Course Medical genetics is a mandatory course based on clinical reasoning in the fifth year of the University integrated undergraduate and graduate study of Medicine in English, and consists of 18 hours of lectures, 14 hours of seminars and 13 hourse of practicals, with a total of 45 hours (3 ECTS). The aim of the course is to describe and explain the comprehensive approach to a patient with a genetic disease or disorder or an increased risk for them, so that future physicians can apply the acquired knowledge, skills and attitudes in their own clinical practice.
COURSE LEARNING OUTCOMES:
Learning outcomes are determined and derived in accordance with the basic standards for the development of genetics competencies for health professionals in Europe, specifically physicians who are not specialists in medical genetics. These competencies are contained in the document Core competencies in genetics for health professionals in Europe (EuroGentest Project, https://www.eshg.org/index.php?id=139), which was accepted and approved by the Education Committee of the European society for human genetics in 2008.
After passing the exam, the student will be able to:
A. COGNITIVE DOMAIN – KNOWLEDGE
1. list and distinguish the types of genetic disorders as causes of diseases and medical conditions
2. list and compare the types and outcomes of genetic testing according to groups of indications
3. argue the advantages and limitations of genetic tests and methods used
4. calculate the recurrence risk of genetic disorders
5. distinguish categories of developmental anomalies and associate them to the corresponding causes
6. use the standardised terminology when describing dysmorphic features
7. distinguish the effects of gene variability on therapeutic outcome.
B.PSYCHOMOTORIC DOMAIN – SKILLS
1. recognise patients with a genetic disease or disorder, as well as increased risk for them
2. choose the appropriate method of genetic testing according to indication and genetic cause of a disease or medical condition
3. basically interpret the findings of genetic testing
4. organise genetic care by referring patients to medical genetics specialists, as well as other appropriate specialists and experts
5. apply basic communication skills in the transmission of genetic information
6. search diagnostic and educational databases of genetic diseases and disorders (OMIM, GeneReviews, Orphanet, Face2Gene, PharmGKB).
C. AFFECTIVE DOMAIN – VALUES AND ATTITUDES*
1. judge and identify the importance of making a genetic diagnosis
2. adopt the specificities of the approach to patients in medical genetics in relation to other medical specialisations
3. respect the importance of emotional, psychological, social and material consequences of genetic testing findings
4. apply the acquired knowledge and skills in providing the basic level of psychological and social support to patients and families affected by genetic disease or disorder
5. recognize the need for lifelong learning in medical genetics.
*The course Medical Genetics places special emphasis on the development of the affective domain, as it is crucial that, in addition to the mentioned specific knowledge and skills, future physicians develop awareness for the multidimensionality of genetic diseases and disorders. They not only encompass the cellular level in a patient but are also reflected in all other, higher aspects of the patient’s life, as well as those of their blood relatives and offspring. Genetics permeates all branches of medicine and all of humanity, from the structure and function of nuclear or mitochondrial DNA, a single cell, tissue, integrated organs, all the way to the psychological superstructure ofthe human body. As such, medical genetics is one of the most complex medical specialisations, as it requires the integration of all knowledge about the structuring and functioning of the human body and spirit.
COURSE CONTENT:
With the aim of purposeful and meaningful realisation of learning outcomes, classes are organized in five large thematic units that answer specific questions related to approach to a patient with a genetic disease or disorder or increased risk for them:
1. INDICATIONS FOR GENETIC TESTING
(How to recognize a person with a genetic disorder?)
P1
L2
L3
How to distinguish between genetic and non-genetic aetiology of diseases and medical conditions?
Types of genetic testing according to indications
Digital databases in medical genetics: application in clinical practice
2. TYPES OF GENETIC DISORDERS
(How to choose the proper method of genetic testing and interpret the results at a basic level?)
Disorders within genes
L4
L5
L6
S1
S2
S3
Spectrum of phenomena in autosomal dominant monogenic diseases
Autosomal recessive monogenic diseases: from patient to carrier
X-linked monogenic diseases and other rare types of inheritance
One disease – one monogenic cause
One disease – several possible monogenic causes: locus heterogeneity
One disease – several possible different causes: complex diseases
Disorders of one part or entire chromosome
L7
L8
L9
S4
L10
S5
Deviations from the normal chromosome number
Balanced structural genomic rearrangements: translocations and inversions
Reproductive genetics I: fertility disorders and pregnancy complications
Prenatal screening and diagnostics of chromosomopathies
Reproductive genetics II: prenatal diagnostics
Disorders of the (epi)genome
L11
Uniparental disomy and epimutations
3. THINKING IN PATTERNS OF CLINICAL FEATURES IN WIDE DIFFERENTIAL DIAGNOSIS
(How to direct genetic testing in persons with multiple congenital anomalies with or without intellectual disabilities?)
