Diseases of Infancy and Childhood Flashcards
Time Frames for Development:
- Neonatal period =
- Infancy =
- Age 1 to 4 years =
- Age 5 to 14 years =
- Neonatal period = the first 4 weeks of life
- Infancy = the first year of life
- Age 1 to 4 years = toddler/preschool
- Age 5 to 14 years = school age
Causes of Death For Younger than 1 Year:
- CONGENITAL MALFORMATIONS, DEFORMATIONS, AND CHROMOSOMAL ANOMALIES
- DISORDERS RELATED TO SHORT GESTATION AND LOW BIRTH WEIGHT (PREMATURITY)
- SUDDEN INFANT DEATH SYNDROME (SIDS)
- Newborn affected by maternal complications of pregnancy
- Accidents (unintentional injuries)
- Newborn affected by complications of placenta, cord, and membranes
- Bacterial sepsis of newborn
- RESPIRATORY DISTRESS OF NEWBORN
- Diseases of the circulatory system
- Neonatal hemorrhage
Causes of Death For 1-4 Years:
- Accidents (unintentional injuries)
- CONGENITAL MALFORMATIONS, DEFORMATIONS, AND CHROMOSOMAL ABNORMALITIES
- Assault (homicide)
- MALIGNANT NEOPLASMS
- Diseases of the heart
Causes of Death For 5-9 Years
- Accidents (unintentional injuries)
- MALIGNANT NEOPLASMS
- CONGENITAL MALFORMATIONS, DEFORMATIONS, AND CHROMOSOMAL ABNORMALITIES
- Assault (homicide)
- INFLUENZA AND PNEUMONIA
Causes of Death For 10-14 Years
- Accidents (unintentional injuries)
- MALIGNANT NEOPLASMS
- Intentional self-harm (suicide)
- Assault (homicide)
- CONGENITAL MALFORMATIONS, DEFORMATIONS, AND CHROMOSOMAL ANOMALIES
What represents primary errors of morphogenesis?
- Examples?
Malformations
- Ex. Extra fused thumb
- Ex. Cleft pallate
- Ex. Severe central mid face defect
Result from secondary destruction of an organ or body region that was previously normal in development. (not usually heritable)
- Example?
Disruptions
- Ex. Amniotic band syndrome
Localized or generalized compression of the growing fetus by abnormal biomechanical forces. This “uterine constraint” leads eventually to a variety of structural abnormalities.
- Example?
Deformations
(maternal, fetal, placental)
- Ex. Endometrial cavity obstructed with tumors
Cascade of anomalies triggered by one initiating aberration
- Example?
Sequences
Ex. Oligohydramnios (potter sequence)
Describes the absence of an opening, usually of a hollow visceral organ, such as the trachea and intestine
Atresia
Refers to the complete absence of an organ and its associated primordium
Agenesis
Refers to the absence of an organ but one that occurs due to failure of growth of the existing primordium
Aplasia
What the 3 major categories of congenital anomalies?
- Genetic
- Environmental
- Multifactorial
Frequencies of Congenital Anomalies:
Genetic:
- Chromosomal aberrations = ?
- Mendelian inheritance = ?
- Chromosomal aberrations = 10-15%
- Mendelian inheritance = 2-10%
Frequencies of Congenital Anomalies:
Environmental:
- Maternal/Placental Infections = ?
- Maternal Disease States (Diabetes, PKU, Endocrinopathies) = ?
- Drugs and chemicals = ?
- Irradiations = ?
- Maternal/Placental Infections = 2-3%
- Maternal Disease States = 6-8%
- Drugs and chemicals = 1%
- Irradiations = 1%
Frequencies of Congenital Anomalies:
Multifactorial: ?
Multifactorial = 20-25%
Frequencies of Congenital Anomalies:
Unknown: ?
Unknown = 40-60%
2 General Principles Affecting the Pathogenesis of Congenital Anomalies
- The timing of the prenatal teratogenic insult has an important impact on the occurrence and the type of anomaly produced.
