Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging. It is caused by a mutation in the LMNA gene which leads to production of a defective protein called progerin. Children with HGPS appear normal at birth but start exhibiting aging-related problems at a very early age. They experience severe failure to thrive, loss of body fat and hair, stiff joints, and cardiovascular complications leading to death usually in their teens. The only approved treatment is lonafarnib which works by inhibiting progerin production and has shown benefits in improving growth and reducing disease severity. A multidisciplinary care approach is needed to manage the various health issues associated with H
Majority of cancer lead by point mutation in p53 gene. which is also known as "guardian of genome". this mutation leads conversion of normal cell into cancerous cell.
PREMATURE AGING SYNDROMES AND THEIR CLINICAL MANIFESTATIONSDR. MOHNISH SEKAR
Aging is an inevitable consequence of human life resulting in a gradual deterioration of cell, tissue and organismal function and an increased risk to develop chronic ailments. Premature aging syndromes, also known as progeroid syndromes, recapitulate many clinical features of normal aging and offer a unique opportunity to elucidate fundamental mechanisms that contribute to human aging. Progeroid syndromes can be broadly classified into those caused by perturbations of the nuclear lamina, a meshwork of proteins located underneath the inner nuclear membrane (laminopathies); and a second group that is caused by mutations that directly impair DNA replication and repair.
Childhood Poikiloderma may have varied clinical manifestation, so a proper clinical history and examination is required to rule out differential diagnosis for the etiology and management.
Majority of cancer lead by point mutation in p53 gene. which is also known as "guardian of genome". this mutation leads conversion of normal cell into cancerous cell.
PREMATURE AGING SYNDROMES AND THEIR CLINICAL MANIFESTATIONSDR. MOHNISH SEKAR
Aging is an inevitable consequence of human life resulting in a gradual deterioration of cell, tissue and organismal function and an increased risk to develop chronic ailments. Premature aging syndromes, also known as progeroid syndromes, recapitulate many clinical features of normal aging and offer a unique opportunity to elucidate fundamental mechanisms that contribute to human aging. Progeroid syndromes can be broadly classified into those caused by perturbations of the nuclear lamina, a meshwork of proteins located underneath the inner nuclear membrane (laminopathies); and a second group that is caused by mutations that directly impair DNA replication and repair.
Childhood Poikiloderma may have varied clinical manifestation, so a proper clinical history and examination is required to rule out differential diagnosis for the etiology and management.
Abstract—Hutchinson–Gilford Progeria Syndrome is a rare genetic disorder characterized by premature aging involving the skin, bones, heart, and blood vessels. We report a five year old female child with clinical manifestations characteristic of this syndrome. This child had a senile look with large cranium, frontal bossing, sparse light brown hair and dilated visible veins over the scalp. Other features were prominent eyes, beaked nose, micrognathia, sclerodermatous changes in both feet and legs, laxed and atrophic skin over dorsum of both hands and mottled pigmentation over trunk. Decreased high-density lipoprotein (HDL) levels was characteristic of the syndrome. This case is reported for its rarity and uncommon relationship with hypothyroidism.
A genetic disease is any disease caused by an abnormality in the genetic makeup of an individual. The genetic abnormality can range from minuscule to major - from a discrete mutation in a single base in the DNA of a single gene to a gross chromosomal abnormality involving the addition or subtraction of an entire chromosome or set of chromosomes. Some people inherit genetic disorders from the parents, while acquired changes or mutations in a preexisting gene or group of genes cause other genetic diseases. Genetic mutations can occur either randomly or due to some environmental exposure.
Similar to Hutchinson-Gilford Progeria Syndrome (20)
Atrial fibrillation is the most common type of cardiac arrhythmia. It is the leading cardiac cause of stroke
https://www.youtube.com/watch?v=4pSobW-a6gQ&list=PL2XcrMWxPBLQyEdWnJuO4qSI2m-WTrglH&pp=gAQBiAQB
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic inflammatory neuropathy. CIDP is diagnosed according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria
https://www.youtube.com/watch?v=AYEhL1LdONY
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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
3. Hutchinson-Gilford progeria syndrome (HGPS) is characterized by
clinical features that develop in childhood and resemble some
features of accelerated aging. Death occurs as a result of
complications of severe atherosclerosis, either cardiac disease
(MI or HF) stroke, generally between ages six and 20 years.
