Introduction to Medical Genetics - PowerPoint

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					Introduction to Medical Genetics
        Unit 8 - 2007
     David S. Rosenblatt, M.D.
           Medical Genetics
            Practice Profile
•   Syndromology
•   Inherited Metabolic Disease
•   Prenatal Diagnosis
•   Cancer Genetics
•   Neurogenetics
•   Psychiatric Genetics
•   Cytogenetic, Molecular Genetic, and
    Biochemical Genetics laboratory services
Medical Genetics-Syndromology
 • Children and adults with dysmorphic
   features (physical findings that alter
 • Children and adults with syndromes
   (conditions with physical and/or laboratory
   findings that occur together in
   recognizable patterns)
 • Diagnosis and genetics counselling.
   Important for prognosis and reproductive
   counselling and also treatment.
           Pediatric Genetics

• Birth defects (CHD, NTD,
  CL/CP) or multiple
• Dysmorphic features
• Metabolic disease
• Chromosomal abnormalities
• Mental retardation, devel.
  delay                        Children’s Hospital Boston
            Pediatric Genetics

• Ambiguous genitalia,
  abnormal sexual
• Unexplained hearing/visual
• Abnormal stature (short, tall,
  disproportionate) or growth
  pattern (asymmetric)
                                   Children’s Hospital Boston
• Consanguinity
         Medical Genetics
    Inherited Metabolic Disease
•   Newborn Sreening (e.g. PKU)
•   Neonatal onset
•   Sudden infant death (e.g. MCAD)
•   Childhood onset
•   Adolescent onset
•   Adult onset
•   Opportunities for prevention, diagnosis
    and management
         Medical Genetics
        Prenatal Diagnosis
• Screening: Maternal serum, ultrasound
• Diagnosis: ultrasound, MRI,
  aminocentesis, chorionic villus biopsy,
  biochemical analysis, molecular analysis
• Treatment: Early delivery, fetal surgery
• Genetic counselling: Options for
  pregnancy and recurrent risks.
          Prenatal Diagnosis

Indications for referral:
Increased risk chromosome
  – Advanced maternal age
  – Abnormal (positive) results of screening
  – Previous child with a chromosome
            Prenatal Diagnosis

Indications for Referral:
• Teratogen exposure
• Family history of other genetic disorder or
• Infertility

                                         American Fertility
   Abnormal findings on ultrasound

                                           San Jose Obstetrix Medical Group

Memorial Health System, Colorado Springs
Genetic Counselling in Prenatal
• Information giving
• Psychological counselling
  – Decisions
  – TOP often late (DMD)
• Follow up care
  – Referrals

                           Ob/Gyn Specialists of the Palm Beaches
          Medical Genetics
          Cancer Genetics
•   Breast Cancer (BRCA)
•   Colon Cancer (FAP and HNPCC)
•   Cancer Syndromes (many)
•   Prevention, diagnosis, treatment
•   Genetic counselling and testing
                     Cancer Genetics
Clues to cancer syndromes:
•   Multiple family members
•   Bilateral
•   Early onset
•   Multiple primaries
•   Rare cancers

Content courtesy Robin M. Troxell, MS   Seattle Cancer Care Alliance
             Cancer Genetics

Breast and

                  Penrose Cancer Center (Centura Health)
         Medical Genetics
• Developmental delay (mental retardation)
• Epilepsy
• Syndromes (many neurological)
• Metabolic (many metabolic disease:
  particular involvement with mitochondrial
  and neuromuscular disease)
• Movement disorders (Hereditary ataxias)
            Adult Genetics

• Adult-onset conditions
    AD Alzheimer’s
    Psychiatric disease

          Medical Genetics
         Psychiatric Genetics
•   Schizophrenia
•   Bipolar disease
•   Alcoholism
•   Autism

• Limited clinical application at present
            Adult Genetics

Myriad other indications
• Bleeding disorders
• Unusual dermatological findings
• Sudden cardiac death
• Connective tissue disorders
Marfan Syndrome

