This document discusses several genetic disorders including Down syndrome, Edwards syndrome, Patau syndrome, Klinefelter syndrome, Turner syndrome, and Marfan syndrome. It defines karyotyping as the process of analyzing chromosomes, and discusses aneuploidy as having an abnormal number of chromosomes and polyploidy as having more than two sets of chromosomes. It provides details on the typical features and complications of each genetic condition. The objectives cover karyotyping, nondisjunction, distinguishing various chromosomal alterations, and structural chromosome changes involved in certain disorders.
Sperm DNA Fragmentation (Oxidative stress, DNA damage and apoptosis, Test, Techniques, Relation to other semen parameters, Relationship to leucocytes, Relation to ICSI outcomes, Clinical applications, significance and limitations)
ANATOMY LAB DISSECTION, LUNGS AND HEART OF HUMAN CADAVER WITH DIFFERENT VIEWS AND LABELING OF EACH STRUCTURE IN EACH SLIDES
FOR MBBS 1ST YEAR, BDS, AND OTHER MEDICAL SCIENCES
Cri du chat syndrome, also known as chromosome 5p deletion syndrome, 5p− (said minus) syndrome or Lejeune’s syndrome, is a rare genetic disorder due to a missing part (deletion) of chromosome 5.[1] Its name is a French term (cat-cry or call of the cat) referring to the characteristic cat-like cry of affected children.[2] It was first described by Jérôme Lejeune in 1963.
Sperm DNA Fragmentation (Oxidative stress, DNA damage and apoptosis, Test, Techniques, Relation to other semen parameters, Relationship to leucocytes, Relation to ICSI outcomes, Clinical applications, significance and limitations)
ANATOMY LAB DISSECTION, LUNGS AND HEART OF HUMAN CADAVER WITH DIFFERENT VIEWS AND LABELING OF EACH STRUCTURE IN EACH SLIDES
FOR MBBS 1ST YEAR, BDS, AND OTHER MEDICAL SCIENCES
Cri du chat syndrome, also known as chromosome 5p deletion syndrome, 5p− (said minus) syndrome or Lejeune’s syndrome, is a rare genetic disorder due to a missing part (deletion) of chromosome 5.[1] Its name is a French term (cat-cry or call of the cat) referring to the characteristic cat-like cry of affected children.[2] It was first described by Jérôme Lejeune in 1963.
Chromosomal Disorders. The types of chromosomal disorders: structural, deletion or addition. Down's syndrome, Turner's syndrome, Klinefelter's syndrome, Patau syndrome. Hope this presentation will help you.
Turner syndrome (TS), sometimes referred to as congenital ovarian hypoplasia syndrome is a chromosomal disorder that is the most common sex chromosomal abnormality affecting girls and women.
It occurs in about 1 out of every 5000 live female births and affects all races and regions of the world equally. Turner syndrome is a genetic disorder, but it’s usually not inherited, except in very rare cases.
The name "Turner’s syndrome" comes from Dr. Henry Turner, the physician who first described the collection of its findings in 1938. However, it was not until 1959 that the cause of Turner syndrome was identified. This is the presentation on it.
Genomes and genetic_syndromes_affecting_movementsHimani Kaushik
Genomes and genetic syndromes affecting movements
Mendel’s work on inheritance in Pisum sativum was first published in 1866 and gave the law of inheritance. He described the concept of Modern Genetics. While Mendel’s research was with pisum sativum, the same principle of heredity that was discovered by Mendelian also apply to human and other animals because of the mechanism of heredity same for all complex forms of life.
Rosalind Franklin and Maurice Wilkins contribute to the discovery of the double-helix structure of DNA and James Watson and Francis Crick solved the structure of DNA, starting the new branch of molecular biology.
This project is completed in 2003 and expanded knowledge about the genetic basis for diseases and congenital malformation.
The impact of this project is just being realized, with new research into diagnostic and treatment techniques for genetic disorders.
According to WHO it occurs due to a defect in a single gene or set of genes.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
11. What do you call this Karyotype?
What is the abnormality?
12. Objectives:
1. What is a karyotype, and how is this
analysis performed?
2. What is nondisjunction?
3. Distinguish between the chromosomal
alterations that are involved in the
following human disorders:
Down syndrome, Patau's syndrome,
Edwards syndrome
Klinefelters syndrome, XYY syndrome
Trisomy X, Monosomy X
5. Distinguish between the 3 different
alterations in chromosome structure, and
how Cri du Chat, Fragile X, and Acute
myelogenous leukemia occur.