(Embryonic vs fetal) - Interplay between environmental teratogens and intrinsic genetic defects is exemplified by the fact that features of dysmorphogenesis caused by environmental insults can often be recapitulated by genetic defects in the pathways targeted by these teratogens.
Embryonic period when most congenital anomalies occur?
3rd to between the end of the 8th week
Critical embryonic period for:
- CNS = ?
- Heart = ?
- Arms = ?
- Eyes = ?
- Legs = ?
- Teeth = ?
- Palate = ?
- External genitalia = ?
- Ears = ?
- CNS = 3- end of 5 weeks
- Heart = 3-6 week
- Arms = 4-7 weeks
- Eyes = 4-8 weeks
- Legs = 4 - end of 7 weeks
- Teeth = 6 - 8 weeks
- Palate = 6- 9 weeks
- External genitalia = 7-9 weeks
- Ears = 4-9 weeks
Defined by a gestational age less than 37 weeks, is the second most common cause of neonatal mortality, behind only congenital anomalies
Prematurity
Risk factors for prematurity?
- PPROM (preterm premature rupture of membrane)
- Intrauterine infection
- Uterus/cervix/placental abnormalities
- Multiple gestation
Hazards of prematurity?
- RDS (respiratory distress syndrome/hyaline membrane disease)
- NEC (Necrotizing Enterocolitis)
- Sepsis
- Intraventricular and germinal matrix hemorrhage
Small for GESTATIONAL age (SGA) = ?
1. Etiology (cause) –> maternal, fetal, placental
- Pathogenesis (infection, chromosomal, preeclampsia)
- Morphology (structural alterations specific to pathogenesis)
- Specific clinical manifestations/functional derangements related to this and prematurity
Fetal Growth Restriction
Fetal Growth Restriction:
Fetal influences are those that intrinsically reduce growth potential of the fetus despite an adequate supply of nutrients from the mother
- Prominent among such fetal conditions = ?
- Chromosomal disorders
- Congenital anomalies
- Congenital infections
Fetal Growth Restriction:
Placental influences:
- Adequate placental growth in the preceding mid trimester is important because during the third trimester, fetal growth places heavy demands on the uteroplacental blood supply
- Uteroplacental insufficiency is an important cause of growth restriction. This insufficiency may result from ?
- Placental causes of FGR tend to result in ASYMMETRIC growth retardation of the fetus with relative sparing of the brain
- Umbilical - placental vascular anomalies
- Placental abruption
- Placenta previa
- Placental thrombosis and infarction
- Placental infection
- Or multiple gestations
Fetal Growth Restriction:
Maternal Influences:
- The most common factors associated with SGA infants are the maternal conditions that result in decreased placental blood flow
- Vascular diseases like ? and ? are often the underlying cause
- Include thrombophilias such as ?
- Inherited diseases of hyper coagulability
- Narcotic abuse, alcohol intake, heavy cigarette smoking
- Malnutrition (esp prolonged hypoglycemia)
- Preclampsia and chronic hypertension
- Acquired Antiphospholipid Antibody Syndrome
Neonatal Respiratory Distress Syndrome:
- Pathophysiology = ?
- Morphology = ?
- Clinical features = ?
• Pathophysiology
- Fundamental defect is deficiency of pulmonary surfactant. Congenital deficiency caused by mutations in SFTPB and SFTBC genes
- Treatment = glucocorticoids
• Morphology
- There is alternating atelectasis and dilation of the alveoli.
- Eosinophilic thick hyaline membranes lining the dilated alveoli
• Clinical features
- Tachypnea
- Grunting
- Peripheral cyanosis
- Retractions
- Hypoxemia
- Ground glass infiltrates (seen in lung radiology0 caused by reticulogranular densities
RDS:
- High concentration of ventilator administered oxygen for prolonged period is associated with 2 complications?