Average life span is approximately 14.5 years.
6. diseases associated with mutations in genes encoding DNA repair
disease discreption gene
Werner syndrome Short stature, skin tightness and ulcerations, hair
greying, lipodystrophy, osteoporosis, bilateral
cataracts, heart disease, and calcification of cardiac
valves
WRN
Bloom syndrome Prenatal growth retardation, light sensitivity,
telangiectatic skin lesions, reduced fertility,
predisposition to cancer, and immunodeficiency
BLM
Rothmund-Thomson
syndrome
Greying of hair, juvenile cataracts, and skin and
skeletal abnormalities
RECQL4
Cockayne syndrome Impaired development of the neural system,
microcephaly, photosensitivity and premature ageing
ERCC6,
ERCC8
Xeroderma
pigmentosum
Skin photosensitivity, photophobia and no neurological
abnormalities
XPA,
XPB,
XPC,
XPG
Ataxia telangectesia Progressive cerebellar degeneration, pigmentary ATM
7. diseases associated with mutations in genes encoding DNA repair
Disease discreption gene
Ataxia telangectesia
like disorder
Progressive cerebellar degeneration, ataxia and
oculomotor apraxia, but no immunodeficiency nor
telangiectases
MRE11
A
Nijmegen breakage
syndrome
Progressive microcephaly, intrauterine growth
retardation, short stature, recurrent sinopulmonary
infections, increased cancer risk and premature
ovarian failure
NBN
cerebroretinal
microangiopathy with
calcifications and
cysts
Progressive intracranial calcifications, brain cysts,
leukodystrophy, spasticity, ataxia, cognitive decline,
osteopenia and bone fractures
CTC1
dyskeratosis
congenita
Bone marrow failure, abnormal skin pigmentation,
cancer predisposition, pulmonary and hepatic fibrosis,
leukoplakia, nail dystrophy, thrombocytopenia,
premature hair greying, osteoporosis and testicular
atrophy
TERC,
TERT,
WRAP5
3
Seckel syndrome MR and postnatal dwarfism with a small, birdlike face ATR
8. Progeroid laminopathies
disease discreption Gene
HGPS
atypical progeroid syndromes Short stature, prominent nose,
premature hair greying, partial alopecia,
skin atrophy, lipodystrophy and skeletal
anomalies
LMNA
mandibuloacral dysplasia type A Growth retardation, skeletal and
craniofacial anomalies, osteolysis,
pigmentary skin changes and partial
lipodystrophy
LMNA
9. Other progeroid syndromes
disease discreption gene
restrictive dermopathy Intrauterine growth retardation, facial
deformities, enlarged fontanelles, tightly
adherent skin, low bone density,
dysplasia of clavicles and congenital
contractures
ZMPSTE24
mandibuloacral dysplasia
type B
Generalized lipodystrophy, prominent
eyes, beaked nose, hair loss, mottled
hyperpigmentation, acro-osteolysis and
joint contractures
ZMPSTE24
Néstor-Guillermo progeria
syndrome
Early onset, lipoatrophy, severe
osteolysis and alopecia
BANF1
12. A. Diseases of Striated Muscle
1. AD Emery-Dreifus Muscular Dystrophy
2. AR Emery-Dreifus Muscular Dystrophy
3. AD Cardiomyopathy Dilated 1A
4. AD Limb Girdle Muscular Dystrophy Type 1B
B. Peripheral Neuropathy
1. AR Charcot-Marie-Tooth Disorder Type 2B1
C. Lipodystrophy Syndromes
1. AD Dunnigan-type Familial Partial Lipodystrophy
2. AD Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic
Cardiomyopathy and Leukomelanodermic Papules
3. AR Mandibuloacral Dysplasia
D. Accelerated Aging Disorders
1. AD Atypical Werner Syndrome
2. AD Hutchinson-Gilford Progeria Syndrome
3. AD Restrictive Dermopathy Lethal
14. HGPS is an ultra-rare, sporadic, AD orphan disease, without
gender or ethnic propensity.
