Handbook of Genetic Counseling/Balanced Robertsonian Translocation

Balanced Robertsonian Translocation

Contracting

 * Why were you referred here today?
 * What are you most concerned about?
 * Outline goals of session namely talking about causes of developmental delay, explaining the results of lab test - balanced robertsonian translocation, and examination

Elicit Medical History

 * Ask about history of delays and developmental milestones.
 * Ask about any perinatal infections.
 * Ask after past and current interventions.
 * Get pregnancy history of the mother including any infections or exposures to possible teratogens.
 * Ask about history of miscarriages or stillbirths.

Family History

 * Ask specifically about occurrence of miscarriage or stillbirth on mother and father's side of family.
 * Also ask about history of delays in family members and mental retardation.

Genes and Chromosomes

 * Use Greenwood book and karyotype in explanation.
 * Cells make up the body; each cell contains chromosomes which are made of a chemical called DNA which in turn contains genes.
 * Genes are like recipes that are instructions to make proteins such as skin, muscle and organs.
 * In the lab, technicians break open the cell and these are what chromosomes look like.
 * There are 46 chromosomes total in humans, 23 come from mom in her egg and 23 from dad in his sperm. So one chromosome 1 comes from mom and the other from dad to form the 23 pairs.
 * The 23rd pair are called the sex chromosomes. Women have two XXs and Men have an X and Y. The Y chromosomes is not really shaped like a Y, but is named that to distinguish it from the X.
 * Chromosomes are able to exchange DNA with each other. Sometimes this happens with two different chromosomes of different pairs such as number 13 and 15. Also, an arm of one chromosome can become attached to the arm of another. These are called translocations.
 * Certain chromosomes with one very short arm and one very long arm are involved in a Robertsonian translocation. The short arms become detached from the long arms and are lost, but the long arms attach to each other forming one large chromosome from two smaller ones. The small arms of these chromosomes do not contain genes, so no significant information is lost. This is called a balanced Robertsonian translocation.
 * Your lab results show that this happened between one chromosome 13 and a one 15. Because the two chromosomes essentially joined together into one, the lab report shows you have 45 chromosomes instead of 46.

Robertsonian Translocations

 * Can occur de novo or can be inherited.
 * Cytogenetic testing of blood relatives can be done to detect de novo or familial translocation.
 * Are one of most common types of translocation and is detected in 1/1000 fetuses by amniocentesis.
 * Occurs in a germ cell before meiosis and involves the acrocentric chromosomes 13, 14, 15 (D), and 21, 22 (G).
 * The short arms of two chromosomes are lost and the long arms joined end to end at the centromeres. They may be homologous or non-homologous chromosomes that are joined, e.g. t21;21 or t13;15 respectively.
 * D/D translocations occur between chr. 13-15. D/G occurs between one of 13-15 and one 21-22. G/G occurs between 21-22.

Balanced and Unbalanced Translocations

 * Balanced translocations normally do not cause any abnormal phenotype.
 * Unbalanced translocations can cause miscarriage, stillbirth, or a birth of a baby with multiple malformations, developmental delay, and mental retardation (Maternal-Fetal Medicine: Principles and Practices, 1994).
 * Unbalanced translocations occur when a diploid germ cell with a translocation goes through meiosis. Abnormal segregation of the chromosomes in which only a portion or more than 1 copy of any part of either chromosome involved in the translocation can result in a fetus with an unbalanced translocation upon fertilization.

Risks Associated with Balanced Translocation Carriers

 * If a familial translocation has been detected through an individual with an unbalanced translocation, then the recurrence risk of having another child with an unbalanced translocation is 15%.
 * If not biased by the presence of an individual with an unbalanced translocation, then the recurrence risk is 1-2%.
 * Risk for both situations for spontaneous miscarriage is 25%.
 * Couples with a D/D translocation are at decreased risk (1-2%) of having a child with an unbalanced translocation since loss or gain of genetic information in these chromosomes is lethal.
 * Maternal carriers of balanced translocations have greater likelihood than paternal carriers of having children with unbalanced translocations.

Developmental Delay

 * Unknown cause in 50% of cases.
 * Result of environmental and/or genetic factors.
 * Approximately 2000 genetic causes are known which include chromosomal abnormalities, metabolic or endocrine disorders, hereditary degenerative disorders, hormonal deficiency, hereditary syndromes.
 * Environmental causes are infection, irradiation, or exposure to certain toxins during prenatal development. Peri or postnatal causes are prematurity, anoxia, cerebral damage, infection, toxins, hormone deficiencies, metabolic disorders, epilepsy.
 * Prevalence of people with some form of mental retardation is 1-3% in US.
 * Intervention services are available very early and reach into adulthood. Assessment of development done at CCDD. School system provides services in the form of Individualized Education Plan (IEP) and focuses on special services like speech therapy. Adults can be provided with job training and many live in group homes.

Clinical Features of Mental Retardation

 * Affects developmental and cognitive abilities.
 * IQ score lower than 70.
 * Ranges are: Mild, 50-55 to 70; Moderate, 35-40 to 50-55; Severe, 20-25 to 35-40; Profound, below 20-25.
 * Most individuals with MR range between 55-69.
 * People with MR may have limits in the following: communication, work, self-care, social skills, self-direction, and academic skills, living alone.
 * Onset is before 18 years.

Recurrence Risks

 * Difficult to calculate risk if cause is unknown.
 * Empiric risk around 10%

Psychosocial Issues

 * Provision of adequate intervention
 * Burden of taking care of individual with MR
 * Affects sibling and other family relationships.
 * Uncertainty as to cause of MR and recurrence risks.