L12
L13
S6
P2
Classifications and causes of congenital anomalies
Basics of clinical dysmorphology
Genetics of mental development: developmental delay, intellectual disabillity and autism spectrum disorders
How to recognize patterns of multiple congenital anomalies? Human vs artificial intelligence
4. PERSONALIZED MEDICINE
(How to approach each patient individually?)
L14
L15
S7
P3
Practical pharmacogenomics
Gene therapy in clinical practice
Interpretation of results in pharmacogenomics
How to organize comprehensive patient care?
5. COMMUNICATION SKILLS IN MEDICAL GENETICS
(How to convey genetic information to a patient?)
L16
L17
P4
P5
Specific challenges in genet(h)ic counseling
Basic communication skills in medical genetics
Simulation of clinical reasoning in medical genetics
How to convey genetic information to a patient?
The concept of individual forms of teaching is based on the following:
Lectures – From clinical picture to genetic causes and diagnostic methods
Seminars - From recognising the indication to interpreting the findings of genetic testing
Practicals - Implementation of acquired competencies in one's own clinical practice
COURSE CONCEPT:
Course Medical genetics is a course of clinical reasoning, the foundations of which are based on stories about patients, from whom it all begins, specifically on those examples of genetic diseases or disorders that physicians most often encounter after graduation (examples from cardiogenetics, neurogenetics, oncogenetics, pediatric genetics, gynecology, etc.). With the aim of acquiring specific knowledge, skills and values / attitudes in medical genetics, all forms of teaching (lectures, seminars and practicals) are conducted through active learning techniques, encouraging the development of open, analytical and critical thinking. All material will be presented through case analyses (case-based learning), problem-based and experiential learning in a way that reflects the authentic form of action in clinical practice, in which the physician first meets the patient, not their molecular structure. This approach to learning and teaching, reverse to the classical way, encourages simpler and more meaningful mastery and application of basic theoretical knowledge, as well as thinking about the patient in patterns of clinical features in making a working / clinical diagnosis and directing genetic testing. Therefore, lectures, seminars and exercises will be held in an interactive environment.
1. Pereza N. Clinical Reasoning in Medical Genetics for Medical Students. First edition. 2025. Rijeka: University in Rijeka, Faculty of Medicine, Department of medical biology and genetics. Available at the Merlin e-learning platform.
2. Materials from lectures
1. Turnpenny P, Ellard S. Emery’s elements of medical genetics. 14. ed. 2011. Philadelphia: Elsevier/Churchill Livingstone.
2. Read A, Donnai D. New Clinical Genetics. Third edition. 2015. Banbury, UK: Scion Publishing Limited.
All information regarding the course, as well as materials from the lectures will be available on the Merlin e-learning platform. Students should visit the mentioned platform regularly in order to be informed in a timely manner of any facts or changes concerning the course. Furthermore, students should regularly fulfill the obligations related to course attendance and active participation in classes.
COURSE ATTENDANCE:
Classes are organized according to the schedule published on the Merlin e-learning platform and INP application. Attendance of lectures, seminars, practicals and midterm exams is mandatory and attendance records are kept separately for each student. All of the previously mentioned types of classes start at the exact time according to the specified schedule and being late is treated as absence from class. Entries / exits during classes are not allowed. A student may miss up to 30% of the hours provided separately for practicals, seminars and lectures. If a student is absent from more than 30% of class hours for each class type (5 hours of lectures, 4 hours of seminars, 4 hours of exercises), the student cannot continue to attend the course and loses the opportunity to take the final exam (0 ECTS, grade F).
ACTIVE PARTICIPATION IN CLASSES:
Since the course is implemented through forms of active learning, students must have and use the handbook Clinical Reasoning in Medical Genetics for Medical Students in all forms of classes (lectures, seminars and practicals) (either in electronic or printed version). During certain classes, students will independently use information technology, including active search and use of genetic electronic databases and artificial intelligence, freely available on the Internet. Therefore, it is recommended to use smart phones in contact form, especially during seminars and practicals.
Student assessment is carried out according to the current regulations at the University of Rijeka, and the Faculty of Medicine in Rijeka. Assessment is carried out using ECTS grading system (% / A-F) and a numerical grading system (1-5). Student progress will be evaluated and graded during classes and at the final exam. Out of a total of 100 credits, the student can achieve a maximum of 70 credits (70%) during the course in two written midterm exams, and a maximum of 30 credits (30%) in the final, structured oral exam.
