Sie sind auf Seite 1von 76

Genetic and Pediatric Diseases

All diseases involve some changes in gene structure or expression - Robbins Basic Pathology



Genetic Diseases
Definition: Definition: y A pathological condition caused by an absent or defective gene or by a chromosomal aberration is termed as a genetic disorder. y Humans have 30,000 genes that can involve in changes to their structure, causing diseases. Hereditary disorders diseases derived from parents y Familial disorders diseases transmitted in gametes through generations y Congenital disorders diseases present at birth. y Note: Some congenital diseases are not genetic and not all genetic diseases are congenital

The Gene

Mutation implies permanent changes in the DNA; y Mutations affecting germ cells transmitted to progeny; mutations affecting somatic cells not transmitted but causes cancers or malformations

Common types of gene mutations: y Point mutations (missense mutations) substitution of a single nucleotide base resulting in replacement of single amino acid in protein molecule. e.g. sickle cell anemia

Frameshift mutation insertion or deletion of one or two base pairs; changes DNA reading frame e.g. Tay-Sachs disease Trinucleotide repeat mutations amplification of 3 sequential nucleotides e.g. Fragile X syndrome 4

To understand it easier, let us view genes as sentences and their mutations as typo errors in the sentences Sample gene: e.g. "The fat cat ate the wee rat" Point Mutation: changing one letter in the sentence/(gene)
Original: The fat cat ate the wee rat. Point Mutation: The fat hat ate the wee rat.

Frame-shift mutation: adding or removing letters in a sentence/(gene)

Original: The fat cat ate the wee rat. Frame Shift: The fat caa tet hew eer at.

Deletion: removal of just one word," or longer deletions

Original: The fat cat ate the wee rat. Deletion:The fat ate the wee rat.

Insertion: addition of extra word or extra DNA

- Original: The fat cat ate the wee rat. - Insertion:The fat cat xlw ate the wee rat.

Categories of Genetic Disorders

Disorders occur due to: 1) Mutant genes of large effect Mendelian disorders e.g. storage diseases; from single gene mutations. They are hereditary and familial. Multifactorial inheritance due to both genetic and environmental influences e.g. hypertension, diabetes mellitus Chromosomal aberrations due to numeric or structural aberrations. e.g. Downs syndrome, Turners syndrome, Jacobsen syndrome



Single gene disorders with nonclassic inheritance - Due to mutations in mitochondrial DNA, genomic imprinting, or due to triplet repeat mutations. e.g. Angelman syndrome

Father of Genetics

Gregor Johann Mendel (1822 1884)


Mendelian Disorders
(Single(Single-Gene Defect)
Follows Mendelian pattern of inheritance. Three patterns: 1) Autosomal Dominant disorders 2) Autosomal Recessive disorders 3) X-linked disorders Autosomal Dominant: Dominant Manifests in heterozygous states; mutation of one allele At least one parent is affected, males/female; both can transmit Enzyme proteins not affected but receptors and structural proteins are involved; onset late sometimes e.g. Marfans syndrome, Achondroplasia, Huntingtons disease If an affected person marries an unaffected individual, every child has 50% chance of inheriting the disorder

Autosomal Recessive: Recessive Largest group; both copies (alleles) are mutated; a) Parents asymptomatic (trait); but children show disease b) Siblings have 1 in 4 chance of being affected (25% risk) c) Possibility more in consanguineous marriage d) Males and females equally affected; early onset e) It involves enzyme proteins. e.g. Cystic Fibrosis, Wilsons disease, Sickle cell anemia X-linked linked: Sex-linked disorders; all are X-linked ; no Ys yet  most are recessive  transmitted by heterozygous females to their sons,  affected males do not transmit to sons but daughters become carriers e.g. Hemophilia, Duchenne muscular dystrophy

Some Mendelian Disorders

y y y y y y y y y

Adult polycystic kidney disease Familial hypercholestrolemia Hereditary hemorrhagic telangiectesia (Osler- WeberRendu syndrome) Hereditary spherocytosis Huntingtons disease Marfans syndrome Neurofibromatosis (von Recklinghausens disease) Tuberous sclerosis Von Hippel- Lindau disease

