Genetics/Metabolism

Rotation Contact

Rotation Director - Muge Calikoglu, MD

Rotation Contact - Christie Turcott, MS, CGC (christie_turcott@med.unc.edu)

First Day Information

Prior to your first day, email Christie Turcott for rotation details.

Goals and Objectives

OVERALL EDUCATIONAL GOAL:
The goal is to prepare residents for pediatric practice and/or research careers in the new age of genomic medicine. Residents should already possess an understanding of the basic principles of human genetics and then hone this knowledge by actively participating in the activities of our outpatient and inpatient consultation service. This rotation will provide residents with an opportunity to review basic principles of genetics and apply them to the diagnosis, management, and counseling of our patient population. The clinical settings include the UNC outpatient clinic, the pediatric ward, the critical care units, newborn nursery, the morgue, occasionally other medical, surgical, psychiatric inpatient units and outpatient clinics, and our satellite clinics.

OBJECTIVES:
The resident should be able to:

Elicit a comprehensive genetic family history, construct an accurate pedigree using standard
symbols , and interpret inheritance patterns of genetic disease in family histories. (PC, MK)

Perform a physical examination with attention to those findings commonly found in patients
with genetic and metabolic disease. (PC, MK)

Understand how to approach a genetic diagnostic evaluation for children with dysmorphic features, birth defects, and/or mental retardation, and recognize and classify congenital anomalies and multiple congenital anomaly syndromes. (MK)

Know the clinical features of common chromosomal aneuploidies, the signs generally associated with other kinds of chromosomal imbalance, and the indications for cytogenetic testing. (MK)

Recognize the signs and symptoms of inborn errors of metabolism and initiate the evaluation of such patients. (PC, MK)

Utilize genetic references and resources in the evaluation and management of patients. (PBL, MK, PC)

Demonstrate appropriate techniques and approaches when providing genetic counseling for commonly-encountered genetic disorders, and learning how to communicate genetic information in a manner that is suitable for each patient and family. (MK, I&CS)

Become familiar with community and educational resources for patients with genetic disorders and their families. (PBL)

Understand the importance of confidentiality and other ethical and legal issues involved in the practice of medical genetics. (PBL, MK, I&CS)

Function as a collaborator with the medical geneticist and the genetics team in evaluating, diagnosing, and managing patients with genetic disorders. (I&CS, PBL)

After the rotation, the resident should be able to:

Recognize the major signs and symptoms of children with common dysmorphological conditions;

Be familiar with complex family history taking and pedigree analysis;

Know the basic diagnostic workup and emergency management of a child with a suspected inborn error of metabolism;

Interpret normal and abnormal cytogenetic studies;

Understand when to refer patients to an academic practice and how to partner with the tertiary care center in the diagnosis and management of patients with known or suspected dysmorphic syndromes, genetic disorders and inborn errors of metabolism;

Be familiar with published references and databases available to help the physician with the diagnosis and management of patients with genetic disorders;

Be familiar with resources available for patients and families with genetic disorders.

EVALUATION:
Resident performance is evaluated by direct faculty assessment during clinical activities. An online evaluation is completed at the end
of the resident’s rotation. Residents also evaluate the faculty attending(s), and evaluate the overall effectiveness of the rotation.

LEARNING ACTIVITIES OF THE ROTATION:
The principle learning activity of the Medical Genetics rotation involves assessment of outpatients and inpatients at UNC Hospitals
and the regional satellite clinics.

Residents are expected to attend the following conferences:

the weekly pre-clinic work conference on Monday mornings
the weekly outpatient clinics on Wednesdays and Fridays
the weekly post-clinic patient conference and journal club on Thursday afternoons
the monthly molecular diagnosis lab seminars and cytogenetics seminars

Residents will attend outpatient consultations with the attendings, and perform initial evaluations on inpatient consultations before
rounding with the attending physician.

Residents are expected to read about patients ’ problems before clinics:

review medical histories
learn about diagnostic possibilities
read available references
discuss with faculty
do on-line research.

Residents are expected to utilize the genetics library of resources in the Division of Genetics offices and to learn how to access some of the on-line genetics resources such as Online Mendelian Inheritance in Man (OMIM).

Residents should read the book given to parents of new babies with Down syndrome and read literature given to parents of children with Turner syndrome and fragile X syndrome. One is expected to research the genetic aspects of a medical topic of personal interest and present at one of the weekly conferences.

Residents have the opportunity to spend one day in the Cytogenetics Laboratory to observe karyotype techniques and interpretation. They should also spend time in the Biochemical Genetics and Metabolism lab observing the interpretation of studies and application to management. Residents should contact Dr. Rao and Dr. Muenzer at the beginning of their rotations to schedule these activities.

Readings and Resources

Most residents will have less than four weeks on our service due to vacation. During that time, you likely will work with at least two attendings (one on for Dysmorphology and one on for Metabolism), one or two medical genetics fellows and our genetic counselors. There are two sections in the Division of Genetics and Metabolism: Clinical Genetics and Dysmorphology and Biochemical Genetics and Metabolism. Dysmorphology is the study of structural defects, especially congenital malformations; and metabolism is the study of disorders caused by an inherited defect in a single enzyme that results in an abnormality of metabolism. This curriculum is designed to optimize your learning during this rotation.

