Suggested Sequence of Thematic Modules
(Comments and Requests for Adjustments of Contents or Sequence of Modules are Welcomed)
INTRODUCTION
CLINICAL EYE OPENERS and CEO
Goals, objectives and limitations.
Part 1 – About CEO (in English or Ukrainian, 9 min.).
Part 2 – CEO tour (in English, 17 min.; in Ukrainian, 8 min.).
DEFINITIONS OF FOUR BASIC CONCEPTS
Essence of Dysmorphology in Clinical Teratology and Genetics.
Part 1 (page in English).
Part 2 (page in English).
SIX TERMS DEFINING CLINICAL STEPS and VOCABULARY / TERMINOLOGY
Informal definitions.
Page in English.
PRINCIPLES OF TERATOLOGY
Essence of Teratology – contrasts with Toxicology and Genetics.
In English or Ukrainian, 13 min.
DYSMORPHOLOGY
START
Outline of goals, objectives, …
In English or Ukrainian, 8 min.
BASIC NOTIONS SIGN SIGNALS … TERATOGENIC MEDICATIONS
Illustration of landmarks of Clinical Dysmorphology – prototype Down syndrome.
Part 1 (in English, 40 min.).
Part 2 (in English, 47 min.).
Ukrainian Teratology Information System (site in Ukrainian).
PARTIAL MONOSOMIES or TRISOMIES Syndromes
Posted are multiple examples – see among others:
Warkany 8+ trisomy mosaicism
13q- partial deletion of the long arm of chromosome thirteen
(continued) MOSAICISMS
FISH (DNA specific diagnostic probes) – best use – why and how (21 min.)
OPTIONAL BUT IMPORTANT
Renaissance of Medical Teratology
The pioneer and first President of the first Medical Teratology Society was Dr. Josef Warkany. In a series of short interviews, Dr. Warkany outlines the initial steps of the establishment of Clinical Teratology. These presentations help us remember the basis of Teratology principles.
Series of interview in English.
Principles of Teratology (in English or Ukrainian, 13 min.).
Dysmorphology – Rules – Syndrome, FAS, etc. – Gallery
DYSMORPHOLOGY – CLINICAL PROTOTYPE
DOWN SYNDROME (DS)
Gallery – Overview of Signs
DS is among the most frequent autosomal trisomy among liveborns. Collectively, a few infants with DS will manifest a large array of common dysmorphic signs. DS is a prototype of a dysmorphic syndrome, of premature aging and of elevated cancer risk.
In English, 20 min.
DS – Signs – Virtual Clinic – Infants (Part 1)
In English or Ukrainian, 14 min.
DS – Signs – Virtual Clinic – Infants (Part 2)
In English or Ukrainian, 13 min.
DS – Signs – Virtual Clinic – Child – Adult (Part 3)
In English or Ukrainian, 11 min.
DS – Four Video Recordings – Proficiency Test
In English, 42 min.
DS – High-Arched Palate – Gallery
CLINICAL
TERATOGENS
Thalidomide
Thalidomide embryopathy was a fundamental public health disaster that demonstrated the importance of Medical Teratology and lead to laws mandating that medications are safe for the unborn (see UTIS – Ukrainian Teratology Information System). Thalidomide embryopathy mostly impacts developing limbs and ears – does not impact significantly cerebral development. One of the principles of teratology in contrast to toxicology is that teratogens have specific impacts on embryonic development (see Teratology Principles).
Part 1 (in English, 9 min.).
Part 2 (in English, 7 min.).
Cretinism – Prenatal Iodine/maternal thyroid deficiency
Iodine deficiency is a worldwide public health problem that can be prevented by fortification of salt. Likewise, fortification of flavor of folic acid can reduce at least by 50% the impact of neural tube defects (NTD) (see Prevention of Birth Defects; see Prevention of NTD in Ukraine – video 1, video 2).
Environmental factors and genetics, in this instance mountainous region, related to soil iodine deficiency, lack of fortified salt with iodine and family genotypes are determining etiologic factors. Not all family members will express cretinism. Note that all infants are screened for impacts of iodine deficiency (thyroxin) calling for early therapy to prevent mental deficits.
Gallery – cluster in an Alpine village.
Alcohol – Fetal Alcohol Embryopathy, Fetopathy, Syndrome, Spectrum Disorders (9 parts)
Alcohol is an optional “social” teratogen (100% avoidable) and also a toxin. Alcohol is arguably the most common teratogen and a cause of preventable functional and structural developmental anomalies.
