Information For Patients

Appointments for a genetic evaluation can be scheduled by calling (203)785-2660. Your healthcare provider must make a referral for genetics evaluation via the EPIC electronic medical record, and our schedulers will contact you to schedule an appointment.

You or your child has been referred for a genetics evaluation because your medical condition or a condition affecting a family member has, or is suspected to have, an underlying genetic basis. Identifying the underlying genetic cause of your or your child’s medical condition may have substantial health benefits. It will provide information about prognosis and guidance for managing the condition and help you and your doctors make informed decisions about your health care. It may influence treatment options either currently or in the future. Establishing the genetic basis of a disorder will allow for accurate genetic counseling about the risk of occurrence of the disorder in other relatives, family planning, and reproductive options. An evaluation by a medical geneticist will determine what, if any, genetic testing is appropriate for you or your child.

Before your appointment, gather as much information as possible about any health problems present in your relatives, including children, brothers and sisters, aunts and uncles, grandparents, and cousins. For deceased relatives, obtain information about age and cause of death.

In addition, please bring any pertinent medical records not in the Yale New Haven Hospital (YNHH) electronic medical record system to your appointment.

Each evaluation is different and is tailored to the specific reason why you or your child has been referred. If laboratory testing is recommended, more than one visit may be necessary to provide a complete assessment of your situation. Below is typically what to expect from a genetics evaluation:

1. Collection of family history, review of medical history, and any prior testing that has been performed. Some of this information may be collected before your visit.
2. Physical examination by a clinical geneticist.
   
3. Assessment: Based on the results of the physical examination, family history, review of medical records, laboratory testing, and other relevant findings, the clinical geneticist will decide whether any testing is recommended. Genetic testing may be proposed to look for an underlying genetic explanation.
4. Genetic testing (a simple blood draw) and/or a referral to another specialist, if appropriate for your situation.
   
   The genomic testing that your healthcare provider has ordered is for clinical purposes and is not a research study. Consent is not required for clinical testing, but your healthcare provider may wish you to read and sign the attached form indicating that you received the information.
5. Assessment and genetic counseling: We will provide conclusions based on all the information we have gathered about you or your child. Our discussion will usually include our interpretation of the results of any genetic testing that has been performed, what is known about the disorder, the recommendations for management of the disorder, the inheritance pattern, and the implications for other family members. Genetic counseling may occur at the initial genetic evaluation or in subsequent visits once the genetic testing results are available.

Our team of medical geneticists and genetic counselors will meet with you to interpret test results and what they mean for you, your child, and other family members. Depending on your or your child’s specific diagnosis, our medical geneticists, genetic counselors, APRNs, and nutritionists will continue to provide medical care and/or refer you to appropriate medical specialists if necessary. We frequently collaborate with pediatric and adult specialists in cardiology, neurology, obstetrics, gynecology, surgery, dermatology, nephrology, orthopedics, ophthalmology, and oncology. We also closely collaborate with multidisciplinary clinics in dermatology, cardiology, neurology, endocrinology, orthopedics, ENT, urology, gynecology, and maternal-fetal medicine, as well as with those in the Yale Fertility Center and the Smilow Cancer Genetics and Prevention Program.

The approach to genetic testing is individualized and based on the patient’s medical and family history.

The results of genetic testing are placed in the electronic medical record, which you can access using MyChart. Physicians caring for you who have access to the YNHH electronic medical record will also have access to your results. Your results can also be faxed to providers who are not in the YNHH network.

We will take all reasonable measures to maintain the confidentiality of your personal health information, which may be shared with others for public health reporting and legal compliance as required.

We strongly encourage you to share your or your child’s genetic testing results with other relatives when the results indicate that other family members are at significant risk for having or developing a genetic disorder. Being forewarned about the increased risk of an inherited disorder can help relatives seek appropriate medical care, which can have significant health benefits in some circumstances. We recognize that some individuals may be reluctant to share information with other family members, and the decision to do so is personal. Our team of genetic counselors and medical geneticists can assist in this process by providing suggestions about the best approach to informing other family members and written informational materials that you can share. Our team is happy to speak to your relatives but would only do so with your written consent. Your test results will not be disclosed to anyone in your family without your permission.