Mutations of structural proteins

Marfan Syndrome
Autosomal dominant disorder of connective tissue affecting fibrillin, found in ECM, a glycoprotein secreted by fibroblasts; prevalence 1 in 20,000; 75% familial Deficiency of fibrillin can production of cytokine TGF(transforming growth factor) Clinical manifestations are seen mainly in: *Skeleton long legs, arms, fingers (arachnodactyly); high arched palate, kyphoscoliosis, pectus excavatum or pigeon chest deformity, hyperextensible joints *Eyes subluxation of lens *Cardiovascular Aneurysms, aortic dissection, aortic incompetence, mitral valve prolapse, congestive cardiac failure; death can occur due to aortic rupture


Marfan Syndrome


EhlersEhlers- Danlos Syndromes (EDSs)

Single gene disorder but can show all 3 Mendelian patterns y Characterized by defects in collagen synthesis or structure; six variants of the disease are presented y Skin, ligaments and joints affected Clinical Features: y Extraordinarily stretchable and fragile skin vulnerable to trauma Produce gaping wounds, show poor wound healing y Hypermobile joints y Internal complications like rupture of colon or large arteries, diaphragmatic hernias, rupture of cornea and retinal detachments due to collagen deficiency 13

Ehlers-Danlos Syndromes


Mutations of receptor proteins

Familial Hypercholesterolemia
y y y

y y

Most common mendelian disorder; 1 in 500 Autosomal dominant disorder; mutations in genes for LDL receptor Results in impairment of intracellular LDL transport and catabolism; in addition, there is excessive synthesis of LDL; this leads to hypercholesterolemia; best treated by statins Hypercholesterolemia leads to premature atherosclerosis and xanthomas Heterozygotes are symptomless until adulthood; only show elevated serum cholesterol, es risk for atherosclerosis, CAD Homozygotes greater risk, die by age 15 due to MI

Mutations of enzyme proteins

Phenylketonuria (PKU)
y Common in Caucasians and esp. Scandinavians y Autosomal recessive disorder y Show inability to convert phenylalanine to tyrosine due to

lack of phenylalanine hydroxylase y Clinical features severe mental retardation inability to walk or talk, suffer from seizures hypopigmentation of hair and skin (musty odor); eczema y Avoided by restriction of phenylalanine in diet during early life y Clinically normal pregnant females with unrestricted diet give birth to mentally retarded children (maternal PKU); also increases risk of spontaneous abortion 16

Avoid high protein foods, such as milk, dairy products, meat, fish, chicken, eggs, beans, and nuts


y y y y

Autosomal recessive; affects 1 in 30,000 Show inability to convert galactose to glucose due to lack of a transferase enzyme Clinical features: Mainly affects liver, brain, eye Infancy Develop vomiting, diarrhea from birth; fail to thrive; jaundice and hepatomegaly (fatty liver) after 1 week; later aminoaciduria, chances of E.coli sepsis Older children/adults (without appropriate therapy) cataract, speech defects, neurological deficits, cirrhosis liver, ovarian failure Clinical and morphological changes prevented by early avoidance of galactose in diet for first 2 years of life


Lysosome Storage Diseases

y y

y y y

Due to lack of lysosomal enzymes Resultant accumulation of substances like, sphingolipids and mucopolysaccharides within lysosomes as a result of ingestion by phagocytosis Autosomal recessive; 40 lysosomal storage diseases present, each lacking specific lysosomal enzymes Affects infants and young children Show hepatosplenomegaly, cellular dysfunctions (due to macrophage activation, cytokines release), CNS neuronal damage


Lysosome Storage Diseases

TayTay-Sachs Disease (gangliosidosis)

Inability to metabolize GM2 gangliosides due to deficiency of hexosaminidase A, a lysosomal enzyme y Common among Ashkenazi Jews y Causes accumulations in brain cells; affected cells appear swollen & foamy, with whorled lysosomes; also seen in spinal cord, peripheral nerves y Infants appear normal at birth with motor weakness beginning at 3-6 months of age mental retardation, blindness, neurological dysfunction; death follows within 2-3 yrs.

