Medical Genetic Conditions, Diagnostics & Treatments

Cytogenetics is the study of chromosomes, which carry genetic information (genes). The Cytogenetics Laboratory at Cedars-Sinai uses standard or specialized banding techniques or molecular cytogenetic techniques for the evaluation of both congenital (present at birth) and acquired chromosome abnormalities that have an impact on phenotype (clinical findings), reproduction and malignancy. The Cytogenetics Laboratory provides the full range of state-of-the-art services, including classical cytogenetic analysis, high-resolution chromosome analysis and molecular cytogenetics (fluorescence in situ hybridization, or FISH) on a variety of specimen types, such as blood, bone marrow, lymph nodes, solid tumors, tissue (e.g., POC or skin), amniotic fluid cells and chorionic villi or placenta.

Cytogenetic evaluation can be used to detect chromosome abnormalities responsible for birth defects and developmental problems. Chromosome abnormalities are observed in about four to eight percent of children with congenital malformations, as well as at least 13 percent of those with congenital heart defects. Chromosome abnormalities are also seen in patients with mental retardation and developmental delay, as well as a small proportion of children with autism. Some anomalies of sexual development can also be due to chromosomal abnormalities.

Cytogenetic analysis, primarily in children and young adults, is commonly done when a patient has:

• Dysmorphic appearance (minor anomalies that affect appearance)
• Mental retardation or developmental delay
• Abnormalities of sexual development
• Unexplained hypotonia
• Autism or autistic spectrum disorder, especially with mental retardation or other features
• Multiple malformations
• Pre- or postnatal growth restriction
• Short stature
• Some cardiac abnormalities (e.g. conotruncal heart defects)
• Suspected chromosomal syndrome

A significant cause of reproductive problems, cytogenetic abnormalities can be associated with a variety of issues relating to conception or giving birth. Approximately five percent of couples with recurrent miscarriage include one member with a chromosomal rearrangement. At least two percent of male infertility is associated with a chromosomal change, and 15 percent of those with azospermia can have cytogenetic abnormalities. Chromosome anomalies can be a cause of perinatal death (five percent of stillborn infants have chromosome abnormalities) and pregnancy loss (at least 60 percent of first trimester miscarriages reveal a chromosome abnormality in the fetus).

Chromosome disorders that lead to congenital abnormalities can be identified in a target population through prenatal diagnosis by amniocentesis or chorionic villi sampling (CVS). Cytogenetic analysis is commonly done for women who are pregnant or planning to become pregnant when patients have:

• Advanced maternal age
• Maternal blood screening consistent with positive screen for trisomy 21, trisomy 18 or neural tube defect (NTD) using biochemical markers (AFP, etc.)
• A fetal ultrasound that indicates abnormalities including neural tube defects, cardiac anomalies, IUGR or others
• A family history or a child with an X-linked disorder for which fetal sexing is indicated
• A child with a chromosome abnormality or a parent who carries a balanced chromosome rearrangement
• A child or fetus with multiple congenital anomalies where cytogenetic studies could not be performed
• Male infertility
• Repeated miscarriages (both male and female partners)

When cells become neoplastic, they often acquire chromosome abnormalities not seen in the normal cells of the same individual. These abnormalities can be of value in making a diagnosis, predicting prognosis and following the course of various leukemias and other cancers. The World Health Organization uses cytogenetic data as past of the criteria for classifying leukemias and lymphomas. More than 70 percent of patients with leukemia display acquired chromosome abnormalities in their leukemic cells, and between 80 and 90 percent of malignant lymph nodes will contain chromosomally abnormal cells. If the disease responds to treatment, the abnormal clone is usually lost, and only chromosomally normal cells will be detected.

Similarly, relapse or disease progression will be associated with the presence of chromosome abnormalities and increasing complexity of the abnormalities seen. Thus, cytogenetic studies can be used to monitor the course of the disease. Hematological malignancies and some solid tumors can be assessed by evaluation of appropriate cultures of peripheral blood (leukemic blood), bone marrow, lymph nodes or other tumor biopsy tissue. Standard cytogenetic analysis and FISH techniques are utilized to fully elucidate the cytogenetic diagnosis.

Common indications for cytogenetic analysis of oncology samples include:

• Chronic (unexplained) or refractory anemia
• Leukemia
• Lymphoma
• Multiple myeloma
• Neural tumors
• Pediatric leukemia, lymphoma or solid tumors
• Response to chemotherapy

For information or to request a sample pickup, call 310-423-4987.

Cedars-Sinai offers full genetic counseling services to all patients and couples at risk of genetic diseases or disorders.

Genetic counselors are healthcare providers with specialized graduate degrees and expertise in the areas of medical genetics and counseling. Trained to provide genetic counseling and risk assessment services, genetic counselors:

• Identify families at risk
• Evaluate the family for possible genetic disorders
• Analyze inheritance patterns and risks or recurrence
• Provide genetic testing information and test result interpretation
• Make referrals to other healthcare providers as needed

Individuals and families who may benefit from genetic counseling include:

• Persons or families with a history of congenital heart defects, cleft lip or palate, spina bifida, short stature or other physical birth defects
• Persons or families with genetic disorders, such as Down syndrome, cystic fibrosis, Huntington disease, muscular dystrophy, PKU, hemophilia and other inherited disorders
• Persons or families affected with mental retardation, hearing or visual impairments, learning disabilities or other conditions that could be genetic
• Persons with a history of certain cardiac, cancer, psychiatric or neurogenetic adult disorders
• Persons with a history of multiple miscarriages, stillbirths or early infant deaths involving multiple congenital anomalies
• Pregnant women at high risk due to abnormal MSAFP or ultrasound screening tests
• Women age 34 or over who are pregnant or are planning a pregnancy
• Pregnant women concerned about the effects of exposure to medication, drugs, chemicals, infectious agents, radiation or certain work conditions (This subspecialty is called teratology.)
• Persons in specific ethnic groups or geographic areas with a higher incidence of certain disorders, such as Tay-Sachs disease, breast cancer, ovarian cancer, sickle cell disease or thalassemias

Although every person carries several abnormal genes, the chance of having a child with a certain genetic abnormality is usually small. However, persons of particular racial, ethnic or geographically defined groups can have a higher than average chance of passing on genetic abnormalities that lead to specific diseases and conditions.