I. DURING COURSE - MIDTERM EXAMS (TOTAL MAXIMUM OF 70 CREDITS):
During the course, the acquired knowledge from lectures, seminars and practicals will be assessed by two midterm exams in the form of a written test with multiple choice questions (Midterm exams I and II). At each midterm exam, the criterion for obtaining credits is at least 50% of correctly answered questions. Midterm exams I and II will be conducted onsite at the Faculty of Medicine in Rijeka.
Midterm exam I includes teaching units L2-P10, S1-5 and P1, has 40 questions and carries up to 40 credits. Writing time is 50 minutes. The number of correctly answered questions is converted into credits as follows:
Midterm exam II includes teaching units L11-17, S6-7 and P2-5, has 30 questions and carries up to 30 credits. Writing time is 40 minutes. The number of correctly resolved questions is converted into credits as follows:
Midterm repetition
Midterm exam repetitions can be accessed by students who:
• did not collect 35 credits during the classes, i.e. did not pass the midterm exam I and/or II, and/or
• were absent during the midterm I and/or II exams, and/or
• have passed the midterm exam I and/or II, but are not satisfied with the achieved credits.
In case of midterm I and/or II repetition, the final credits are those that the student achieves on the repeated midterm exam. Midterm exam repetitions can be accessed only once for each midterm exam. Repetitions are held live after the completion of regular classes in two terms, in each of which only one midterm is retaken:
Midterm I repetition – in agreement with students ----- Midterm II repetition – in agreement with students
The students can apply for repetitions of midterm exams via the e-mail address of the Secretary of the Department of medical biology and genetics no later than two days before the repetition of the midterm exams (andrea.sizgoric@uniri.hr).
II. FINAL EXAM (TOTAL MAXIMUM OF 30 EVALUATION POINTS):
The final exam cannot be accessed by students who:
• finally achieve less than 35 credits after having taken the repetition of the midterm exam I and/or II, and / or
• have 30% or more of absences from classes.
Such a student is graded with an F (unsuccessful), cannot obtain ECTS credits or take the final exam, i.e. must re-enroll the course in the following academic year.
The final exam can be accessed by students who:
• achieved ≥35 credits (50% or more of the possible 70 credits) during classes, and
• do not have more than 30% of absences from classes.
The final exam is a structured oral exam in the form of a patient management problem that will be held onsite at the Faculty of Medicine in Rijeka and consists of four patient cases that will examine the integration of knowledge, skills and values / attitudes (monogenic disorder, chromosomal disorder, dysmorphic syndrome, pharmacogenomics). The final exam is passed if the student achieves 15 out of 30 credits.
Success in the structured oral exam is evaluated and converted into credits in the following way :
III. FINAL GRADE:
The final grade is the sum of the credits collected during the course and at the final exam. Assessment within the ECTS system is carried out according to the achieved final success in the following way:
COMMUNICATION WITH TEACHERS:
Teachers are available daily during working hours via e - mail addresses (available on the webpage of the Faculty of Medicine in Rijeka) for all questions concerning the course. Consultations are possible by appointment and can be conducted live or through the online platform MS Teams.
ACADEMIC INTEGRITY:
It is expected that the teacher will respect the Code of Ethics of the University of Rijeka, and the students the Code of Ethics for students of the University of Rijeka.
List the types of genetic disorders (a1). List, compare and distinguish types of genetic testing according to groups of indications: diagnostic, predictive, carrier testing, population screening, pharmacogenomic (a2). Compare the aims and outcomes of the types of genetic testing according to the groups of indications (a2, c1). Judge and determine the importance of making a genetic diagnosis (c1). Define and distinguish between direct to consumer genetic testing and genetic testing as part of genetic counseling (a2, c2). Compare the terms genetic susceptibility and genetic determinism (a1). Associate the types of genetic testing according to indications with specific examples of diseases and conditions (a2, b1).
Describe and compare the organization of medical genetics in the Republic of Croatia and the world (b4, c2). Describe the role of medical genetics specialists and non-medical genetics specialists in the approach to a patient with a (possible) genetic disease / disorder (c2). Define the concept of genetic literacy and judge its importance in medicine (c5). List, distinguish and access diagnostic and educational databases of genetic diseases (OMIM, GeneReviews, Orphanet, Human Phenotype Ontology, Face2Gene, PharmGKB) (b6, c5).
