Brachmann de Lange syndrome; CDLS; De Lange syndrome; Typus degenerativus amstelodamensisBrachmann de Lange syndrome; CDLS; De Lange syndrome; Typus degenerativus amstelodamensis
Cornelia de Lange syndrome (CdLS) is a developmental disorder that affects many parts of the body. The severity of the condition and the associated signs and symptoms can vary widely, but may include distinctive facial characteristics, growth delays, intellectual disability and limb defects. Approximately 60% of people affected by CdLS have a disease-causing variation in the NIPBL gene, and about 10% of cases are caused by genetic changes in one of four known genes: SMC1A, SMC3, HDAC8 and RAD21. In the remaining 30% of cases, the underlying genetic cause of the condition is unknown. CdLS can be inherited in an autosomal dominant (NIPBL, SMC2, or RAD21) or X-linked (SMC1A or HDAC8) manner. However, most cases result from new (de novo) genetic changes and occur in people with no family history of the condition.
Estimated Number of People with this Disease
In the U.S., this disease is estimated to be fewer than
5,000
What Information Does GARD Have For This Disease?
Many rare diseases have limited information. Currently GARD is able to provide the following information for this disease:
*Data may be currently unavailable to GARD at this time.
The most common ages for symptoms of a disease to begin is called age of onset. Age of onset can vary for different diseases and may be used by a doctor to determine the diagnosis. For some diseases, symptoms may begin in a single age range or several age ranges. For other diseases, symptoms may begin any time during a person's life.
Prenatal Selected
Before Birth
Newborn Selected
Birth-4 weeks
Infant
1-23 months
Child
2-11 years
Adolescent
12-18 years
Adult
19-65 years
Older Adult
65+ years
The common ages for symptoms to begin in this disease are shown above by the colored icon(s).
Symptoms
These symptoms may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom. This disease might cause these symptoms:
99 Symptoms
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Medical Term
Abnormally low-pitched voice
Frequency
Uncommon
Very frequent
Always
Description
An abnormally low-pitched voice.
An abnormally low-pitched voice.
99 Symptoms
Causes
Genetic Disease
Cornelia de Lange syndrome is a genetic disease, which means that it is caused by one or more genes not working correctly.
Disease causing variants in the following gene(s) are known to cause this disease: SMC1A, NIPBL, SMC3, HDAC8, RAD21, BRD4
Questions:
Questions:
What is a gene?
Genes are part of our DNA, the basic genetic material found in each of our body's cells. Cells are the building blocks of all living things and specialized cells form our body's organs and tissues. DNA is found in the nucleus of a cell and, in humans, is packaged into 23 pairs of chromosomes with the help of special proteins.
Each gene performs a different job in our cells. Some genes serve as the instructions to make proteins. Proteins are needed for the structure, function, and regulation of the body's cells, tissues, and organs. Some genes can turn other genes on or off. Others make RNA molecules that are involved in chemical reactions in the body.
Sources to Learn More: What is a gene? (MedlinePlus) ; What's a Gene? (NHGRI) ; What are proteins and what do they do? (MedlinePlus)Genes are part of our DNA, the basic genetic material found in each of our body's cells. Cells are the building blocks of all living things and specialized cells form our body's organs and tissues. DNA is found in the nucleus of a cell and, in humans, is packaged into 23 pairs of chromosomes with the help of special proteins.
Each gene performs a different job in our cells. Some genes serve as the instructions to make proteins. Proteins are needed for the structure, function, and regulation of the body's cells, tissues, and organs. Some genes can turn other genes on or off. Others make RNA molecules that are involved in chemical reactions in the body.
A genetic variant is a change in a gene's code or DNA sequence that causes the gene to be different than found in most people. A benign variant does not cause health problems or disease because the change does not affect how the gene works. A pathogenic variant does cause health problems or disease because the change does affect how the gene works. A pathogenic variant may also be called a mutation or a disease-causing variant.
Variants can result from DNA copying mistakes made during cell division or certain environmental exposures. Variants that occur in the egg or sperm (germline mutations) can be passed on to offspring, while variants that occur in other body cells (somatic mutations) are not passed on.