At Cedars-Sinai, we offer genetic screening for numerous conditions, including cystic fibrosis, Tay-Sachs disease, sickle-cell disease and thalassemia.

For adult patients who have been diagnosed with or have a family history of cancer, please contact the Genetic Screening program at the Samuel Oschin Comprehensive Cancer Institute at 800-233-2771.

For adult patients who have been diagnosed with or have a family history of heart rhythm abnormalities, cardiomyopathies or connective tissue disorders that involve the cardiovascular syndrome, please contact the Cardiogenetics Program at the Heart Institute at 310-423-2726.

If you're concerned about your child's rate of growth, we urge you to get a proper diagnosis without delay. The Growth Disorders Center at Cedars-Sinai can determine whether a problem is present, identify the causes and map out a treatment plan.

If you're concerned about your child's rate of growth, we urge you to get a proper diagnosis without delay. The Growth Disorders Center at Cedars-Sinai can determine whether a problem is present, identify the causes and map out a treatment plan.

Short stature has many causes. In general, it can be divided into two major types, proportionate and disproportionate short stature. Proportionate short stature (in which the body proportions are normal) can be due to causes such as hormonal imbalances. Once these are diagnosed they can be treated medically. Disproportionate short stature (in which the arms or legs are short relative to the body or the body is short in relation to the limbs) is usually caused by problems that affect the bones. Depending on the specific diagnosis, treatment may be available for this as well.

The Growth Disorders Center at Cedars-Sinai is an internationally renowned for providing a full range of diagnostic services, counseling for the patient and family members and treatment for certain types of growth disorders. Treatment programs include new applications of extended limb lengthening. The center also offers specialty services for related problems. These include evaluations for hormonal imbalances, vision, hearing, speech and dental problems; evaluations for neurologic symptoms (such as back pain); bone problems (such as bowlegs, clubfeet and scoliosis); and advice about family planning, obstetrical care, prenatal counseling and prenatal diagnosis.

To help each patient and family better cope with the problems associated with growth disorders, we offer professional counseling services and will assist you in obtaining any special services needed.

Cedars-Sinai's Growth Disorders Center is a national and international referral center. It also houses the International Skeletal Dysplasia Registry.

The Molecular Pathology Laboratory uses state-of-the-art equipment and the most up-to-date techniques available to diagnose and manage genetic disorders for newborns, children and adults. Intellectual disability evaluations, prenatal diagnosis and genetic counseling are also available. The lab provides consultations and molecular genetic diagnostic studies including carrier testing for autosomal recessive conditions more frequently occurring in people of Persian Jewish descent.

Clinical and laboratory services are available for the diagnosis of all forms of mental retardation and developmental disabilities. We provide patients and their families with support and advice regarding prevention and management and make referrals whenever appropriate to the California Children's Services and Regional Centers.

At Cedars-Sinai, innovative treatments are performed and research is being conducted to correct inherited ophthalmologic conditions, such as:

• Keratoconus - A type of corneal dystrophy in which the cornea gets progressively thinner. Between five and 14 percent of those who have the condition have a family history of kertoconus. It starts with the thinning of the middle of the cornea, then slowly bulges outward to form a rounded cone shape. This produces moderate to severe distortion (astigmatism) and blurriness (nearsightedness) of vision.
• Other corneal dystrophies - Disorders in which one or more parts of the cornea loses normal clarity due to a buildup of cloudy material. These diseases are usually inherited, affect both eyes equally, are not caused by outside factors (such as injury or diet), progress slowly and usually occur in otherwise healthy people. Of the more than 20 types, some of the most common corneal dystrophies include Fuchs' dystrophy, lattice dystrophy and map-dot-fingerprint dystrophy.

Treatment of Keratoconus

Keratoconus usually affects both eyes. At first, people can correct their vision with eyeglasses. But as the astigmatism worsens, they must rely on specially fitted contact lenses to improve vision. Several treatment options are available for persons with keratoconus, including:

• Rigid contact lenses, which can give high quality vision for many patients for many years with little risk.
• INTACS® prescription lenses, which are implanted in the eye
• Cornea transplants, which is the best option for patients who are contact lens intolerant. Because the cornea is avascular, this procedure is highly successful (96 to 98 percent success rate) in keratoconus.

Research into Genetic Ophthalmologic Conditions

At Cedars-Sinai, one of the world's largest clinical studies to determine genetic factors in keratoconus is currently underway. Cedars-Sinai is also participating in a clinical trial to determine the effectiveness of Excimer PRK in patients with early keratoconus. To qualify for this study, participants must:

• Be older than 40 years of age
• Have had no change in refractive error for five years,
• Have no slit-lamp signs of keratoconus
• Be contact lens intolerant
• Understand that you are at increased risk of scarring
• Understand there is no guarantee of improved vision after surgery and that a cornea transplant may be needed after surgery.

This study is being performed based on preliminary results from Europe suggesting that this may be a reasonable treatment for patients with early keratoconus. Our clinical studies suggest that it is unlikely that keratoconus will progress after age 40. There are increased risks associated with this procedure and patients who are not prepared to assume these risks should not enroll in this study.