- Retrolental Fibroplasia
2. Bronchopulmonary Dysplasia
RDS:
Bronchopulmonary dysplasia (BPD) –> ? cytokines –> Arrest ? development
- Proinflammatory cytokines (TNF, IL-1B, IL-6, IL-8)
- Alveolar
RDS:
Retrolental fibroplasia (ROP) –> ?
VEGF
- phase I = hyperoxic phase where VEGF is decreased causing endothelial cell apoptosis
- phase II= VEGF levels rebound after return to relatively hypoxic room air ventilation inducing retinal vessel proliferation characteristic of lesions in the retina
Necrotizing Enterocolitis (NEC)
• Involves what organs?
- The involved segment is distended, friable, and congested, or it can be frankly gangrenous; intestinal perforation with accompanying peritonitis may be seen.
• What do you see microscopically?
- Typically involves the terminal ileum, cecum, and right colon, although any part of the small or large intestines may be involved.
- Microscopically
- mucosal or transmural coagulative necrosis
- ulceration
- bacterial colonization
- submucosal gas bubbles may be seen
What is the most common diagnostic sign occurring in 98% of patients with Necrotizing Enterocolitis?
Pneumatosis Intestinalis (gas in the intestinal wall)
NEC
- Pathogenesis = ?
- Most cases associated with = ?
- Inflammatory mediator = ?
- Probably multifactorial
- Prematurity and enteral feeding (postnatal insult like bacteria) set in motion the cascade culminating in tissue destruction
- PAF (platelet activating factor) - increased mucosal permeability and found in increased amounts in stool and serum samples
The accumulation of edema fluid in two or more fetal compartments during intrauterine growth (pleural, peritoneal, ascites, skin)
Fetal hydrops
Fetal hydrops
- Immune
- Nonimmune
-Accumulation of fluid can be variable:
~ ? = generalized (2 or more compartments)
~ ? – localized
~ Hydrops fetalis
~ Cystic hygroma
Non-immune Hydrops:
3 major etiologies
- Cardiovascular defects – structural and functional anomalies
- Chromosomal anomalies – 45, X, and trisomies 21 and 18
- Fetal anemia (not Rh or ABO) – alpha thalassemia, transplacental Parvo
B19, twin-twin transfusion
Hemolytic disease caused by blood group antigen incompatibility between mother and fetus (Rh antigens and ABO blood groups)
Immune Hydrops
Immune Hydrops
- Pathogenesis = ?
- Of the antigens included in the Rh system, only the ? antigen is a major cause of Rh incompatibility
- The incidence of maternal Rh isoimmunization has decreased since the use of ?
- The initial exposure to Rh antigen evokes the formation of IgM antibodies, that unlike IgG antibodies, do not cross the placenta. Thus, Rh disease is uncommon with the first pregnancy.
- D antigen is a major cause of Rh incompatibility
- Rhesus immune globulin (RhIg) containing anti-D antibodies
Immune Hydrops:
- Pathogenesis for ABO incompatibility = ?
- ABO hemolytic disease occurs almost exclusively in infants of group A or B who are born of group O moms.
- For unknown reasons, certain group O women possess IgG antibodies directed against group A or B antigens (or both) even without prior sensitization.
- So the firstborn MAY BE AFFECTED
Immune Hydrops:
- Consequences of excessive destruction of red cells in the neonate = ?
- Anemia
- Jaundice (causing kernicterus- CNS damage with yellow discoloration)
Nonimmune Hydrops
- Clinical features for mild and severe = ?
- Mild
- Pallor
- Hepatomegaly - Severe
- Intense jaundice
- Generalized edema
- Signs of neurologic injury
Nonimmune Hydrops
- Histo/morpholgy = ?
- Numerous islands of EXTRAMEDULLARY HEMATOPOIESIS are scattered among mature hepatocytes in the liver
Immune Hydrops
- Histo/morphology = ?
Erythroblastosis fetalis (left shift of RBC)
2 primary routes by which Perinatal infections are acquired?