This progressive, degenerative disorder has onset in early
childhood with an estimated overall prevalence of 1 in 6-8
millions, and therefore 300–350 children were estimated to be
living with progeria worldwide in 2014.
19. HGPS is caused by an AD de novo mutation in the LMNA gene
(1q22) which encodes A-type lamins (An inner nuclear membrane
proteins that play roles in nuclear structure and shape), this
mutation amplifies a cryptic splice event in exon 11 leading to
deletion of 50 AA of the prelamin A precursor protein.
This deletion removes the recognition site for the
metalloproteinase ZMPSTE24 in the prelamin A and leads to the
production of a truncated protein called progerin. Progerin
production results in an aberrant nuclear shape and the
dysregulated expression of hundreds of genes
23. 1. Features of accelerated aging
2. Growth deficiency. failure to thrive. Poor weight gain and loss
of subcutaneous fat. Stature decreases.
3. Characteristic facial features include
A. Head is disproportionately large for face
B. Narrow nasal ridge with a narrow nasal tip
C. Thin vermilion of the upper and lower lips
D. Small mouth, retrognathia, and micrognathia
E. A short, thick lingual frenulum limits tongue mobility
F. Narrow airway and rigid laryngeal structures cause a high-
pitched voice.
24.
25.
26. 4. Dental. Delayed eruption and delayed loss of primary teeth.
Dental crowding occurs as a result of a small mouth, lack of
primary tooth loss, and secondary tooth eruption behind the
primary teeth.
5. Skin. Skin findings may be evident at birth and are present in
all individuals by age two years. Sclerodermatous skin
changes, dimpling or irregular small out pouchings occur over
the lower abdomen and proximal thighs. Abnormal
pigmentation consisting of light or dark macules and patches
along with some papules.
27.
28.
29. 6. Hair. Partial alopecia progresses to total alopecia. Loss of
eyebrows and loss of eyelashes in some individuals.
7. Musculoskeletal
A. The coxa valga causes a wide based shuffling gait
B. Hip dislocation because of the progressive coxa valga
C. Avascular necrosis of the hip.
D. Osteolysis of the distal phalanges
E. Short clavicles
F. Pear-shaped thorax
G. Extra skeletal calcifications are present in 40% of cases
30.
31.
32. 8. Endocrine. Sexual immaturity. No cases of fertility have been
described. Insulin resistance occurs in 50%, without
development of DM.
9. Cardiovascular. severe atherosclerosis, usually without
obvious abnormalities in lipid profiles.
A. Diastolic dysfunction is detected beyond age 5 years
B. Ventricular hypertrophy
C. HT
D. Mitral and aortic valves calcification, stenosis, and
regurgitation
E. Coronary vascular insufficiency
F. Overt HF appear late
33. 10. Cerebrovascular TIAs, silent strokes, or symptomatic strokes
(The mean age of infarction identification on neuroimaging is
6.8 years (0.4 –10.7years)
11. Ophthalmologic. Nocturnal lagophthalmos (the inability to
fully close the eyes during sleep) is common.
12. Nails become dystrophic.
13. Hearing. Conductive hearing loss is highly prevalent at all
ages.
14. Tumor rate is not increased over that of the general
population. One individual died of a chondrosarcoma of the
chest wall at age 13 years .