13. Advnaced maternal age &
diseases
Down’s syndrome
Toxaemia
Low birth weight / preterm delivery
Fetal death
14. odds of Down Syndrome based on age:
From Hook and Lindsjo:
American Journal of Human Genetics, Vol. 30, 1998,
15. How old is too old ?
“Advanced maternal age” is defined as
any expectant mother who will have
made her 35th birthday by the time
she delivers.
16. Advnaced paternal age &
diseases
Schizophrenia
Low birth weight
Fetal death
Autosomal dominant diseases:
Marfan’s Syndrome
Huntington’s Chorea and
von Willebrand Disease
17. Children of fathers aged 40 or older are nearly six
times more likely to have autism.
40. Klinefelter’sKlinefelter’s
SyndromeSyndrome
47, XXY
Male hypogonadism
1 in 850 live male births
Rarely diagnosed before puberty
Increased length between sole and pubic bone
Small testis, small external genitalia
Lack of secondary male features
55. Turner’s Syndrome
45, X0 (57%)
45, X0 / 46, XX – Mosaic Type
Most common sex chromosomal
abnormality in female
Female hypogonadism
Infancy
Edema of hand & foot
Swelling of nape of neck
CHD – Coarctation of aorta, bicuspid aortic
valve
56. Turner’s Syndrome
1:5000 live births
The only viable monosomy in humans
Genetically female
They do not mature sexually during
puberty and are sterile
Short stature and normal intelligence
98% of these fetuses die before birth
57.
58. Turner’s Syndrome
Puberty
Failure of secondary sexual character –
Breast, external genitalia
Short stature
Amenorrhea – single most important
cause
Hypothyroidism, glucose intolerance,
obesity, insulin resistance
Atrophic ovaries
66. Sex chromosomal disorder
Lyon hypothesis: Random inactivation
of one of X ch. in females.
Inactive X ch.- Barr body / Drumstick
appendages
Minimum of 30% cells should show
sex chromatin
68. Nucleus of a female
amniotic fluid cell
Top: Both X-
chromosome
territories are
detected by FISH.
Bottom: Same
nucleus stained
with Dapi.
The Barr body is
indicated by the
arrow, it identifies
the inactive X (Xi).
72. Objectives:
1. What is a karyotype, and how is this
analysis performed?
2. What is nondisjunction?
3. Distinguish between the chromosomal
alterations that are involved in the
following human disorders:
Down syndrome, Patau's syndrome,
Edwards syndrome
Klinefelters syndrome, XYY syndrome
Trisomy X, Monosomy X
5. Distinguish between the 3 different
alterations in chromosome structure, and
how Cri du Chat, Fragile X, and Acute
myelogenous leukemia occur.
With Imatinib therapy philadelphia chromosome disappears. And the patient develops a normal karyotype.
Colchicin.
Simian crease, two lines in the little finger, Mongolian face, Epicanthic fold.
Infections.
Transient Myeloproliferative syndrome and AML
Leukemic picture which over a few weeks reverses to normal without any therapy. Most commonly seen in Down’s babies.
Spectral karyotyping.
Translocation: a fragment of a chromosome is moved ("trans-located") from one chromosome to another - joins a non-homologous chromosome. The balance of genes is still normal (nothing has been gained or lost) but can alter phenotype as it places genes in a new environment. Can also cause difficulties in egg or sperm development and normal development of a zygote. Acute Myelogenous Leukemia is caused by this translocation.
From Hook and Lindsjo: American Journal of Human Genetics, Vol. 30, 1998, come the following odds of Down Syndrome based on age:
Advanced" maternal age is defined as any expectant mother who will have made her 35th birthday by the time she delivers. This term is a throw-back to the times when women married in their teens and began giving birth at a much younger age.
Advancing age of the father is known to be a significant risk factor for schizophrenia
Low birth weight / preterm delivery
Fetal death
The father's age, however, will influence the chances of other genetic (autosomal dominant) diseases, like Marfan Syndrome, Huntington Chorea, and von Willebrand Disease.
This karyotype demonstrates trisomy 18 (47, XY, +18) also known as Edward's syndrome. It is uncommon for fetuses with this condition to survive, so the incidence is only 1 in 8000 live births. It is rare for babies to survive for very long if liveborn because of the multitude of anomalies that are usually present.