- Transcervically (Ascending)
- Fetus acquires the infection either by inhaling infected amniotic fluid into the lungs before birth OR by passing through an infected birth canal during delivery - Transplacental (Hematologic) (via the chorionic villi)
- May occur at any time during gestation OR occassionally at the time of delivery via maternal-to-fetal transfusion (like Hep B and HIV)
Most inborn errors of metabolism are genetically inherited as ?
Autosomal recessive or X-linked traits
3 bigs inborn errors of metabolism?
- PKU
- Classic Galactosemia (GALT)
- Cystic Fibrosis (CF)
Abnormalities Suggesting Inborn Errors of Metabolism:
- General = ?
- Neurologic = ?
- GI = ?
- Eyes = ?
- Muscle, Joints = ?
- General
- Dysmorphic features
- Deafness
- Self-mutilation
- Abnormal hair
- Abnormal body or urine odor (“sweaty feet”; “mousy or musty”; “maple syrup”)
- Hepatosplenomegaly; cardiomegaly
- Hydrops - Neurologic
- Hypotonia or hypertonia
- Coma
- Persistent lethargy
- Seizures - GI
- Poor feeding
- Recurrent vomiting
- Jaundice - Eyes
- Cataract
- Cherry red macula
- Dislocated lens
- Glaucoma - Muscles, Joints
- Myopathy
- Abnormal mobility
Enzyme deficiency in PKU?
Phenylalanine Hydroxylase (PAH)
autosomal recessive
Clinical presentation of PKU?
- Severe mental retardation by 6 months
- Seizures
- Decreased pigmentation of hair and skin
- Eczema
Enzyme deficiency in Galactosemia?
Galactose-1-phosphate uridyl transferase
autosomal recessive
Clinical presentation of Galactosemia?
- Most damage to liver, eyes and brain
- Hepatomegaly
- Opacification of the lens (cataracts) within a few weeks
- CNS: loss of nerve cells, gliosis, and edema in cerebellum and medulla
- Vomiting and diarrhea with milk ingestion
- Jaundice and hepatomegaly during the first week
- Mental retardation within the first 6 to 12 months
Incidence of Cystic Fibrosis
The most common lethal genetic disease that affects Caucasian populations
(1/2500 live births).
An inherited disorder of ion transport that affects fluid secretion in exocrine glands and in the epithelial lining of the respiratory, gastrointestinal, and
reproductive tracts.
Cystic Fibrosis
Clinical Features of CF = ?
- Chronic lung disease secondary to recurrent infections
- Pancreatic insufficiency **
- Steatorrhea
- Malnutrition
- Hepatic cirrhosis
- Intestinal obstruction
- Male infertility
- Bronchiectasis
CF:
The most common mutation in the ? gene results in defective protein folding in the Golgi/endoplasmic reticulum and degradation of ? before it reaches the cell surface.
CFTR
The pathogenesis of respiratory and intestinal complications in cystic fibrosis seems to stem from an isotonic but low-volume surface fluid layer.
- In the lungs, this dehydration leads to defective mucociliary action and the accumulation of hyperconcentrated, viscid secretions that obstruct the air passages and predispose to ?
Recurrent pulmonary infections
CF:
Pancreatic insufficiency causes ?
- Impaired fat absorption
- Vit A deficiency (squamous metaplasia)
- Meconium ileus (small bowel obstruction)
CF:
Three most common organisms responsible for lung infections?
Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa
Clinical features of CF?
- Can appear at birth - meconium ileus in 5-10%
- Intussusception
• Years later (table 10-5) –
- Exocrine pancreatic insufficiency
- Cardiorespiratory – recurrent nasal polyps 10-25%
- Liver disease – puberty
- Infertility –> obstructive azoospermia
How to diagnose CF?
characteristic clinical findings, sweat chloride test, IRT, CFTR sequencing
Defined as “the sudden death of an infant under 1 year of age which remains unexplained
after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history.