Lysosome Storage Diseases

NiemannNiemann-Pick Disease: Types A & B

Caused by deficiency of sphingomyelinase enzyme, accumulation of sphingomyelin in phagocytes and nerve cells Affected organs are spleen, liver, bone marrow, lymph nodes and lungs; leads to visceromegaly, neurological dysfunction and death by 3 years of age Type B has organomegaly but no neuronal damage Type C: (NPC) More common than A or B, defect in cholesterol transport; resulting in accumulations of cholesterol and gangliosides Affected children have ataxia, gaze palsy, dystonia, dysarthria, and psychomotor regression


Lysosome Storage Diseases

Gaucher Disease

Accumulation of glucosylceramide in phagocytes due to lack of enzyme glucosylceramidase

Phagocytes transform to Gaucher cells in liver, spleen, bone marrow, and lymph nodes y Hepatosplenomegaly, bone erosion result Type 1 no neurological involvement, have long life; common in Ashkenazi Jews Type II, Type III neurological involvement dominant,Type II severe (short life span), Type III is milder Treatment Enzyme replacement by infusing purified enzyme, drugs, gene therapy

Lysosome Storage Diseases

Gaucher Disease

A typical Gaucher cell (a lipid laden macrophage) in the bone marrow.

The 14-year old girl in this photo has Gaucher Disease (GD).


Lysosome Storage Diseases

Due to defective degradation and accumulation of mucopolysaccharides within lysosomes in liver, spleen, heart, blood vessels, brain, cornea, joints. [Mucopolysaccharides (dermatan sulphate, chondroitin sulphate) form part of ECM] Patients have course facial features, corneal clouding, joint stiffness and mental retardation Type I or Hurlers syndrome severe, death in childhood (6-10 yrs) due to cardiovascular complications Type II or Hunter syndrome milder course, X-linked; absence of corneal clouding

Lysosome Storage Diseases

Mucopolysacccharidoses Type 1

Photograph showing coarse facies, corneal clouding and large mouth.


Glycogen Storage Diseases

Accumulation of glycogen due to deficiency of enzyme in glycogen synthesis or degradation 1. Hepatic type - Results in hepatomegaly and hypoglycemia e.g. von Gierke disease, most important, due to glucose-6-phosphatase deficiency, 2. Myopathic type Muscle weakness, cramps, myoglobinuria, failure to induce ed lactic acid after exercise (Type V McArdle disease) 3. Type II Pompe disease (variant - is a form of lysosomal storage disease), deposition of glycogen in every organ, cardiomegaly prominent Type IV Brancher glycogenosis (in liver, heart and muscles)

von Gierke disease

Pompe disease

Liver with a pale, bulging surface, filled with glycogen in von Gierke's disease due to lack of glucose-6phosphatase enzyme

This is the heart of a 9 month old child who died of congestive failure. The ventricular walls are enormously thickened.

Cytogenetic Disorders
One in 200 newborn infants show some alterations in number or structure of chromosomes

Numeric Abnormalities
y y

y y y y

May affect autosomes or sex chromosomes. The normal chromosomal count is 46, that is 2n=46; 23 (nhaploid number) from each parent (22 autosomes and 1 sex chromosome). Euploid exact multiple of haploid number (2n) Polypoid increasing multiples, i.e. 3n or 4n; results in spontaneous abortion Aneuploid not an exact multiple of n Gametes then have an extra chromosome (n+1) or one less (n-1); Fertilization of such gametes by normal gametes result in 2n+1 (Trisomy) or 2n-1(monosomy)

