breaking down or moving substances, called lipofuscins, within cells. Symptoms associated with the NCLs are due to a toxic build-up of lipofuscins in the cells and tissues of the body, particularly in the brain. Some of the more common names for forms of this disease include Batten disease, Santavuori-Haltia disease, and Jansky-Bielschowsky disease. View testing options

Niemann-Pick disease type A causes poor growth, enlarged liver, and mental and physical deterioration. Individuals with Neimann-Pick disease type A usually die by age 4. There is currently no treatment. View testing options

Niemann-Pick disease type C (NPC) is an inherited disease caused by an inability of the body to properly move cholesterol and lipids within cells. Symptoms of NPC are caused by the accumulation of cholesterol and lipids, primarily in the liver and brain. NPC belongs to a group of diseases called lysosomal storage disorders. This group includes Niemann-Pick types A and B, which are genetically and clinically distinct. View testing options

Nijmegen breakage syndrome (NBS) is an inherited disease characterized by significant small head circumference from birth (or shortly after), short stature, distinct facial features, recurrent respiratory infections, progressive intellectual disability, decreased fertility in females, and increased cancer risk. The symptoms of NBS are caused by defects in a protein called Nibrin that is involved in repairing damaged DNA as well as in regulating cell creation and growth. NBS is also known as ataxia-telangiectasia variant 1, Berlin breakage syndrome, and Seemanova syndrome. View testing options

Noninvasive prenatal screening (NIPS/NIPT) is a test that uses a maternal blood sample to screen for chromosomal abnormalities, such as trisomy 21 (Down syndrome), in a developing baby.

A nuchal translucency is an ultrasound measurement of the fluid that collects behind the fetus’ neck between 10 and 13 weeks. More fluid indicates a greater risk of an abnormality.

The neural tube is a structure that develops into a baby’s spinal cord and brain. The tube is open early in the pregnancy and normally closes as the embryo develops. When the tube fails to close properly, it results in an opening. Severity varies depending upon the size and position of the opening.

An open neural tube defect causes a range of disabilities from paralyzed legs to incomplete brain development. Lack of closure above the neck results in anencephaly or encephalocele. Lack of closure below the neck results in spina bifida. Most babies born with an open neural tube defect are born into families with no previous history of open neural tube defects. However, the risk for having a child with an open neural tube defect is increased:

• if a close relative is affected
• if there is a history of diabetes in the birth mother
• with the use of certain medications

Supplemental use of folic acid prior to and early in the pregnancy significantly decreases the risk of an open neural tube defect. View testing options

Cancer that forms in tissues of the ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial cancers (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells). Fallopian tube cancer and primary peritoneal cancer are similar to ovarian epithelial cancer and are staged and treated the same way.

A disease in which malignant (cancer) cells are found in the tissues of the pancreas. Also called exocrine cancer.

Pregnancy-Associated Plasma Protein A is a protein that is measured in a blood test to determine the chance of having a baby affected with Down syndrome or trisomy 18.

An obstetrician specializing in perinatology (the anatomy, physiology, diagnosis and treatment of disorders of the mother and the fetus or newborn baby).

Phenylalanine hydroxylase (PAH) deficiency is an inherited disease of variable severity. When untreated, the most severe form of PAH, called phenylketonuria (PKU), is characterized by microcephaly, epilepsy, severe intellectual and developmental disabilities, and behavioral problems. It involves defects in the enzyme phenylalanine hydroxylase, which is responsible for the breakdown of phenylalanine, one of the essential amino acids that is found in a variety of foods, including proteins and some artificial sweeteners. Major symptoms associated with PAH are due to the build-up of phenylalanine to toxic levels in the body, particularly affecting the brain. View testing options

The sac-shaped organ that provides nutrients to the embryo or fetus during pregnancy.