Variants can result from DNA copying mistakes made during cell division or certain environmental exposures. Variants that occur in the egg or sperm (germline mutations) can be passed on to offspring, while variants that occur in other body cells (somatic mutations) are not passed on.
A genetic disease is a disease caused by a change in part of a person's DNA. Genetic diseases may be caused by genetic changes in a single gene, in multiple genes, by a combination of genetic changes and environmental factors (multifactorial inheritance), or changes in chromosomes.
Genetic diseases may be caused by genetic changes that are inherited from the parents and are present at birth, like sickle cell disease. Other genetic diseases present at birth may be caused by random genetic changes that happen while the egg or the sperm is forming or soon after fertilization.
Some diseases, like many cancers, are caused by genetic changes that happen during a person's life. These are known as acquired or somatic cell genetic changes. Such genetic changes are not inherited from a parent, but happen either randomly or due to some environmental exposure (such as cigarette smoke).
Sources to Learn More: Genetic Disorders (MedlinePlus) ; Genetic Disorders (NHGRI)A genetic disease is a disease caused by a change in part of a person's DNA. Genetic diseases may be caused by genetic changes in a single gene, in multiple genes, by a combination of genetic changes and environmental factors (multifactorial inheritance), or changes in chromosomes.
Genetic diseases may be caused by genetic changes that are inherited from the parents and are present at birth, like sickle cell disease. Other genetic diseases present at birth may be caused by random genetic changes that happen while the egg or the sperm is forming or soon after fertilization.
Some diseases, like many cancers, are caused by genetic changes that happen during a person's life. These are known as acquired or somatic cell genetic changes. Such genetic changes are not inherited from a parent, but happen either randomly or due to some environmental exposure (such as cigarette smoke).
All individuals inherit two copies of most genes. The number of copies of a gene that need to have a disease-causing variant affects the way a disease is inherited. This disease is inherited in the following pattern(s):
Questions:
Autosomal dominant inheritance
Autosomal means the gene is located on any chromosome except the X or Y chromosomes (sex chromosomes). Genes, like chromosomes, usually come in pairs. Dominant means that only one copy of the responsible gene (causal gene) must have a disease-causing change (pathogenic variant) in order for a person to have the disease. Mutation is an older term that is still sometimes used to mean pathogenic variant.
In some cases, a person inherits the pathogenic variant from a parent who has the genetic disease. In other cases, the disease occurs because of a new pathogenic variant (de novo) in the causal gene and there is no family history of the disease.
Each child of an individual with an autosomal dominant disease has a 50% (1 in 2) chance of inheriting the variant and the disease. Typically, children who inherit a dominant variant will have the disease, but they may be more or less severely impacted than their parent. Sometimes a person may have a pathogenic variant for an autosomal dominant disease and show no signs or symptoms of the disease.Autosomal means the gene is located on any chromosome except the X or Y chromosomes (sex chromosomes). Genes, like chromosomes, usually come in pairs. Dominant means that only one copy of the responsible gene (causal gene) must have a disease-causing change (pathogenic variant) in order for a person to have the disease. Mutation is an older term that is still sometimes used to mean pathogenic variant.
In some cases, a person inherits the pathogenic variant from a parent who has the genetic disease. In other cases, the disease occurs because of a new pathogenic variant (de novo) in the causal gene and there is no family history of the disease.
Each child of an individual with an autosomal dominant disease has a 50% (1 in 2) chance of inheriting the variant and the disease. Typically, children who inherit a dominant variant will have the disease, but they may be more or less severely impacted than their parent. Sometimes a person may have a pathogenic variant for an autosomal dominant disease and show no signs or symptoms of the disease.
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X-linked recessive inheritance
X-linked means the gene is located on the X chromosome, one of two sex chromosomes. Genes, like chromosomes, usually come in pairs. Recessive means that when there are two copies of the responsible gene, both copies must have a disease-causing change (pathogenic variant) in order for a person to have the disease. Mutation is an older term that is still sometimes used to mean pathogenic variant.