Over lapping fingers and toes and rocker bottom feet.
The characteristic overlapping fingers (clenched fist) of a fetus with trisomy 18 is shown here.
This appearance is highly suggestive of trisomy 18. Note that digits 2 and 5 overlap 3 and 4.
The karyotype here demonstrates trisomy 13 (47, XX, +13) also known as Patau's syndrome. It is rare for fetuses with this condition to go to term, so it occurs in only 1 in 6000 live births. It is rare for babies to survive for very long if liveborn because of the multitude of anomalies that are usually present.
This is a prominent bilateral cleft lip associated with trisomy 13.
Post-axial polydactyly, particularly of all extremities, strongly suggests trisomy 13 (Patau syndrome). Note the extra digit on the hand shown here.
An extra finger (polydactyly) is present on this hand of an infant with trisomy 13 (Patau syndrome).
This baby with trisomy 13 has cyclopia (single eye) with a proboscis.
Along with midline defects such as cleft lip and/or palate, cyclopia, and proboscis, a baby with trisomy 13 may have holoprosencephaly, a condition in which the brain does not form two complete cerebral hemispheres. Seen here is the "alobar" form of holoprosencephaly in which there is only a single ventricle. [
Trisomy 13. Neutrophil - Blood film: Composite of neutrophils in a patient with this cytogenetic abnormality. Note elongated nuclei with atypical constrictions and multiple dumbbell projections from nuclei.
Aberrant Nuclear Projections of Neutrophils in Trisomy 13
Mohamed E. Salama , MD, Veena Shah , MD, Robert Roger Lebel , MD, FACMG, and Daniel L. VanDyke , PhD, FACMGFrom the Departments of Pathology and Medical Genetics, Henry Ford Hospital, Detroit, Mich
Accepted: October 1, 2003
----------------------------------------
A 26-year-old gravida 2, para 1 woman was referred to the Medical Genetics Clinic for consultation at 25 weeks of gestation for a questionable “double bubble” (gastric and duodenal distension proximal to a presumed atretic site) that was observed on ultrasound examination. A repeat ultrasound examination revealed a fetus growing appropriately for gestational age but with an echogenic bowel. The double bubble was not seen, but a fluid-filled structure was identified, probably representing a distended gallbladder. The family history revealed no birth defects or mental retardation. This woman's first child was alive with no abnormalities. The mother declined amniocentesis. Because of the echogenic fetal bowel, maternal blood was drawn to evaluate titers for toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex infection and to search for cystic fibrosis mutations. Because of partial French-Canadian ancestry, she was also tested for Tay-Sachs carrier status. Results of all those tests were normal or negative.
A 2750-g girl was born at 35 weeks' gestation by normal vaginal route. Apgar scores were 4 at 1 minute, 6 at 5 minutes (after intubation), and 8 at 10 minutes. Postaxial polydactyly of all 4 extremities was noted, and echocardiography for respiratory distress and hypotension revealed tetralogy of Fallot. At this point, it was thought that the child might have either Edwards syndrome or Patausyndrome. The cardiac malformation greatly compromised her condition, resulting in refractory hypotension and hypoxemia, and the family decided to withdraw ventilator support. A few hours after her death, the Genetics Laboratory reported preliminary fluorescent in situ hybridization findings consistent with trisomy 13 (Patau syndrome) (Figure, A: fluorescent in situ hybiridization image of a cell showing +13; the green signal is the 13 probe and the orange signal is the 21 probe). The final karyotype report confirmed the trisomy 13 (Figure, B). Review of a peripheral smear revealed 2 or more small threadlike projections from the nuclei in more than 80% of the neutrophils (Figure, C).
Trisomy 13 usually occurs by nondisjunction during gametogenesis. The prognosis is poor. Fetal death is frequent, and 90% of these babies that are born alive die within 1 year. Most have severe brain anomalies (especially holoprosencephaly). Heart defects, polydactyly and other limb anomalies, facial clefting, abdominal wall defects, and kidney malformations are also common. Any affected child may have some but not all of these problems. If the child survives the early weeks, growth is slow, and healing of wounds and recovery from illness are compromised. The few who live longer do not usually walk or speak meaningfully. Thus, they are significantly more severely handicapped than most children with Down syndrome.1
Huehns et al2 reported numerous pedunculated nuclear projections attached to the surface of nuclei in neutrophils of persons with trisomy 13. Electron microscopic examination revealed the presence of chromatin in these projections. Huehns et al2 concluded that this feature is specific to trisomy 13. Walzer et al3 proposed that a finding of 2 or more projections in 15% of the leukocytes is highly suggestive of D1 trisomy. In normal females, 2% to 10% of mature neutrophils exhibit a single drumstick (nuclear projection) (Figure, D), representing the inactivated X chromosome.