Structural Abnormalities
These result from chromosomal breakage followed by loss or rearrangement of material. The different loss/ rearrangements are: y Translocation y Isochromosomes y Deletion y Inversions y Ring chromosomes Chromosomes:  Described as having short arm (p=petit) and long arm (q)  Each arm then divided into numbered regions (1,2,3.) from the centromere outward  Each region has bands that are numerically arranged  Thus 2q34 = chromosome 2, long arm, region 3, band 4

Is the exchange of chromosomal segments between non-homologous chromosomes. y Denoted by t y E.g. Downs syndrome, t (14q:21q)

A transverse rather than a longitudinal division occurs. One arm is lost and the remaining one duplicates Results in new chromosome with two short arms or two long arms



y y y y

Is most often absence of a portion of a chromosome, although it can be loss of an entire chromosome. Denoted by - (minus) p- short arm q- long arm E.g. cri du chat 46XY, 5p-

Is reunion of a chromosome at two points, in which the internal fragment is reinserted in an inverted position.


Sex Chromosomes
y y

y y y y

Extreme karyotype deviations in sex chromosomes are compatible with life This is believed to be due to the Lyonization (inactivation) of X chromosome and scant genetic information carried by the Y chromosomes. All but one X chromosome is inactivated and so a 48, XXXX female has only one active X chromosome The inactive X, forms a discrete body within the nucleus called a Barr body (Sex chromatin) Normal females (XX) will have one Barr body Normal males (XY) or (XO) individuals will have no Barr bodies.

In summary
Chromosomal disorders occur: y Due to absence (deletion, monosomy), excess (trisomy),or abnormal arrangements (translocations) of chromosomes y Loss effects more severe defects than gain y Sex chromosome abnormalities are better tolerated than autosome abnormalities y Sex chromosome disorders are subtle and sometimes are not detected at birth e.g. infertility y Usually chromosomal disorders are the result of de novo changes. Hence if parents are normal, risk of recurrence in siblings is low; exception Down syndrome

Disorders of autosomes

Trisomy 21 (Down Syndrome)

Causes- Meiotic non-disjunction of chromosome 21, results in extra chromosome count (47; 2n+1) y Mostly, parents are normal; Incidence increases with maternal age y In a few (familial form), translocation occurs from chromosome 21 to chromosome 22 or 14 (no extra) y Is marked by: Severe mental retardation Large forehead, broad nasal bridge, wide-spaces eyes, epicanthal folds, large protruding tongue Brushfields spots (white spots on the iris) Short, broad hands with curvature of the fifth finger Simian crease, a single palmar crease Unusually wide space between 1st and 2nd toes

Downs Syndrome


Hand - features short and broad hands, Clinodactyly (curving), with a single flexion crease (20%) of little finger, and hyperextensible finger joints. Foot - space between great toe (big) and second toe is increased. Hip - acquired hip dislocation (6%).


y y y y y y

Congenital heart disease (40%),VSD Acute leukemia (20x) ALL Increased susceptibility to infection Median age at death 47 years; usually due to cardiac or infectious causes Patients surviving to middle age, proceed to Alzheimers disease Many develop frank dementia


There is an abnormal transverse crease across the palm of each hand seen here.Together with the single flexion crease on the 5th digit, this is quite typical for trisomy 21 (e.g., 47, XX, +21).

Edwards syndrome
y y

Results from nondisjunction resulting in trisomy 18 Mental retardation, prominent occiput, microganthia, low set ears, short neck, rockerbottom feet, flexion deformities of the fingers and congenital heart disease.


Pataus syndrome (trisomy 13) (trisomy


Is manifested by mental retardation, microcephaly, micropthalmia, brain abnormalities, cleft lip and palate, polydactyly, rocker-bottom feet, umbilical hernia, renal defects and congenital heart disease.



Cri du chat (cry of a cat) (Le Jeunes syndrome)

Is caused by deletion of the short arm of chromosome 5 (5p-) y Sever mental retardation, microcephaly and unusual catlike cry. y LBW, round face, hypertelorism, low set ears and epicanthal folds.