Several types of genetic testing are available, including DNA testing (known as molecular analysis), chromosome testing, chromosome microarray, and biochemical testing. The type of genetic testing that may be recommended will vary depending on the reason for the genetics evaluation and from patient to patient.

Learn more about genetic testing at the Centers for Disease Control & Prevention (CDC) - Genetic testing

DNA is a molecule inside our cells that contains the genetic information (genes) that provide instructions for the development and normal function of the cells and structures of our body. DNA is built from a specific combination (sequence) of four smaller molecules called nucleotides, the genetic blueprint for our development. Genetic disorders result from abnormal changes in the sequence of these nucleotides, which affect normal development and function. Those changes can be inherited from one or both parents or occur for the first time in an egg or sperm. Humans have about 20,000 pairs of genes. We inherit one of each pair from our mother and one from our father.

DNA testing involves examining DNA extracted from a person’s blood cells or other body tissues such as saliva. A DNA test examines the sequence of the nucleotides in one or many genes to identify abnormal changes that can be associated with a person’s symptoms. It's like finding a typo or error in the sequence of one of those genes, which could explain why someone has a specific health problem.

DNA tests can be limited or large in scope, depending on the reason for the genetics evaluation. For some people, testing may be restricted to the DNA sequence analysis of only a single gene (known as single gene testing). For others, analyzing the DNA sequence of more than one gene (panel testing) or the sequence of all a person’s DNA (whole exome or whole genome sequencing) may be recommended. The scope of ordered DNA testing depends on your or your child’s medical condition. More about those tests is explained below.

The genomic testing that your healthcare provider has ordered is for clinical purposes and is not a research study. Consent is not required for clinical testing, but your healthcare provider may wish you to sign a form indicating that you received the information about the testing process.

Learn more about molecular diagnosis

Whole exome sequencing (extended gene analysis) involves analysis of the DNA sequence contained in the exons of all our genes. Exons are the part of our genes that code for proteins. Proteins are complex molecules in our cells required for normal development and maintenance of normal function of the body’s tissues and organs. The exons comprise only 1-2% of our DNA but play the most significant role in our health and development. All of a person’s exons together are called the exome, instead of analyzing all of our DNA. WES involves only analyzing 1-2% (the exome) of our DNA. Whole exome sequencing is typically used when it is unclear what specific genes might be causing a person’s symptoms.

Learn more about Whole Exome Sequencing (WES)

Limited panel testing looks for abnormal changes (variants) in the exons of more than one gene. Limited panel testing is used when changes in a specific group of genes could explain a person’s symptoms. The number of genes in a limited panel includes those known to cause symptoms consistent with the patient’s symptoms and can range from two to many hundred genes. For example, hearing loss can be caused by an abnormal variant in one of a few hundred genes.

A single gene test is a molecular DNA-based test that searches for variants in the exons of a specific gene. Testing of a single gene (instead of analysis of many different genes) is used when a person has symptoms that strongly suggest a specific genetic disorder and where the symptoms of that disorder only occur due to abnormal DNA changes (variants) in one specific gene.

Single gene analysis, gene panel testing, and whole exome sequencing involve analysis of the exons, which are the protein-coding portions of our genes. About 85% of abnormal changes in the DNA sequence that cause genetic conditions are present in the exome. The remainder is not located in the exome and thus is undetectable by these testing methods. In addition, some abnormal gene changes in the exome may not be detectable by current sequencing technology.

This method analyzes the entire DNA sequence, including all the exons and non-protein coding portions of our genes). This test provides the most information about a person’s DNA sequence. Its use is restricted to cases where a genetic disorder is strongly suspected, but whole exome sequencing has not identified an underlying cause.