SIDS
Many cases of sudden death in infancy may have an unexpected anatomic or biochemical basis discernible at autopsy
SUID (sudden unexpected infant death)
- SIDS is the leading cause of death between age ?
- The ? leading cause of death overall in infancy, after congenital anomalies and diseases of prematurity and low birth weight
- 1 month and 1 year (90% occur in first 6 months of
life) in this country - Third
Morphological findings of SIDS?
- Petechiae on Lungs, Thymus, and Heart
- Congested lungs and vascular engorgement with or without pulmonary edema
Some Risk Factors for SIDS (table 10-6)
- Parental = ?
- Infant = ?
- Environment = ?
- Parental
- Young maternal age (less than 20 years)
- Smoking
- Drug use in either parent
- Short intergestational intervals
- Late or no prenatal care
- Low socioeconomic group
- AA or American Indian - Infant
- Brain stem abnormalities associated with delayed development of arousal and cardiorespiratory control *
- Premature and low birth weight
- Male sex
- Product of a multiple birth
- SIDS in a prior sibling
- Antecedent Respiratory infections
- Germline polymorphisms - Environment
- Prone or side sleep position
- Sleeping on a soft surface
- Hyperthermia
- Co-sleeping in first 3 months of life
Benign Tumors:
normal cells in abnormal location
Heterotopia (choristoma)
Benign Tumor:
excessive focal overgrowth of tissue native to the organ
Hamartoma
The most common tumor of infancy
- Examples?
Hemangioma
- Ex. Capillary hemangioma; Port wine stain
(Benign tumor)
What kind of benign tumor are lymphangioma and lymphangiectasia?
lymphatic tumors
What kind of benign tumors can look like adult type fibrosarcoma in adults but do better?
Fibrous tumors
What kind of benign tumor are 2 peaks of age, more histologically mature = better prognosis
Teratoma
Most common teratoma
- F>M, 4:1
Sacrococcygeal teratoma
Common Malignant Neoplasms of Infancy and Childhood:
- Leukemia involves what age groups?
- 0 to 4 years
- 5 to 9 years
Common Malignant Neoplasms of Infancy and Childhood:
- Retinoblastoma involves what age groups?
- 0 to 4 Years
- 5 to 9 Years
- *Common Malignant Neoplasms of Infancy and Childhood:
- Neuroblastoma involves what age groups?
- 0 to 4 years
- 5 to 9 years
- **Common Malignant Neoplasms of Infancy and Childhood:
- Wilms tumor involves what age groups?
- 0 to 4 Years
Common Malignant Neoplasms of Infancy and Childhood:
- Hepatoblastoma age group?
- Hepatocellular carcinoma age group?
- Hepatoblastoma = 0 to 4 years
- Hepatocellular carcinoma = 5 to 9 years; 10 to 14 Years
Common Malignant Neoplasms of Infancy and Childhood:
- Soft tissue sarcoma (esp rhabdomyosarcoma) ages?
- Soft tissue sarcoma ages?
- Soft tissue sarcoma (esp rhabdomyosarcoma) = 0 to 4 Years
- Soft tissue sarcoma = 5 to 9 Years; 10 to 14 years
Common Malignant Neoplasms of Infancy and Childhood:
- Teratoma age group?
0 to 4 years
Common Malignant Neoplasms of Infancy and Childhood: Age Groups of: - CNS tumors? - Ewing sarcoma? - Lymphoma? - Osteogenic sarcoma? - Thyroid carcinoma? - Hodgkin disease ?
- CNS tumors = 0 to 4 years; 5 to 9 Years
- Ewing sarcoma = 5 to 9 years
- Lymphoma = 5 to 9 years
- Osteogenic sarcoma = 10 to 14 Years
- Thyroid carcinoma = 10 to 14 years
- Hodgkin disease = 10 to 14 years
Only 2% of all malignant tumors occur in infancy and childhood; nonetheless, cancer (including leukemia) accounts for about ?% of deaths in the United States in children older than age 4 and up to age 14 years, and only ? cause significantly more deaths.