A pathologist's identification of structural anomalies of the neutrophils on a blood smear can provide rapid (less than 1 hour) support to the clinical suspicion of trisomy 13. This information may assist clinicians and families facing complex decisions about life support or transport after the delivery of an infant with multiple anomalies. Even in the most advanced centers, a fluorescent in-situ hybridization report usually requires 24 hours to obtain.
ReferencesBaty, B. J. , B. L. Brent , and J. C. Carey . Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk. Am J Med Genet 1994. 49:175–188.Huehns, E. R. , M. Lutzner , and F. Hecht . Nuclear abnormalities of the neutrophils in D1 (13–15) trisomy syndrome. Lancet 1964. 13:589–590.Walzer, S. , P. S. Gerald , G. Breau , D. O'Neill , and L. K. Diamond . Hematologic changes in the trisomy syndrome. Pediatrics1966. 38:419–429.
Article Citation:
Mohamed E. Salama, Veena Shah, Robert Roger Lebel, and Daniel L. VanDyke (2004) Aberrant Nuclear Projections of Neutrophils in Trisomy 13. Archives of Pathology & Laboratory Medicine: February 2004, Vol. 128, No. 2, pp. 243-244.
Pathologic Quiz Case: A 32-Year-Old Woman With an Abnormal Female Fetus at 19 Weeks of Gestation
Bo Jin , MD, Mousa A. Al-Abbadi , MD, and Karoline S. Puder , MDFrom the Departments of Pathology (Drs Jin and Al-Abbadi) and Obstetrics and Gynecology (Dr Puder), Sinai-Grace Hospital, Detroit, Mich
Accepted: July 27, 2004
------------
A 32-year-old white woman, gravida 1, para 0, was at 19 weeks of gestation. She was referred to our prenatal diagnostic center because of inability to identify fetal facial structures. No history of substance abuse, medication intake, or exposure to any toxic materials or radiation was noted. Her social, family, and past medical history was unremarkable. Ultrasound examination (Figure, A) revealed the presence of the following abnormalities: alobar holoprosencephaly (HPE), single orbit with 2 small eyes, proboscis superior to orbit, ventricular septal defect, overriding aorta, pulmonary artery atresia, and bilateral large echogenic kidneys. Amniocentesis with cytogenetic analysis revealed fetal karyotype of 47,XX,+13. The patient underwent induction, and a nonviable female fetus was delivered vaginally. The mother gave permission only for external examination of the fetus. The external examination of the fetus showed the facial anomalies with a single orbit containing 2 fused eyeballs, absence of nose, and a blind-ended proboscis superior to the orbit (Figure, B and C).
What is your diagnosis?
Pathologic Diagnosis: CyclopiaCyclopia is a congenital facial abnormality with medial monophthalmia and proboscis (tubular appendage) superior to the orbit. Historically, the term cyclops is Greek/ Latin in origin and was used to describe 1-eyed giants or monsters. The orbit may contain 1 eye (monophthalmia) or 2 fused eyeballs (synophthalmia).1 Occasionally the eyeball is completely absent (anophthalmia). These facial anomalies are usually associated with holoprosencephalic disorders of the brain. Holoprosencephaly is a malformation characterized by impaired midline cleavage of the embryonic forebrain. The HPE occurs when the prosencephalon fails to cleave sagittally into the cerebral hemispheres, transversely into the telencephalon and diencephalon, and horizontally into the olfactory and optic bulbs. Holoprosencephaly can be classified as alobar, semilobar, or lobar depending on the severity of the malformation.1 A variety of facial deformities are associated with HPE, including less severe facial dysmorphism, median cleft lip, cebocephaly, ethmocephaly, and cyclopia.1
The incidence of cyclopia is approximately 1.05 in 100 000 births including stillbirths.2 It is more common in female fetuses and is incompatible with life.3 Prenatal diagnosis can be achieved by ultrasound examination, which is usually followed by amniocentesis for fetal karyotype determination.