Polycystic kidney disease, autosomal recessive (ARPKD) is an inherited disease that appears to be caused by a defect in the protein fibrocystin, which is essential for kidney and liver function. View testing options

Pompe disease is an inherited disorder characterized by muscle weakness, respiratory insufficiency and, in some forms, enlargement of the heart. It involves deficiency of the enzyme acid α-glucosidase, which normally breaks down glycogen (stored sugar in the body). Symptoms associated with Pompe disease are due to the build-up of toxic levels of glycogen in cells, mainly affecting the heart, skeletal, and respiratory systems. Pompe disease is also known as acid maltase deficiency or glycogen storage disease type II. View testing options

Both Angelman (AS) and Prader-Willi (PWS) syndromes may be caused by deletions on the long arm of chromosome 15. Maternal deletions lead to AS while paternal deletions result in PWS. Seventy percent of both AS and PWS are caused by deletions on the long arm of chromosome 15. These disorders affect the nervous system and, while both result in developmental delay, each presents with its own unique clinical features. View testing options 

Preimplantation Genetic Screening (PGS) is a procedure that screens embryos for certain genetic abnormalities prior to transfer into a woman’s uterus.

Premature Ovarian Failure (POF) is the loss of function of the ovaries before age 40. One result of this condition is infertility. POF is not the same as menopause. See also Primary Ovarian Failure.

Primary amenorrhoea (menstruation cycles never starting) may be caused by developmental problems such as the congenital absence of the uterus, or failure of the ovary to receive or maintain egg cells. Also, delay in pubertal development will lead to primary amenorrhoea. See also Premature Ovarian Failure.

Propionic acidemia (PA) is an inherited disease characterized by vomiting, lethargy, developmental delays, and hypotonia. It involves abnormalities in an enzyme, propionyl-CoA carboxylase, which breaks down proteins and certain types of fats and cholesterol. Symptoms associated with PA are due to a toxic build-up of these substances and their metabolites in the body, primarily affecting the brain and nervous system. View testing options

Propionic acidemia (PA) is an inherited disease characterized by vomiting, lethargy, developmental delays, and hypotonia. It involves abnormalities in an enzyme, propionyl-CoA carboxylase, which breaks down proteins and certain types of fats and cholesterol. Symptoms associated with PA are due to a toxic build-up of these substances and their metabolites in the body, primarily affecting the brain and nervous system. View testing options

Recurrent pregnancy loss is medically defined by 2 or more miscarriages at any stage during pregnancy.

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is an inherited disease characterized by skeletal abnormalities, growth retardation, intellectual disabilities, cataracts and decreased life expectancy. The signs and symptoms associated with RCDP1 are attributed to a defect in the body’s ability to produce a specific type of fat called plasmalogens which are necessary for normal neurological function and skeletal formation. View testing options

Salla disease (SD) is an inherited disorder characterized by progressive damage to the nervous system, poor growth, and seizures. It involves defects in a protein called sialin, which is needed to move a substance called free sialic acid within cells. Symptoms are due to the toxic build-up of sialic acid in the cells, particularly in the nervous system. Salla disease is the mildest form in a group of diseases called sialic acid storage disorders. There is a moderate form called intermediate severe Salla disease and a severe form known as infantile free sialic acid-storage disease (ISSD). View testing options

Sandhoff disease is an inherited disorder characterized by the progressive degeneration of nerve cells in the brain and spinal cord. It involves defects in the enzymes beta-hexosaminidase A and B, which are responsible for breaking down a fatty substance called GM2 ganglioside in the body. Without this enzyme, GM2 accumulates primarily in the brain and nerve cells, causing severe damage. View testing options

Some screening tests are performed during pregnancy and others can be done before or during pregnancy. They can identify your chances of having a baby with disorders such as Down syndrome and cystic fibrosis. Maternal serum screening tests use a blood sample from the mother to identify pregnancies at risk for certain birth defects (in contrast, see also diagnostic test.)

Sex chromosome aneuploidies are syndromes that arise due to carriage of an atypical number of X and/or Y-chromosomes beyond the typical female (XX) or male (XY) complement. Examples include Klinefelter syndrome and XXY aneuploidy.