    Slide courtesy Lance Grau, MS
       Medical Genetics
       Clinical Laboratory
• Cytogenetics
• Biochemical Genetics
• Molecular Genetics
Medical Genetics & Family Medicine
      Today and Tomorrow
• Family History (online resources for
• Be alert-first contact with patient and
• Be aware of resources
• Predisposition to common disease (heart
  disease, asthma)
Follow families and ensure continuity of care
Medical Genetics & Specialty Medicine
        Today and Tomorrow
 • Family history
 • Expertise in specific areas of genetic
 • Opportunities for fellowships in clinical or
   clinical laboratory genetics
 • New therapies (gene therapy, stem cells)
 • Common disease (Role of Genomics)
    Cautions and Challenges

• Be aware of GenoHYPE (Not everything is
  ready for “prime time”
• Avoid cynicism (Advances have already
  and will in the future lead to better care)
• Use resources (OMIM, PubMed, Genetest,
  Geneclinics etc)
• Genetics and genomics will be part of your
  practice no matter what you choose
Department of Human Genetics:
       Clinical Training
Royal College of Physicians and Surgeons
  of Canada
• College of Physicians of Quebec
• Canadian College of Medical Geneticists
(also certifies PhD Medical Geneticists –
  primarily as laboratory director)
            CCMG Training
• Entry after M.D. and core training or after
  Ph.D. in Genetics.
• Most candidates train for 2 years to
  become laboratory directors in either
  cytogenetics, biochemical genetics, or
  molecular genetics.
• Rarely, Ph.D. trains for 2 years as clinical
  RCPSC and CMQ Training in
      Medical Genetics
• Medical Genetics is a Primary Specialty-
  entry is directly from medical school.
• Residency is for a period of 5 years with
  the first two core years in pediatrics,
  medicine and high risk obstetrics.
• Exposure to biochemical, cytogenetic and
  molecular genetic laboratories in year 3.
• Exposure to all other aspects of Medical
  Genetics in years 3, 4 and 5.
                                              A communication
                                              process dealing with
                                              the human problems
                                              associated with the
                                              occurrence, or the risk
                                              of occurrence, of a
                                              genetic disorder in a
                                               Am J Hum Genet 1975: 27:240-242

University of Arkansas for Medical Sciences

Help the individual or family to:
• Comprehend the medical facts (dx, course,
• Appreciate the role of heredity and individual
• Understand the alternatives for dealing with risks

                        American Society of Human Genetics, 1975

Help the individual or family to:
• Choose a course of action in accordance with
  their risk, family goals, and ethical and religious
• Make the best possible adjustment to the

                         American Society of Human Genetics, 1975
Counselling Contexts and
 • Prenatal and preconceptional
 • Pediatrics
 • Adult - incl. familial cancers
The genetic counselling
 What goes on in a genetics
 The Medical Genetics Evaluation

1. “Contracting” – why there?
1. History Taking
       sometimes by questionnaire
2.   Physical exam
3.   Risk assessment
                           Roles of the geneticist &
4.   Diagnostic studies    GC overlap – shift & flow
5.   Counselling           according to case
6.   Follow up             Physician more medical,
                           GC more psychosocial
        Genetic counsellors:

• Strive to be nondirective, culturally
• Consider the family as patient, eg
  translocation carriers
• Pay extra attention to psychosocial
  dimensions – support, eg pregnant
  patient with CF
• Testing may -> insurance, employment
• Costs (BRCA sequencing ~US $4,000)
• Inconclusive or negative results
• Testing of minors – parents want;
  ethicists don’t
• Nonpaternity
• Other ethical issues – rights of the
• Field evolving rapidly
  – Duty to recontact?
  – Diagnoses can be changed (SLO -> unknown)
• Process is time consuming
  – Must introduce many new concepts
  – Decision making in crisis
• Lack of primary care providers
• Needs of the population