- 9%
- accidents
Histologically, many of the malignant non-hematopoietic pediatric neoplasms are unique.
- Tend to have a more primitive (embryonal) ? appearance, are often characterized by sheets of cells with small, ? nuclei, and frequently show features of organogenesis specific to the site of tumor origin. Because of this latter characteristic, these tumors are frequently designated by the suffix - ?
- Because of their primitive histological appearance many childhood tumors are collectively called ?
- UNDIFFERENTIATED
- ROUND
- blastoma
- small round blue cell tumors
There is a tendency of fetal and neonatal malignancies to regress or differentiate ?
Spontaneously
? survival or cure of many childhood tumors, so that more attention is now being devoted to minimizing the adverse delayed efforts of chemotherapy and radiation therapy in survivors, including the development of second malignancies
Improved
Most common EXTRACRANIAL SOLID TUMOR OF CHILDHOOD,
and the most frequently diagnosed tumor of infancy
Neuroblastoma
Neuroblastoma Prevalence:
- approximately ? cases diagnosed each year in the United States
700
Neuroblastoma:
- Median age at diagnosis is ?; approximately ?% of cases are diagnosed in
infancy
- 18 months
- 40%
most neuroblastomas occur sporadically, but ?% to ?% are familial (ALK gene =
anaplastic lymphoma kinase)
1% to 2%
Morphological features of Neuroblastoma
- In childhood, about 40% arise in the adrenal medulla
- Histo = Neuropil; Homer-Wright pseudorosette
- GANGLIONEUROMAS, arising from spontaneous or therapy-induced maturation of neuroblastomas, are characterized by clusters of large cells with vesicular nuclei and abundant eosinophilic cytoplasm, representing neoplastic ganglion cells. Spindle-shaped Schwann cells are present in the background stroma.
Clinical Features of Neuroblastoma?
- > 2 y.o. may present with mets (blood and lymphatic)
- periorbital region a common metastatic site
- <2 y.o. with large abdominal mass, fever, +/- weight loss
- Infants with multiple cutaneous mets “blueberry muffin baby”
Important diagnostic feature of neuroblastoma?
Catecholamines (i.e., elevated blood levels of catecholamines and elevated urine levels of the metabolites vanillylmandelic acid [VMA] and homovanillic acid [HVA])
Neuroblastoma Prognostic Factors:
Stage:
1. Favorable = ?
2. Unfavorable = ?
- Favorable = Stage 1, 2A, 2B, 4S
2. Unfavorable = Stage 3, 4
Neuroblastoma Prognostic Factors:
Age:
1. Favorable = ?
2. Unfavorable = ?
- Favorable = <18 months
2. Unfavorable = >18 months
Neuroblastoma Prognostic Factors: Histology: A.) Evidence of schwannian stroma and gangliocytic differentiation 1. Favorable =? 2. Unfavorable = ?
B) Mitosis-karyorrhexis index
- Favorable = ?
- Unfavorable = ?
A) Evidence of schwannian storm and gangliocytic differentiation
- Favorable = Present
- Unfavorable = Absent
B) Mitosis-karyorrhexis index
- Favorable = <200/5000 cells
- Unfavorable = >200/5000 cells
Neuroblastoma Prognostic Factors:
DNA ploidy:
1. Favorable = ?
2. Unfavorable = ?
- Favorable = Hyperdiploid (whole chromosomal gains)
2. Unfavorable = Near-diploid (Segmental chromosomal losses; chromothripsis)
Neuroblastoma Prognostic Factors:
MYCN:
1. Favorable = ?
2. Unfavorable = ?
- Favorable = Not amplified
2. Unfavorable = Amplified
- ? uses DNA probes that recognize sequences specific to particular chromosomal regions.
- Gene amplification (i.e. ? amplification in neuroblastomas).
- FISH
- NMYC
Unfortunately, most (60% to 80%) children present with stage ? tumors, and only 20% to 40% present with stage ? neuroblastomas. The staging system is of paramount importance in determining prognosis.