Required Readings:

Physical exam of the dysmorphic child: a teaching module for pediatric residents, Alice Basinger, M.D., Ph.D (4/2006) (Required)

Pre-Test

Presentation Part I

Presentation Part II

Post-Test

    Treatment of metabolic disorders, Joseph Muenzer, M.D., Ph.D. (4/2006) (Required)

    Medical genetics: 2. The diagnostic approach to the child with dysmorphic signs . Hunter AG. CMAJ. 2002 Aug 20;167(4):367-72. Review. (Required)

    Clinical genetic evaluation of the child with mental retardation or developmental delays. Moeshler JB et al. Pediatrics. 2006 Jun;117(6):2304-16. (required)

    Emergency management of inherited metabolic diseases. Prietsch V et al. J Inherit Metab Dis. 2002 Nov;25(7):531-46. (Required)

    Clinical genetics evaluation in identifying the etiology of autism spectrum disorders. Schaefer GB, Mendelsohn NJ et al. Genet Med. 2008 Apr;10(4):301-5. (Required)

    Use of array-based technology in the practice of medical genetics. Manning M, Hudgins L. Genet Med. 2007 Sep;9(9):650-3. (Required)

    Indications for genetic referral: a guide for healthcare providers. Pletcher BA, Toriello HV, et al. Genet Med. 2007 Jun;9(6):385-9. (Required)

    Suggested readings:

    Genetic Aspects of Development and Birth Defects, Cynthia M. Powell, MD (4/2006)

    Pediatric neurogenetics, Zheng (Jane) Fan, MD (6/2006)

    Newborn Screening 1958-2006, Dianne Frazier PhD, MPH (4/2006)

    Diagnostic evaluation of developmental delay/mental retardation: An overview. Battaglia A, Carey JC. Am J Med Genet C Semin Med Genet. 2003 Feb 15;117C(1):3-14. Review.

    Specific genetic disorders and autism: clinical contribution towards their identification. Cohen D, , Pichard N, et al. Autism Dev Disord. 2005 Feb;35(1):103-16. Review.

    Molecular genetics of Marfan syndrome. Boileau C, Jondeau G, et al. Curr Opin Cardiol. 2005 May;20(3):194-200. Review.

    Chromosome map, Gene and diseases, NIH electronic books.

    Evaluation of mental retardation: recommendations of a Consensus Conference: American College of Medical Genetics. Curry CJ, Stevenson RE, et al. Am J Med Genet. 1997 Nov 12;72(4):468-77. Review.

    Current strategies for the management of neonatal urea cycle disorders. Sumnar M, Tuchman M. J Pediatr. 2001 Jan;138(1 Suppl):S6-10.

    Inborn errors of metabolism in infancy: a guide to diagnosis. Burton BK. Pediatrics. 1998 Dec;102(6):E69. Review.

    Mitochondrial disorders. Zeviani M, DiDonato S. Brain. 2004 Oct;127(Pt 10):2153-72. Review.

    Biochemical findings in common inborn errors of metabolism . Pasquali M, Monsen G, et al. Am J Med Genet C Semin Med Genet. 2006 May 15;142C(2):64-76.

    Websites:

      http://geneclinics.org

        This is a great source of reviews for many metabolic disorders, dysmorphology syndromes, and cancers. It is frequently updated by experts in each field. Also, there is a great section for specialty labs, so you can figure out where to send your tests.

          OMIM (online mendelian inheritance in man)

            This is part of the collection that includes PubMed. The address is long, so I just Google OMIM and get there. It is a compendium of short reviews of papers published about many genetic and metabolic disorders. It is a good place to look with the patient’s symptoms to help generate a differential diagnosis. The clinical synopsis on the side bar is helpful, too.

              Genetics Home Reference: ghr.nlm.nih.gov

                Good website for basics of human genetics, common genetic disorders, and also good for handouts.

                  University of Washington neuromuscular disease: neuromuscular.wustl.edu

                    It has extensive information about neuromuscular disease, including updated genetic information.

                      eMedicine: www.emedicine.com

                        National Newborn Screening and Genetics Resources Center: genes-r-us.uthscsa.edu

                          National database about newborn screening, with a state-by-state guide to what is covered in the test and whom you may contact in your areas with metabolic genetics questions.

                            Newborn Screening Act Sheets and Confirmatory Algorithms

                              This excellent resource is for physicians and others who manage abnormal newborn screening results. The goal is to provide some standardized guidance, and this set is sponsored by the American College of Medical Genetics (and just released this month). Good action (ACT) sheet for immediate intervention and good algorithm to help you know what to do. You probably won’t use this…until you get a call about an abnormal NBS result. The abnormal results usually get to the primary care doctor on Friday afternoon.

                                Screening, Technology and Research in Genetics: newbornscreening.info

                                  Good patient and practitioner handouts. Set up by several western states for all to use.

                                  Interactive Neuroimagning

                                  Reference books:

                                    Thompson and Thompson Genetics in Medicine (loaner copy is available), Saunders, 5th ed, 1991.

                                    Nelson’s Pediatrics (good diagrams of metabolic pathways)

                                    The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID)

                                    Smith's Recognizable Patterns of Human Malformation (6th ed) by Jones, Saunders, 2005.

                                    Syndromes of the Head and Neck, Gorlin et al. 4th ed, Oxford, 2001.

                                    Management of Genetic Syndromes, Cassidy and Allanson, Wiley-Liss, 2nd ed, 2004.

                                    Glossary:

                                      Glossary of genetic terms

                                        Glossary of malformations