Repeat the basic principles / criteria of autosomal dominant inheritance (a1, a4, b1). Define and divide sequence variants as the cause of genetic diseases (a1). Explain specific genetic phenomena that affect the clinical picture of autosomal dominant diseases: penetrance continuum, variable expressivity, zygosity, anticipation, later age of onset (a1, b1). Define and distinguish between locus and allelic genetic heterogeneity (a1). Evaluate the importance of determining genotype-phenotype correlation (a4, b3). Distinguish genetic testing methods according to the type of causal sequence variant and mode of inheritance: next generation sequencing (whole genome sequencing, whole exome sequencing, clinical exome sequencing), Sanger sequencing and polymerase chain reaction variants (a3).
Repeat the basic principles/criteria of autosomal recessive inheritance (a1, a4, b1). Explain the influence of sequence variants population grouping on genetic testing (a1, b2, b3). Distinguish the choice of genetic testing methods according to the groups of indications (a2, a3, b2). Define extended genomic screening for carriers (b2). Explain the mechanism of neoplasm development in autosomal dominant inherited forms of cancer (a1).
Repeat the basic principles / criteria of X-linked inheritance (a1, a4, b1). Explain the differences in the expression of X-linked diseases between women and men (a1). List X-linked diseases lethal to males (a1, a4). Explain the influence of X chromosome inactivation on the clinical picture of X-linked diseases (a1, b3). List other rare forms of inheritance (mitochondrial diseases, Y-linked inheritance) (a1).
Repeat the definitions of polyploidy and aneuploidy (a1). List and describe the clinical picture of polyploidies and the most common aneuploidies (b1). Associate polyploidies, constitutional and mosaic aneuploidies with the appropriate mechanism of occurrence and recurrence risk (a1, a4, b1). Distinguish methods of genetic testing to determine numerical chromosome disorders: GTG-method, fluorescent in-situ hybridization, quantitative fluorescent polymerase chain reaction, array comparative genomic hybridization (a3).
Define structural variations (a1). List and describe the differences between balanced structural genome rearrangements: translocations and inversions (a1). Explain the concept carriers and their possible reproductive and non-reproductive consequences (a1, a4, b1). Compare genetic testing methods for unbalanced and balanced genome rearrangements (a2, a3, b2).
Define copy number variations (a1). List and describe the differences between the types of genomic disorders: recurrent and sporadic microdeletion / microduplication syndromes (a1). Explain the genotypephenotype correlation, i.e. different influence of the types of genomic disorders on the clinical picture and recurrence risk (a1, a4, b1). List and describe the clinical picture of the most common genomic disorders syndromes (b1). Distinguish genetic testing methods for genomic disorders (a3).
List and distinguish the types of prenatal screening with regard to indications, period and objectives of implementation (a1, a2, b2). Explain the advantages and limitations of the types of prenatal screening (a3). Describe and explain invasive methods of prenatal diagnosis (b2). Judge the importance of conducting diagnostic testing in case of a positive prenatal screening test (a3, a4, b2, b3, c1).
Define uniparental disomy and epimutations (a1). State the mechanism of occurrence of uniparental disomy in the context of calculating the recurrence risk (a1, a4). Describe the clinical picture of diseases resulting from uniparental disomy and epimutation (b1). List methods for genetic testing (a2, a3).
Define and categorise congenital anomalies according to the number of affected body regions and clinical significance (a5, b1). Distinguish between structural and functional developmental anomalies (a5, a6). Distinguish between types of isolated (malformation, dysplasia, disruption and deformation) and multiple congenital anomalies (syndrome, sequence) (a5). List the groups of causes and associate them with the corresponding group of congenital anomalies (a1, a5, c5).
Define the most common dysmorphic features of the head, neck, torso and extremities (a5, a6). Describe the dysmorphic examination (a5, a6). List the dysmorphic features of the most common syndromes that occur because of genetic and chromosomal disorders (a5, b1).
Define pharmacogenomics and explain its association with pharmacodinamics and pharmacokynetics (a7). Explain the relevance of the implementation of pharmacogenetics and pharmacogenomics to clinical practice (a2, a3, c1). List and argument the basic indications for pharmacogenomic testing according to areas of clinical medicine (b1).
Define gene therapy, gene editing and silencing (a7, c5). List selected examples of gene therapy in clinical practice and genetic diseases for which it is applied (a7, b1). Define criteria for rare diseases (a1). Search the Orphanet database for orphan drugs (b6). Give examples of genetic diseases for which orphan drugs are used (a7, b1).
Identify and explain the specificities of genetic medicine in relation to other medical specialisations (b4, c1-5). Recognise the importance of the emotional, psychological, social, and material consequences of genetic testing findings (c2-4). Explain the ethical, legal, and social implications of genetic information (c1-5). Recognize the need for collaboration with other specialists and experts (b4, c5).