Fetal Alcohol Spectrum Disorders (FASD) and Developmental Outcomes – An eminent presentation (with English or Ukrainian slides, 31 min.).
FASD – Clinical diagnosis, care and prevention – World perspective – Authoritative video
Perspective by the Director of National Institute on Alcohol Abuse, Bethesda, MD, USA.
In English – Ukrainian, 65 min.
Radiation
Another major teratogen, mutagen, and carcinogen (oncogene). The main impacts on human population stem from Medical applications, atomic bomb explosions, the Lenin nuclear power plant explosion in Chornobyl, the nuclear plant explosion in Fukushima in Japan and numerous accidents in nuclear power plants across the world.
Lecture in Ukrainian, 32 min.
Lecture – New York Academy of Medicine – in English or with French subtitles, 32 min.
DYSMORPHOLOGY in CLINICAL PRACTICE and PRACTICUMS
Dysmorphology physical examination of a neonate
In English, 25 min.
Dysmorphology physical examination of a child
In English, 27 min.
Dysmorphology physical examination of a child with FASD
In English, 21 min.
Dysmorphic Signs – FASD?
In English, 18 min.
Dysmorphic Signs – FASD?
In English, 15 min.
Dysmorphic Signs – FASD?
In English, 27 min.
Diagnosis of the Fetal Alcohol Syndrome – An eminent presentation
With English or Ukrainian slides, 33 min.
Auricles (Visible Component of Ears)
A common signal of renal anomalies – Gallery.
Diagnosis Dilemma and Homage of Dr. Helen E. Nash
In English, 12 min.
HANDS – FEET – FINGERS – TOES
Brother – Sister Finger Tapering and Developmental Anomalies
A gallery
CLINICAL PROTOTYPES
AUTOSOMAL DOMINANT
The Habsburg Saga – the Family History is Diagnostic – A “Real Game of Thrones”
The family history along argues of abuse, cruelty, criminality, non-paternity …
Neurofibromatosis peripheral type I (NF-1)
Mutation of one of the largest human genes manifested in an autosomal dominant phenotype. The clinical spectrum is variable and the scope very wide. NF-1 is a high cancer risk condition with prenatal and postnatal manifestations progressive in nature. The penetrance is high but manifestations may be settle and late.
Neurofibromatosis-1 Complex – Acromegaly – Gallery
Achondroplasia
A fibro – chondro – skeletal – autosomal – dominant – disorder, one of the most common causes of disproportional short stature. The penetrance is high. The grease of short stature may be moderate or severe (variability). Connective tissue laxity in combination with disproportionally large head is dangerous particularly during and after birth (apnea, cord injury …). Most severe instances may be due to other genes mutations (achondrogenesis). Most de-novo mutations are of paternal origin and reflect the impact of aging (a Down syndrome, the association with maternal aging).
In English, 13 min.
CLINICAL PROTOTYPES
AUTOSOMAL RECESSIVE
Morquio or Mucopolysaccharidosis IV (MPS)
CLINICAL PROTOTYPES
AUTOSOMAL TRYSOMIES
Edward Syndrome Associated with Trisomy 18 (18+)
CLINICAL PROTOTYPES
AUTOSOMAL PARTIAL CHROMOSOME DELETIONS
13q- Principles and cancer risk
13q- Multiple Malformations Complex
CLINICAL PROTOTYPES
MOSAICISMS
McCune-Albright Polyostotic Fibrous Dysplasia – Gallery
CLINICAL PROTOTYPES
THE MIDLINE – MEDIAN
Midline (median) tooth
Anomalies of the midline often are the signal of alterations shortly after fertilization (Blastogenesis).
In English, 14 min.
Blastopathies
Malformations prior to embryogenesis – bilateral and of the midline (twinning, Neural Tube Defects (NTD), omphalocele …).
Parts 1, 2 and 3 (pages in English).
CLINICAL SEMIOLOGY
Semiology is the clinical discipline and art to recognize signs as signals of pathogenesis and/or of maldevelopment and diseases (the prototype is Down syndrome).
In English, 16 min.
CLINICAL CARDINAL SIGNS
Hypotonia
Cardinal sign of many syndrome in particular Down, Prader-Willi, …
In English or Ukrainian, 19 min.
Progressive skin signs.
Albinism Oculo – Cutaneous Partial Chediak – Higashi – Gallery.
MALFORMATIONS and HIGH CANCER RISK
(also see Down, NF-1 …)
Macroglossia – Omphalocele or Beckwith-Wiedemann syndrome
A precedent setting association of malformations with cancer risk, growth factors, etc. The cancer risk diminishes after the first decade. Anticipatory diagnosis and prevention of cancer is essential.