Sickle cell disease is an autosomal recessive blood disorder that is more common in individuals of African descent, Caribbean descent, Middle Eastern countries, Mediterranean countries (including Turkey, Greece, and Italy), and India. Individuals with sickle cell disease usually have anemia, increased risk of infections and can be affected with “sickle cell crisis”, causing fever, pain, jaundice and other health complications. View testing options

Sjögren-Larsson syndrome (SLS) is an inherited disease characterized by an inability of the body to breakdown certain molecules called fatty aldehydes and fatty alcohols due to a deficiency in the activity of an enzyme called fatty aldehyde dehydrogenase (FALDH). Symptoms associated with SLS are attributed to the accumulation of fatty aldehydes and fatty alcohols in various tissues in the body. SLS is also known as fatty aldehyde dehydrogenase deficiency. View testing options

Smith-Lemli-Opitz syndrome (SLOS) is an inherited disease characterized by multiple birth defects and intellectual and developmental disabilities. Symptoms of SLOS are attributed to the body’s inability to produce cholesterol due to a deficiency of an enzyme called 7-dehydrocholesterol reductase (7-DHC). In pregnancy, cholesterol production is essential for normal development of a baby since it is a component of most cells and is used in the production of certain hormones and digestive acids. View testing options

Spina Bifida is an open neural tube defect, resulting in an incomplete closure of the spinal column. Damage to the exposed spinal cord can cause neurological abnormalities, including paralysis. The neural tube is a structure that develops into a baby’s spinal cord and brain. The tube is open early in the pregnancy and normally closes as the embryo develops. When the tube fails to close properly, it results in an opening. Severity varies depending upon the size and position of the opening.

An open neural tube defect causes a range of disabilities from paralyzed legs to incomplete brain development. Lack of closure above the neck results in anencephaly or encephalocele. Lack of closure below the neck results in spina bifida. Most babies born with an open neural tube defect are born into families with no previous history of open neural tube defects. However, the risk for having a child with an open neural tube defect is increased:

•if a close relative is affected

•if there is a history of diabetes in the birth mother

•with the use of certain medications

Supplemental use of folic acid prior to and early in the pregnancy significantly decreases the risk of open neural tube defects. View testing options

Spinal muscular atrophy (SMA) destroys the nerves responsible for controlling voluntary muscle movement, but does not affect intelligence. Muscles that control breathing, swallowing, head and neck control, walking, and crawling are the most severely affected. Symptoms most often appear before a baby is two years old, but can start before birth or not until adulthood. Over 60% of individuals who are diagnosed with SMA are severely affected. View testing options

The sulfate transporter-related osteochondrodysplasias (STROs) are a group of inherited diseases characterized by short stature and short limbs, spine and joint abnormalities, and early-onset osteoarthritis. The STROs involves abnormalities in a protein that transports sulfate into cells where it is needed for the development of cartilage. The symptoms of STRO are due to the abnormal formation of cartilage and its conversion to bone. The four types of STRO are known as recessive multiple epiphyseal dysplasia, diastrophic dysplasia, atelosteogenesis type 2 (also known as de la Chapelle dysplasia or McAlister dysplasia), and achondrogenesis type 1B. View testing options 

Tay-Sachs disease is an autosomal recessive disease most common in individuals of Eastern European Jewish, French Canadian, or Cajun descent. Tay-Sachs disease causes deterioration in both mental and physical abilities. Individuals with Tay-Sachs disease usually die by age 5. A less common form affects adults rather than children. At this time there is no treatment for Tay-Sachs disease. View testing options

Women with three X chromosomes (47XXX) experience normal development of sexual traits and are fertile. Affected individuals are usually taller than average and have slender builds. The frequency of women obtaining an extra X chromosome is approximately 1:1000. There is no severe phenotype associated with three X chromosomes in women. (25) These women may have slight learning difficulties. View testing options

Trisomy 13 is a congenital disorder caused by the presence of an extra #13 chromosome, occurring in about 1 out of 10,000 live births. Trisomy 13 is always fatal, with more than 80% of babies dying in the first month. The disorder is characterized by profound intellectual and developmental disabilities, cardiac problems, and multiple deformities. View testing options

Full trisomy 16 is not compatible with life and is the most common cause of miscarriage. Mosaic trisomy 16 may present with intrauterine growth retardation, developmental delay, and congenital heart defects. Most frequent cause of spontaneous miscarriage and IUFD. View testing options

Trisomy 18 is a congenital disorder caused by the presence of an extra #18 chromosome, occurring in about 1 out of 3,000 to 1 out of 6,000 live births. Trisomy 18 is always fatal, with 50% of babies dying within the first week and an additional 40% dying within the first year. The disorder is characterized by profound intellectual and developmental disabilities, heart defects, and central nervous system defects. View testing options