35. 1. Ectodermal
i. Dental. Delayed eruption and
delayed loss of primary teeth,
partial secondary tooth eruption,
dental crowding
ii. Skin. variably pigmented,
sclerodermatous, skin
outpouchings over lower
abdomen and/or proximal thighs
iii. Hair. Total alopecia, with very
sparse downy immature hair
remaining; loss of eyebrows
iv. Dystrophic nails
2. Musculoskeletal
i. Coxa valga with wide-based,
shuffling gait, sometimes
accompanied by avascular
necrosis of the femoral head
ii. Osteolysis of the distal phalanges
iii. Short clavicles with distal
resorption
iv. Pear-shaped thorax
3. Growth deficiency
i. Short stature (<3rd percentile)
ii. Poor weight gain (<3rd
percentile), weight distinctly
low for height
iii. Diminished subcutaneous body
fat globally
4. Facial features
i. Head disproportionately large
for face
ii. Long narrow nose
iii. Thin vermilion of the upper and
lower lips
iv. Retrognathia and micrognathia
5. Other
I. Thin, high-pitched voice
II. Low-frequency conductive
hearing loss
III. Nocturnal lagophthalmos
37. 1. Weight and height plotted on standard growth charts to evaluate
growth over time
2. ECG and echocardiogram
3. Carotid artery duplex
4. MRI/MRA of the brain and neck
5. Skeletal x-rays to evaluate for characteristic findings: acroosteolysis,
clavicular resorption, coxa valga, and extraskeletal calcifications
6. Dual-energy x-ray absorptiometry (DXA) to assess bone mineral
density.
7. Occupational and physical therapy assessments, including six-
minute walk test, goniometry to assess joint mobility, and
assessment of activities of daily living
8. Nutritional assessment, although dietary intake is generally not
compromised in these patients
9. Audiologic, ophthalmologic, and dental examinations
38. A, Chronic watershed (white arrows) and white matter infarcts (black arrow)
B, Acute gyral infarcts (black arrows).Bright signal in the sulci indicates slow
cortical collateral flow (white arrows).
39. Arterial calcification. CTA reformatted images of the same patient demonstrate
right VA calcification (A) and ICA and external carotid artery (B) calcifications.
40. Progerin levels in plasma (351±251 pg/mL) from
untreated patients with HGPS were on average 95-fold
higher than in non-HGPS plasma
A multigene panel that includes LMNA, ZMPSTE24, and
other genes of interest is most likely to identify the genetic
cause of the condition while limiting identification of
variants of uncertain significance and pathogenic variants
in genes that do not explain the underlying phenotype.
42. HGPS is usually diagnosed during the second year of life or
later, when progeroid features begin to be noticeable. The
diagnosis is based upon a thorough clinical evaluation,
characteristic physical findings, a careful patient history and
diagnostic genetic testing which is available through the
Progeria Research Foundation (www.progeriaresearch.org).
44. Lonafarnib
Lonafarnib is an orally active
farnesyltransferase inhibitor
is developed for the
treatment of
1) Hepatitis D virus (HDV)
infections
2) Progeria
45. Mechanism of action
Development of lonafarnib for oncology has been
discontinued due to lack of efficacy. In progeria, lonafarnib
inhibits farnesyltransferase to prevent farnesylation and
subsequent accumulation of progerin and progerin-like
proteins in the nucleus and cellular cytoskeleton.
Lonafarnib therapy significantly decreased plasma progerin
levels within 4 months
46.
47. Dose
The starting dosage of lonafarnib for patients with a BSA of
≥ 0.39 m2 is 115 mg/m2 twice daily taken with morning and
evening meals to reduce the risk of GIT adverse reactions;
after 4 months of treatment, lonafarnib dosage is to be
increased to 150 mg/m2 twice daily with morning and
evening meals. The dosage of lonafarnib dosage should be
rounded to the nearest 25 mg increment.
48. Adverse reactions
The most common adverse reactions (incidence > 50%) with
lonafarnib:
a) Vomiting (90%)
b) Diarrhoea (81%)
c) Infection (78%)
d) Nausea (56%)
e) Decreased appetite (53%)
f) Fatigue (51%)
49. Multidisciplenary team
1. Growth retardation
2. Orthopedic
3. Cardiovascular and neurological
4. Dental
5. Ophthalmological
6. Hearing aid