Gallery.
Macroglossia Perspectives and Clinical Video
In English, 28 min.
Teratoma Sacral
These malformed tissues may be malignant at birth or become malignant soon thereafter – a reason for the imperative to resect them whenever possible.
Gallery.
Muco-Cutaneous Melanic Spots
Lip spots may signal hamartomatous polyposis and cancer risk.
DEFORMATIONS
Deformations, Torticollis, etc.
Gallery.
Plagiocephaly.
Sign.
Torticollis.
Sign.
PATIENTS
SELECTIVE EXAMPLES
Bilateral anophthalmia
Illustrates the contrast of isolated from multiple developmental anomalies.
Gallery.
Fetal Alcohol Spectrum Disorders (FASD)
Gallery.
Footling Breech Legs Syndrome
Illustrates extra embryonal mechanical causes of deformations.
Gallery.
Dysmorphic Syndrome
Illustrates how few facial signs (facies) may accelerate a diagnosis.
Video in English, 15 min.
Male Turner Noonan
Illustrates the notion of phenocopy – similar array of concurrent dysmorphic signs and malformations reflecting impacts on pathogenesis by different causes (etiology). Turner syndrome in females often is due to anomalies of an X-chromosome.
Gallery.
Patau Syndrome (2 patients)
Strictly speaking, Patau syndrome describes a cluster of anomalies associated with trisomy 13. 13+ syndrome should be only applied to patient with proven trisomy 13. The main characteristic signs are those associated with holoprosencephaly (microphthalmia, midline facial clefts – see the galleries). Another two important points are: other causes result in similar syndromes and the syndromes are largely lethal (teratothanasia).
Patient 1 (gallery).
Patient 2 (gallery).
Partial deletion (monosomy) 18p-
This patient illustrates the role of Cytogenetics in the study and definition of complex and variable multiple malformations dysmorphic syndromes. Furthermore, this example also illustrates the importance of concurrent assessment of parents and siblings.
In English, 4 min.
PREVENTIVE MEDICINE and PUBLIC HEALTH
Worldwide Prevention of Human Disabilities
Virtually all civilized and advanced societies sustain programs to prevent preventable human maldevelopment. In Europe, there are over 30 population based congenital malformation monitoring systems in members of the EU and in Ukraine.
In English, 12 min.; or Ukrainian, 13 min.
Clinical Epidemiology in Practice
Developmental anomalies are leading cause of infant mortality. Among the leading teratogenes in Ukraine are ionizing radiation, alcohol, and probably wide spread micro-nutrition deficiencies, including those associated with neural tube defects such as spina bifida, among others. The focus of this presentation is on the research platform of Medword OMNI Net sustains population based registries of births and developmental anomalies. In English or Ukrainian, 35 minutes.
DRUGS PREGNANCY AND LACTATION
(also see Ukrainian Teratology Information System (site in Ukrainian)
Teratology information – categorization of drugs
Drugs may be teratogenic and breast feeding may further negatively impact child development.
In English, 7 min.
SELECTED NOTES and CLINICAL PEARLS in BRIEF
(from a large list)
What is health? – What is disease?
The clue to these important concepts is?
Women age differently from men in particular …?
The clue relates to meiosis …
Face – facies … is yours significant?
Can facies predict a future?
Abnormal function – structure.
Which is more frequent?
Mental vision
Does it exist?
Normal
What is it?
Bias vs. Open mind
Impact on Diagnosis.
Variants can be normal and normal can be variants
True?
MASTER PRESENTATION BY EXPERTS
TERATOLOGY and NEONATOLOGY in UKRAINE
In Ukraine Chornobyl radiation may be a teratogen.
Video lecture, in Ukrainian, 51 min.
HUNDREDS of UKRAINIAN CHILDREN ARE NOT IN SCHOOL – THEY ARE DEAD AND COULD BE ALIVE
Not preventing what is preventable is a crime against humanity.
Video in English or Ukrainian, 4 min.
MY CHILD MAY DIE OR LIVE PARALYZED – IT COULD HAVE BEEN PREVENTED
From the perspective of parents and neurosurgeons.
Video in Ukrainian, 7 min.
FETAL ALCOHOL SPECTRUM DISORDERS IN UKRAINE AND THE WORLD
Perspectives by the Director of the National Institute on Alcohol Abuse, NIH, Bethesda, MD, USA.
Video lecture in English-Ukrainian, 1 h. 5 min.