- 3 or 4
- 1, 2A, 2B, or 4S
One peculiar form of segmental aberration described recently in aggressive neuroblastomas is called?
- Characterized by extensive ? and an oscillating pattern of DNA copy number levels, all curiously restricted to one or a few chromosomes.
chromothripsis
- genomic rearrangements
Prevalence of Wilms Tumor:
Afflicts about 1 in every ?children in the US , making it the most common ? tumor of childhood and the ? most common pediatric malignancy in the US
- 10,000
- renal
- fourth
Many children with Wilms tumor present with?
- Large abdominal mass (either unilateral or when large can extend into the pelvis) ***
- Hematuria
- Pain in the abdomen after some traumatic incident
- Intestinal obstruction
- Hypertension
- Pulmonary metastases
Morphology of Wilms Tumor
- 5% show ANAPLASIA = ? mutation
• Large solitary well circumscribed mass although are either 10% bilateral or multicentric
- The cut surface is soft, homogeneous, tan-grey
- Can have necrosis, cysts formation or hemorrhage
•Classic triphasic combination of blastemal, stromal, and epithelial cell types is observed in the vast majority of lesions
- Blastemal = small blue cells
- Epithelial = tubules
- Stromal = fibrocytic or myxoid
• 5% show ANAPLASIA = TP53 mutation
- Lack of differentiation, or anaplasia, is considered a
hallmark of malignancy (pleomorphism, abnormal
nuclear morphology, mitoses, loss of polarity)
• Can have heterologous elements
The risk of Wilms tumor is increased with at least 3 recognizable groups of congenital malformations associated with distinct chromosomal loci
- ?
- ?
- ?
- WAGR/WAGI syndrome
- Denys-Drash syndrome
- Beckwith-Wiedeman syndrome
Wilms Tumor: WAGR syndrome (33% risk)
- What does WAGR stand for?
- Germline deletion of ?
- ? = Wilms tumor-associated gene
- ? = provides instructions for making a protein that is involved in the early development of the eyes, brain, spinal cord and pancreas
- Germline ? deletion is first hit, second hit is frameshift or nonsense mutation in second allele
- Wilms tumor, Aniridia, Genital anomalies, mental Retardation
- 11p13
- WT1
- PAX6
- WT1
Wilms Tumor: Denys-Drash syndrome (90% risk)
• Gonadal dysgenesis (male ?)
• Early onset nephropathy
–> ?
• Increased risk of ?
- pseudohermaphrodism
- renal failure
- gonadoblastoma
Wilms Tumor: Beckwith-Wiedemann syndrome
- Clinical features?
- Example of ? - 11p15.5 (WT2 – IGF2)
- Some have ? mutation - a cell cycle regulator (p57) that broadly inhibits
multiple CDKs - Increased risk of ?
- Organomegaly, macroglossia, hemihypertrophy, omphalocele, adrenal cytomegaly
- genomic imprinting
- CDKN1C
- hepatoblastoma, pancreatoblastoma, adrenal cortical tumors, rhabdomyosarcoma
Wilms Tumor
- Putative precursor lesions of Wilms tumors and are seen in the renal parenchyma and adjacent to approximately 25% to 40% of unilateral tumors; this frequently rises to 100% in cases of bilateral Wilms tumor = ?
- It is important to document the presence of these in the resected specimen, because these patients are at an increased risk of developing Wilms tumors in the ? kidney and require regular and frequent surveillance for many years
NEPHROGENIC RESTS
- contralateral
The time lag between the first and second malignant transformation is variable. Two or more primary carcinomas can coexist at the time of diagnosis (?), or develop consequently (?), sometimes years after resection of the first primary.
- synchronous
- metachronous
Clinical features of Fetal Alcohol Syndrome Disorder
- prenatal and postnatal growth retardation
- facial anomalies (microcephaly, short palpebral fissures, maxillary hypoplasia)
- psychomotor disturbances