Because women have two X chromosomes, a pathogenic variant for an X-lined recessive disease generally needs to occur in both copies of the gene to cause the disease. Because men have one X chromosome and thus only one copy of the gene, a pathogenic variant in their one copy is enough to cause the disease. Women who have a pathogenic variant in one copy of the gene, are called carriers. In rare cases, women carriers may experience mild to moderate symptoms but most have no symptoms.
A woman who carries one X-linked gene variant has a 50% (1 in 2) chance of having a son with the disease and a 50% (1 in 2) chance of having a daughter who is a carrier. A man with an X-linked recessive disease cannot pass on the disease to his sons, but all of his daughters will be carriers. If a male child is the first person in a family with the disease, the pathogenic variant may have been inherited from the mother or may have occurred by chance for the first time in the child (de novo).X-linked means the gene is located on the X chromosome, one of two sex chromosomes. Genes, like chromosomes, usually come in pairs. Recessive means that when there are two copies of the responsible gene, both copies must have a disease-causing change (pathogenic variant) in order for a person to have the disease. Mutation is an older term that is still sometimes used to mean pathogenic variant.
Because women have two X chromosomes, a pathogenic variant for an X-lined recessive disease generally needs to occur in both copies of the gene to cause the disease. Because men have one X chromosome and thus only one copy of the gene, a pathogenic variant in their one copy is enough to cause the disease. Women who have a pathogenic variant in one copy of the gene, are called carriers. In rare cases, women carriers may experience mild to moderate symptoms but most have no symptoms.
A woman who carries one X-linked gene variant has a 50% (1 in 2) chance of having a son with the disease and a 50% (1 in 2) chance of having a daughter who is a carrier. A man with an X-linked recessive disease cannot pass on the disease to his sons, but all of his daughters will be carriers. If a male child is the first person in a family with the disease, the pathogenic variant may have been inherited from the mother or may have occurred by chance for the first time in the child (de novo).
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X-linked inheritance
X-linked means the gene is located on the X chromosome, one of two sex chromosomes. Genes, like chromosomes, usually come in pairs. X-linked diseases are caused by disease-causing (pathogenic) variants in genes on the X chromosome. Mutation is an older term that is still sometimes used to mean pathogenic variant.
The inheritance pattern of many X-linked diseases is not clearly dominant or recessive and so the pattern may be stated as X-linked inheritance. Because men have only one copy of genes on the X chromosome, a pathogenic variant in one copy can cause the disease. Women who have a pathogenic variant in one copy of the gene usually have less severe symptoms than males who have the disease or may have no symptoms at all. Women who have pathogenic variants in both copies of the gene would have symptoms similar to men.
A woman who carries one X-linked pathogenic variant has a 50% (1 in 2) chance of having a son or daughter who has a pathogenic variant in one copy of the gene. A man with an X-linked disease cannot pass on the disease to his sons, but all of his daughters will have a pathogenic variant in one copy of the gene. If a child is the first person in a family with the disease, the pathogenic variant may have been inherited from the mother who did not have symptoms or may have occurred by chance for the first time in the child (de novo).X-linked means the gene is located on the X chromosome, one of two sex chromosomes. Genes, like chromosomes, usually come in pairs. X-linked diseases are caused by disease-causing (pathogenic) variants in genes on the X chromosome. Mutation is an older term that is still sometimes used to mean pathogenic variant.
The inheritance pattern of many X-linked diseases is not clearly dominant or recessive and so the pattern may be stated as X-linked inheritance. Because men have only one copy of genes on the X chromosome, a pathogenic variant in one copy can cause the disease. Women who have a pathogenic variant in one copy of the gene usually have less severe symptoms than males who have the disease or may have no symptoms at all. Women who have pathogenic variants in both copies of the gene would have symptoms similar to men.
A woman who carries one X-linked pathogenic variant has a 50% (1 in 2) chance of having a son or daughter who has a pathogenic variant in one copy of the gene. A man with an X-linked disease cannot pass on the disease to his sons, but all of his daughters will have a pathogenic variant in one copy of the gene. If a child is the first person in a family with the disease, the pathogenic variant may have been inherited from the mother who did not have symptoms or may have occurred by chance for the first time in the child (de novo).
Data from Orphanet and Human Phenotype Ontology (HPO) are used to provide information on a disease's symptoms, genes, inheritance, population estimates, and more.