Chromosomal aberrations have been found in some cases of cyclopia. The common ones are trisomy 13 (Patau syndrome), as in our case, trisomy 18, and triploidy.4,5 Other chromosomal abnormalities have also been identified, including terminal deletion 7q, partial trisomy 3p(3p23-pter), monosomy 7q(7q36-pter), and deletion 11q.6–8
Many studies have also shown that malfunction of the “Sonic Hedgehog” (SHH) protein is associated with HPE, including cyclopia. This signal protein is encoded by a gene located at 7q36 and is expressed in the medial neural plate and ventral neural tube. This SHH protein–signaling pathway involves attachment of cholesterol and mediation by another group of genes called GLI genes.9Matsumoto et al10 and Roessler et al11 have demonstrated that a mutation of the GLI2 gene, found on 2q14, is linked to the occurrence of HPE. In addition, some animal studies suggested that disruption of cholesterol transport may play a role in the development of HPE through interference with protein signaling of the SHH gene family.12 However, whether this cholesterol transport hypothesis applies to humans is still uncertain and is a potential venue for further research.
However, in some cases of cyclopia, an associated chromosomal abnormality cannot be found. Multiple conditions and agents have been incriminated as possible etiologic factors, such as maternal rubella viral infection, drug ingestion, radiation, and other factors associated with altered gene stability. Rare cases have been reported with normal chromosomal analysis in mothers using contraceptive pills or aspirin in the first trimester.13,14
Therefore, and because chromosomal anomalies are pleiotropic, a chromosomal abnormality should be suspected when HPE is found in association with other scalp defects, postaxial polydactyly, renal cystic disease, and malrotation. On the other hand, if the anomaly is seen only in the central nervous system, a nonchromosomal etiology is favored.
In summary, cyclopia is a congenital facial dysmorphism usually associated with HPE. The possible underlying causes are heterogeneous. Prenatal diagnosis by ultrasound and cytogenetic studies are achievable at early stages of pregnancy.
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Bo Jin, Mousa A. Al-Abbadi, and Karoline S. Puder (2005) Pathologic Quiz Case: A 32-Year-Old Woman With an Abnormal Female Fetus at 19 Weeks of Gestation. Archives of Pathology & Laboratory Medicine: January 2005, Vol. 129, No. 1, pp. e19-e20.
Trisomy 13. Neutrophil - Blood film: Composite of neutrophils in a patient with this cytogenetic abnormality. Note elongated nuclei with atypical constrictions and multiple dumbbell projections from nuclei.
This is Klinefelter's syndrome with a 47, XXY karyotype. A non-dysjunctional event in meiosis (maternal or paternal) left two X chromosomes in an ovum or a sperm. This is relatively common (about 1 in 500 males). Affected males are usually normal, though they may be tall and have small testes. Infertility results from absent sperm. About half have gynecomastia. About 10% of cases are mosaics and are less affected.
Klinefelter syndrome (47,XXY) 16-year-old boy; presenting symptom delayed puberty, female fat distribution (more fat around hips), horizontal border of pubic hair, slight gynecomastia, no beard growth, absent body hair; voice broken. Testicular volume 4 ml.Laboratory values: testosterone 6.5 nmol/l; FSH 17.8 U/l; LH 14.9 U/lTreatment: testosterone substitution, e.g. with testosterone enanthate 250 mg every 3 weeks i.m.
Klinefelter Syndrome (47,XXY). 21-year-old male, noticed at medical examination for military service because of testicular volume of 2 ml. The sparse virile hair (horizontal upper border of pubic hair, absent hair on trunk and legs, practically no beard growth), gynecomastia (with lipomastia) and female fat distribution stand out. The lower body segment is distinctly longer than the upper body segment. Normal male voice.Laboratory values: testosterone 10.5 nmol/l (low), LH 14.2 U/l, FSH 25.1 U/l (clearly elevated).Treatment: testosterone substitution with Testoviron® Depot 250 mg every 3 weeks i.m.
Comments:
This testicular biopsy is from an adult male with history of normal semen volume and severe oligospermia. He had small firm testes and body habitus suggestive of Klinefelter’s syndrome. The biopsy shows small hyalinized seminiferous tubules and pseudo-adenomatous clusters of leydig cells.
Comments: Couple of hyalinized seminiferous tubules surrounded by leydig cells containing abundant microvacuolated cytoplasm. Even though leydig cells may appear morphologically normal in Klinefelter?s syndrome, they are often functionally deficient and androgen levels are often reduced accompanied by elevated FSH and LH levels.