Learn more about Whole Genome Sequencing (WGS)

No variant is identified [negative (normal) report]: No genetic change (variant) was found to explain the patient's medical condition. This result reduces but does not eliminate the possibility that the medical condition has a genetic basis. It is still possible that an abnormal change in the DNA sequence is present but cannot be detected by current testing methods. Additional testing using other testing methods or future re-analysis of the data from the current test may be recommended. Interpretation of a normal result depends on your specific situation.

A pathogenic variant is identified [positive (abnormal) report]: One or more abnormal gene variants are identified causing the patient's medical condition or predict the patient has an increased risk of developing a medical condition. This type of genetic test result can be used to diagnose and make decisions about patient care, including treatment and surveillance.

A likely pathogenic variant is identified [a qualified positive (abnormal) report]: The genetic test result gives sufficient evidence to justify using it in clinical decision-making combined with other evidence for the disease to make the best decision about the patient’s medical care (e.g., X-ray studies or other laboratory tests).

A variant of uncertain significance: A DNA sequence change was identified. However, there is insufficient information to determine whether it is disease-causing or represents normal human variation. Changes in the DNA sequence (variants) are common in all our genes. A substantial proportion of uncertain significance variants prove normal as more data becomes available. Variants of uncertain significance should not be used in clinical decision-making. Sometimes, testing other family members can provide more information about the clinical importance of a variant of uncertain significance.

Incidental findings: Because many genes are examined in genetic panel testing, this analysis may uncover a different genetic disorder unrelated to the medical condition being tested. This is known as an incidental finding. Genetic disorders that can be treated ("actionable incidental findings") are reported, following the standards of care recommended by medical societies. Incidental findings often relate to treatable heart or treatable conditions that might increase cancer risk. Incidental genetic findings are less common than incidental findings in many other routine medical tests, such as CT scans and MRIs. Depending on the type of genetic testing you or your child is having, we will discuss with you the option of receiving incidental findings.

Chromosomes are the structures inside cells that contain our DNA. A chromosomal test analyzes whole and large pieces of chromosomes to determine whether there are significant genetic changes, such as an extra copy of a chromosome or a large missing or extra piece of chromosome, that can cause a genetic condition. A chromosome test is usually performed on blood cells; it can also be performed on cells obtained from other tissues in the body, including amniotic fluid cells, cells from the placenta, and saliva.

This technology can find missing or extra pieces of genetic material on the chromosomes that are too small to be detected by the basic chromosome test but could cause a genetic disorder. A chromosome microarray can be performed on DNA obtained from blood cells and on DNA from cells obtained from other tissues in the body, such as saliva.

A protein or enzyme test is a biochemical test that studies the amount or activity level of the product of a gene rather than the gene itself. Abnormalities in the amount or activity of an enzyme can indicate an underlying genetic disorder. A protein or enzyme test can usually be performed using blood cells. Occasionally, skin cells might be required.

Disorders with autosomal recessive inheritance are caused by an abnormal change (pathogenic variant) in both copies of the same gene, one inherited from the mother and one from the father. For couples whose parents are carriers of one copy of the pathogenic variant, the risk of an affected child in each pregnancy is 25% (1 in 4). The risk is the same in each pregnancy, regardless of whether a previous child is affected and irrespective of the sex of the child.

Individuals who are carriers of only one copy of the pathogenic variant for an autosomal recessive disorder also have a normal copy of the gene and typically do not have significant or any health problems associated with the disorder.

Autosomal dominant means that having only one abnormal copy (pathogenic variant) of the gene is sufficient to result in the manifestation of the disorder. The variant can come from an affected mother or father (inherited) or arise as a new change in an egg or sperm (de novo).

Each child of a parent affected by an autosomal dominant disorder has a 50% chance of inheriting the pathogenic variant. This risk is the same for each child and is regardless of the sex of the child or the affected parent. If a child does not inherit the parent’s pathogenic variant, the child will not be affected by the disorder, nor can that child transmit the pathogenic variant to future generations.

A disorder with X-linked inheritance is caused by an abnormal gene change (pathogenic variant) on the X chromosome. Males have one X chromosome (always inherited from their mother) and one Y chromosome (always inherited from their father). Females have two X chromosomes (one inherited from each parent).