Identify individuals with indications for genetic testing (b1). Conclude and argue on the justification of the indication for genetic testing using anamnesis and clinical evaluation data (a2, b1). Draw and interpret family tree (b1).
Recognize and describe dysmorphic features (a5, a6, b1). Search OMIM, GeneReviews, Orphanet and Face2Gene databases (b6). Apply standardised nomenclature for dysmorphic features during dysmorphologic examination (a5, a6, b1). Select the appropriate genetic testing method (a1-3, b2). Basically interpret the findings of genetic testing (a1-3, b3). Associate genotype with phenotype (b3). Apply acquired knowledge to predict reproductive outcome and recurrence risk (a1-4, b3). Assess the complexity of diagnosis in diseases with wide differential diagnosis (a3, b3, c1, c2). Conlude about the differences in human and artificial intelligence in clinical reasoning in medical genetics (b6).
Integrate the acquired knowledge and skills in the course into the basic interpretation of genetic testing findings (a1-5, b1-b4, b6). Organize genetic care by referring the patient to medical genetics specialists as well as other appropriate specialists and experts (c4). Assess the importance of electronic databases in lifelong learning in medical genetics (c5).
Integrate the acquired knowledge, skills and attitudes in the course into conducting the integrative approach the patient with genetic disorder or disease, or an increased risk for them (a1-a7, b1-b6, c1- 5).
Integrate the acquired knowledge and skills in the course into a conversation with a patient (a1-a5, a7, b1-b5, c1-6). Apply basic principles of genetic counseling and communication skills in conversation with a patient (b5, c2). Help patients make informed decisions and choices about further care in an understandable, clear and sensitive way (b5, c2-4). Recognise and appreciate the emotional, social and material impact of genetic diagnosis on the patient and thier family (c4, c5).
Make a working / clinical diagnosis based on the anamnesis and findings of clinical evaluation (a1, b1). Conclude and argue the type of inheritance using anamnesis and family tree (a1, b1). Determine the cause of a working / clinical diagnosis using OMIM and GeneReviews databases (b6). Select the appropriate genetic testing method (a1-3, b2). Basically interpret the findings of genetic testing (a1-3, b3). Associate genotype with phenotype (b3). Apply the acquired knowledge to determine the recurrence risk (a1-4, b3).
Distinguish the influence of genetic factors on the occurrence of monogenic, polygenic and complex diseases (a1). Basically interpret the predictive values of genetic testing (a1-3, b3). Evaluate the need for genetic testing for complex diseases (a1, a4, c1). Evaluate the importance of evidence-based medicine in everyday clinical practice (c4, c5).
Distinguish the influence of genetic factors on the occurrence of monogenic, polygenic and complex diseases (a1). Basically interpret the predictive values of genetic testing (a1-3, b3). Evaluate the need for genetic testing for complex diseases (a1, a4, c1). Evaluate the importance of evidence-based medicine in everyday clinical practice (c4, c5).
Causally associate balanced genome rearrangements and numerical chromosome changes with selected reproductive disorders (a1, b1). Select appropriate genetic testing methods for infertility, primary amenorrhea, and recurrent miscarriages (a1-3, b2). Basically interpret the findings of genetic testing (a1-3, b3). Apply acquired knowledge to predict reproductive outcome and recurrence risk (a1-4, b3). Determine the importance of making a genetic diagnosis in carriers of balanced genome rearrangements due to possible subjection to assisted reproduction or prenatal diagnostics (a4, b3, c1, c2)
Conclude and identify indications for prenatal diagnosis: amniocentesis and chorionic villus sampling (a2, a3, b1, b2). Distinguish the aims and outcomes of genetic testing methods used in prenatal diagnosis (a3, b2). Select the appropriate genetic testing method (a1-3, b2). Basically interpret the findings of genetic testing (a1-3, b3). Apply acquired knowledge to predict reproductive outcome and recurrence risk (a1-4, b3).
List the genetic causes of intellectual and developmental delay and autistic spectrum disorders (a1, b1). Describe the clinical picture of intellectual and developmental delay and autism spectrum disorders and associate with appropriate causes (b1). Select the appropriate genetic testing method (a1-3, b2). Basically interpret the findings of genetic testing (a1-3, b3). Apply the acquired knowledge to calculate the recurrence risk (a1-4, b3).
Search the pharmGKB base (b6, c5). Direct pharmacogenomic testing (a1-3, b1, b2). Basically interpret the findings of pharmacogenomic testing (a1-3, b2, c1, c3). Adjust therapy according to interpreted pharmacogenomic findings (b4, c1).