This photomicrograph from an undescended testis shows intratubular germ cell neoplasia with testicular microliths. Isolated testicular microliths may be seen in cryptorchid testes, prepubertal Klinefelter’s syndrome, male pseudohermophrodites, and rarely in normal testes.
This photomicrograph from an undescended testis shows intratubular germ cell neoplasia with testicular microliths. Isolated testicular microliths may be seen in cryptorchid testes, prepubertal Klinefelter’s syndrome, male pseudohermophrodites, and rarely in normal testes.
[altered colours] Cover design: The front cover of Human Reproduction: shows the results of fluorescence in-situ hybridization analyses of a Klinefelter syndrome patientÕs spermatozoa and spare preimplantation embryos using DNA probes specific for chromosomes X (green) Y (red) and 18 (orange). An abnormal sperm nucleus XY18 is shown (top left) along with abnormal nuclei from one chaotic embryo: XXYY1818 (top right), X1818 (bottom left), Y18 (bottom right). The frequency of sex chromosome hyperploidy in the spermatozoa of the Klinefelter patient was higher than normal. Only 3 out of the 10 spare embryos were normal for the chromosomes tested.
Human Reproduction Vol15. no2. pp 440-444, 2000.
This is monosomy X (Turner's syndrome, with karyotype 45, X). It is uncommon for fetuses with monosomy X to survive. However, women with Turner's syndrome can live relatively normal lives, though they are unable to bear children.
One very characteristic feature of a fetus with monosomy X is the "cystic hygroma" of the neck. This is not a true neoplasm, but represents failure of lymphatics to form and drain properly. It is this structure that eventually forms the "web neck" feature of women with Turner's syndrome. Note the grey coloration from prolonged intrauterine demise.
One very characteristic feature of a fetus with monosomy X is the "cystic hygroma" of the neck. This is not a true neoplasm, but represents failure of lymphatics to form and drain properly. It is this structure that eventually forms the "web neck" feature of women with Turner's syndrome. Note the grey coloration from prolonged intrauterine demise.
One very characteristic feature of a fetus with monosomy X is the "cystic hygroma" of the neck. This is not a true neoplasm, but represents failure of lymphatics to form and drain properly. It is this structure that eventually forms the "web neck" feature of women with Turner's syndrome. Note the grey coloration from prolonged intrauterine demise.
One very characteristic feature of a fetus with monosomy X is the "cystic hygroma" of the neck. This is not a true neoplasm, but represents failure of lymphatics to form and drain properly. It is this structure that eventually forms the "web neck" feature of women with Turner's syndrome. Note the grey coloration from prolonged intrauterine demise.
One very characteristic feature of a fetus with monosomy X is the "cystic hygroma" of the neck. This is not a true neoplasm, but represents failure of lymphatics to form and drain properly. It is this structure that eventually forms the "web neck" feature of women with Turner's syndrome. Note the grey coloration from prolonged intrauterine demise.
The "streak ovaries" of Turner's syndrome are shown here. Bilaterally below the fallopian tubes at the top of the photograph are long thin bands of tan ovarian tissue in this 55-year-old woman. No ova were ever present.
Nucleus of a female amniotic fluid cell. Top: Both X-chromosome territories are detected by FISH. Shown is a single optical section made with a confocal microscope. Bottom: Same nucleus stained with Dapi and recorded with a CCD camera. The Barr body is indicated by the arrow, it identifies the inactive X (Xi). Preparation of specimen as described in: R Eils, S Dietzel, E Bertin, E Schrock, MR Speicher, T Ried, M Robert-Nicoud, C Cremer and T Cremer (1996): Three-dimensional reconstruction of painted human interphase chromosomes: active and inactive X chromosome territories have similar volumes but differ in shape and surface structure. Journal of Cell Biology, Vol 135, 1427-1440. PMID:8978813
[Original image] Cover design: The front cover of Human Reproduction: shows the results of fluorescence in-situ hybridization analyses of a Klinefelter syndrome patientÕs spermatozoa and spare preimplantation embryos using DNA probes specific for chromosomes X (green) Y (red) and 18 (aqua). An abnormal sperm nucleus XY18 is shown (top left) along with abnormal nuclei from one chaotic embryo: XXYY1818 (top right), X1818 (bottom left), Y18 (bottom right). The frequency of sex chromosome hyperploidy in the spermatozoa of the Klinefelter patient was higher than normal. Only 3 out of the 10 spare embryos were normal for the chromosomes tested.