A male with a pathogenic variant for an X-linked disorder will typically be affected.

Females who carry a pathogenic variant on one of their X chromosomes are typically unaffected or have milder symptoms of the disorder. This is because females also have a normal gene copy on their other X chromosome.

Each son of a female carrier of an X-linked disorder has a 50% chance of inheriting the pathogenic variant and being affected by the disorder. Each daughter of a female carrier will have a 50% chance of inheriting the pathogenic variant herself and be at risk of having affected sons.

Males affected by an X-linked recessive disorder transmit their X chromosome with the pathogenic variant to all their daughters but not their sons. Each daughter would be a carrier and have a 50% risk of having an affected son in each pregnancy.

What is DNA?

DNA is the molecule inside almost all our cells that is the genetic blueprint for our development. It provides instructions for the function of our body’s cells, organs, and other structures. DNA is a very large molecule built from a specific combination (sequence) of four smaller molecules called nucleotides. Genetic disorders result from abnormal changes in the sequence of these nucleotides, which can affect normal development and function.

What is a gene?

A gene is a specific segment of DNA containing a specific sequence of nucleotides. A gene codes for forming one or more specific proteins that have specific functions in some or all body cells. Each gene contains hundreds to thousands of nucleotides strung together in a particular sequence.

Humans have about 20,000 pairs of genes that code for thousands of different proteins. We inherit one of each pair of genes from our mother and one from our father.

What are proteins?

Proteins are large complex molecules that carry out a vast array of essential functions in our body. For example, these functions include enzyme reactions, transmitting chemical signals between cells and throughout the body, maintaining structure and support for cells and body structures, and creating antibodies to prevent infection. The sequence of DNA determines the structure of a protein.

What are exons?

Exons are the regions of genes that code for proteins.

What are introns?

Introns are the regions of genes that do not code for proteins.

What is an exome?

An exome is the sequence of all the genes' exons in an individual’s genome. In humans, the exome is about 1.5% of the entire genome. Most disease-causing changes in the gene sequence occur in the exome. A study of the exome is known as extended gene analysis.

What is a genome?

A genome is an individual's DNA sequence and includes exons and introns.

What is a pathogenic or likely pathogenic variant in a gene?

A pathogenic variant is a change in the gene sequence that can result in a genetic disorder or an increased risk of having that disorder.

What is a variant of uncertain significance in a gene?

A variant of uncertain significance is a change in the gene sequence for which there is insufficient information to determine whether it is disease-causing or represents normal human variation. Changes in the DNA sequence (variants) are common in all our genes. A substantial proportion of uncertain significance variants prove normal as more data becomes available. Variants of uncertain significance should not be used in clinical decision-making. Sometimes, testing other family members can provide more information about the clinical importance of a variant of uncertain significance.

What is a benign variant?

A benign variant is a DNA sequence change with no health consequences. Benign variants reflect normal human variation in the DNA sequence.

What is a chromosome?

A chromosome is a long, thread-like structure found in the nucleus of our cells. Our DNA is packaged into chromosomes. Humans have 23 pairs of chromosomes. Females have two X chromosomes, and males have one X and one Y chromosome. We inherit one of each pair from our mother and one from our father.

Below are some of the most common resources that can direct families to other patients with the same or similar conditions/disorders/syndromes/diseases. Consider also other media platforms like Facebook.

• U.S. Dpt. of Health and Human Services. National Institutes of Health. Rare Diseases Community
• National Organization for Rare Disorders | NORD
• Rare Disease Community and Support
• Science & Innovation - uniQure
• Broad Institute. Patients with rare diseases meet their matches
• Health Resources & Services Administration. Newborn screening
• Centers for Disease Control and Prevention. Newborn Screening Portal
• National Cancer Institute
• Force. Facing Hereditary Cancer EMPOWERED
• Genetic and Rare Diseases Information Center
• EveryLife Foundation
• Global Genes
• Lysosomal Disease Network