Chapter 11: Genetic Counseling

Introduction Genetic counseling has been practiced for thousands of years. For example, the Babylonian Talmud (completed in the 7th century AD) clearly states that a mother is to refrain from circumcising her son if two previous sons had died from (uncontrollable bleeding caused by) a circumcision. Today, the enormous expansion of molecular knowledge makes genetic […]

Chapter 12: The Diagnostic Approach for a Child with Multiple Anomalies or Dysmorphic Features

Introduction A clinical geneticist is often one of the first of several specialists called to evaluate a newborn with multiple congenital anomalies with or without dysmorphic features. Likewise, when two or more systems are involved in the medical history of an individual, the expertise of a clinical geneticist is often sought to help the team […]

Chapter 13: Malformations and Other Morphological Disturbances

Introduction Abnormal anatomic development is the result of one or more pathogenically distinct processes, each resulting from a different mechanism and categorized by the genetic and embryologic bases of the disturbance. Important distinctions include: Whether a morphological disturbance is caused endogenously (genetically) or exogenously Whether it is an isolated occurrence or an occurrence in combination […]

Chapter 14: Risk Estimation and Calculation

Introduction Consider the following three classic counseling situations that can occur in clinical human genetics: A person seeking clinical advice is aware of a congenital disorder in the family and wishes to know the likelihood that he or she will be affected. A person seeking advice knows that he or she is a carrier for […]

Chapter 15: Methods for Laboratory Diagnostics in Genetics

Cytogenetics The term cytogenetics refers to the study of chromosomes, their structure, and their inheritance mechanisms. In 1956, Tijo and Levan discovered that a human somatic cell had 46 chromosomes (Fig. 15.1), and since then cytogenetics has been the reference point for subsequent genomic discoveries and the premiere diagnostic test for patients with various genetic […]

Chapter 16: Metabolic Diagnostics and Newborn Screening

Introduction Inborn errors of metabolism constitute a broad group of disorders that are characterized by the inability of the body to convert or break down one substance (substrate) to another (product). These disorders are typically due to the absence or insufficiency of crucial enzymes or cofactors and are usually inherited in an autosomal recessive or […]

Chapter 17: Prenatal Genetic Evaluation

Introduction Prenatal testing for genetic conditions began in 1966 when Mark W. Steele and W. Roy Bregg demonstrated that the chromosomal constitution of a fetus could be examined with cultured amniotic fluid cells. Prenatal diagnostics is now a major medical subspecialty that relies on the expertise of obstetricians, clinical geneticists, and genetic counselors to deliver […]

Chapter 18: Ethical Concerns in Medical Genetics

Introduction Over the past century there have been tremendous discoveries in medical genetics and molecular biology. Since the double helical structure of DNA was elucidated in 1953 and the genetic code deciphered, these disciplines have grown exponentially. The resulting advancements have had very practical applications in the treatment of disease, the determination of disease risk, […]

Chapter 19: Multiple Congenital Anomalies

Introduction Newborns with multiple congenital anomalies (MCAs) or malformations represent a common cause for genetics consultation. Please refer to Sections 13.2 and 13.3 for important definitions, including malformation, deformation, and disruption. Important Multiple congenital anomalies are defined as either:   Two or more major malformations (e.g., neural tube defects, congenital heart defects, and anal atresia) Three […]

Chapter 20: Skin and Connective Tissue

Introduction As the largest human organ, the skin is critically important in every clinical genetic examination. Skin changes can provide valuable evidence for numerous genetic diseases. Of special importance is the pigmentation of the skin (hyperpigmentation or hypopigmentation); also important are its texture and elasticity. The distribution of skin changes can indicate when, during embryonic […]