Trisomy 21, also known as Down syndrome, is a congenital disorder, caused by the presence of an extra #21 chromosome, in which the affected person has mild to moderate intellectual and developmental disabilities, characteristic physical appearance, and often has physical problems, such as heart defects. View testing options

Full trisomy 22 is rarely compatible with life and most individuals die before birth or shortly after. Mosaic trisomy 22 may present with growth retardation, malformations of the head and face, cardiac abnormalities, and developmental delay. View testing options

This disorder, also referred to as monosomy X (45X) occurs in individuals that have one X chromosome, no Y chromosome, and are phenotypically female. Although 45X is a frequent chromosomal anomaly, Turner syndrome is rare with a live-birth frequency of 1:3000, (23) as only 1 in 40 affected zygotes develops to term. (24) Affected individuals experience abnormal growth patterns, are short in stature, generally lack prominent female secondary sexual characteristics and are sterile. In some instances of Turner syndrome, there are slight intellectual and developmental disabilities. View testing options

This hormone is the main estrogen produced by the placenta during pregnancy. It is measured in a blood test to determine the chances of having a baby affected with Down syndrome or trisomy 18.

An ultrasound (or sonogram) is a technology that uses sound waves to show images of the developing baby. The procedure may be done transvaginally or transabdominally. There are no known risks associated with ultrasound.

Usher syndrome is an inherited disease characterized by hearing loss and progressive vision loss. Damaged proteins are unable to maintain healthy cells in the ear, important for both hearing and balance, and healthy cells in the eyes important for sight. Researchers have divided Usher syndrome into three types (and further subtypes) depending on the age of onset and severity of symptoms. The different Usher syndromes are caused by different damaged proteins and may have varying severity. View testing options

A variation in a genetic sequence whose association with disease risk is unknown. Also called unclassified variant, variant of uncertain significance, and variant of unknown significance.

Walker-Warburg syndrome (WWS), FKTN-related is an inherited disease characterized by muscle, brain, and eye abnormalities. It involves defects in the protein fukutin, which is believed to add chains of sugars to proteins involved in connecting the internal and external structure of cells, protecting muscle fibers, and development of the nervous system. The symptoms are due to abnormal cell structure and function, particularly in the brain, eyes, and muscles. WWS, FKTN-related is the most severe disease within a group of inherited muscle disorders known as alpha-dystroglycanopathies. WWS, FKTN-related is also known as muscular dystrophy-dystroglycanopathy, type A4. View testing options

Wilson disease (WD) is an inherited disorder characterized by liver disease, movement disorders, and psychiatric problems. It involves abnormalities in a protein that removes excess copper from the body. The symptoms associated with WD are due to the build-up of excess copper in the liver, brain, and other tissues. Wilson disease is also known as hepatolenticular degeneration. View testing options

Inherited disease for which the mother has to carry a non-working copy of a gene in order to have an increased chance (50%) to have a son with the disease. Examples of X-linked recessive conditions include Duchenne muscular dystrophy and hemophilia. Rarely, X-linked diseases may affect females as well as males, such as fragile X syndrome.

Men inheriting an additional Y chromosome are usually taller than average and are prone to acne because they produce higher than average levels of testosterone. Affected males are typically fertile and many are unaware that they have a chromosomal abnormality. The frequency of males born with an additional Y chromosome is approximately 1:1000 View testing options

Zellweger syndrome spectrum (ZSS) is a group of inherited diseases that includes Zellweger syndrome, neonatal adenoleukodystrophy (NALD), and infantile Refsum disease (IRD). While initially thought to be distinct disorders, these conditions are now known to be part of the same disease spectrum and share similar symptoms but vary in severity. Zellweger syndrome spectrum is characterized by progressive neurological disease, liver and kidney disease, and hearing and vision loss. The symptoms of ZSS are due to a defect in the body’s ability to produce peroxisomes. Peroxisomes are structures found in almost every cell of the body and are essential for normal brain and nervous system development as well as normal eye, liver, kidney, and bone functions. View testing options