Abnormalities of sex chromosomes

Klinefelters syndrome
y y y y y y

Male hypogonadism, with 2 X and 1 or more Y chromosomes e.g. 47, XXY Single Barr body on buccal smear Advanced maternal age or irradiation of either parents may be contributing factors Features: Atrophic testis, tall stature, an eunuchoid appearance with gynecomastia, mental retardation (mild) Decreased testosterone production and increased pituitary gonadotropins. Have associated disorders like cancers (breast) or autoimmune diseases (SLE)

Turners syndrome (45, X) (45, X)

y y y y y y y

y y

Hypogonadism in females; Is most common cause of primary amenorrhea. No Barr body Not complicated by mental retardation Ovaries are replaced by fibrous streaks Decreased estrogen production and increased pituitary gonadotropins Infantile genitalia and poor breast development Short stature, webbed neck, shield like chest with widely spaced nipples, high-arched palate, and a wide carrying angle of the arms (cubitus valgus). Bicuspid aortic valve, coarctation of aorta, horse-shoe kidney Lymphadema of extremities, cystic hygroma 44

Klinefelters Syndrome

Turners Syndrome


Single gene disorders with nonclassic inheritance TripletTriplet-Repeat Mutations

Fragile X syndrome
y y y

y y

Is an important cause of familial mental retardation second in frequency only to Down syndrome. Defect on long arm of chromosome X repeating sequences of 3 nucleotides Usually affects males (but 20% of males are only carriers; can develop neurodegenerative syndrome); females are usually carriers (but 50% have mental retardation, 30% ovarian failure) Mental retardation, long face, large mandible, and large everted ears, bilateral macro-orchidism Results from mutation of FMR1 gene

Fragile X syndrome


Genomic Imprinting
Usually homologous genes from both parents are functionally identical Functional differences are seen sometimes, arising from epigenetic process and this is called genomic imprinting. Some genes are silenced/inactivated during this process Imprinting first occurs in ovum and sperm and then transmitted to all somatic cells; best seen in: Prader-Willi Syndrome: y Mental retardation, short stature, hypotonia, obesity, small hands and feet, hypogonadism. y Deletion of band q12 in long arm of chromosome 15 from the father. Angelman Syndrome: y Deletion of same chromosomal region from mother. Ataxia, seizures, inappropriate laughter in addition to mental retardation. 48 Happy puppet Syndrome.

Pediatric Diseases

Infancy: Covers first year of life highest risk of mortality Neonatal period: Covers first 4 weeks of life - most dangerous and susceptible period

Congenital anomalies: Structural defects present at birth; Extrinsic or Intrinsic Malformations intrinsic abnormal development; usually multifactorial e.g. cleft lip, cleft palate, polydactyly Disruptions due to extrinsic disturbance in development, not heritable, no recurrence risks e.g. Amniotic bands, Thalidomide baby, diabetic embryopathy Deformations extrinsic disturbance, usually abnormal biomechanical forces e.g. uterine constraints like small uterus, multiple fetuses, abnormal presentations Sequence multiple anomalies from secondary effects of a single local aberration e.g. Potter sequence 50 Malformation syndromes from a single causative



Thalidomide Baby

Potter sequence


Disruptions - Amniotic band syndrome






Malformations - Cleft lip and palate


Causes of Pediatric Diseases

Genetic: Chromosomal anomalies e.g. Downs, Turners, Klinefelters syndromes Environmental: Influences like e.g. Rubella embryopathy, fetal alcohol syndrome, diabetic embryopathy, drugs -thalidomide, anticonvulsants, warfarin Multifactorial: Interaction of environmental influences with two or more genes e.g. cleft lip and palate, neural tube defects

Timing of prenatal insult has profound impact.

First 3 weeks after fertilization death and abortion or recovery without damage Between 3 -9 weeks susceptible to teratogenesis Peak sensitivity between 4th and 5th weeks. After 9 weeks susceptible to growth retardation and injury to formed organs

Perinatal Infections
Transcervical : Ascending infections from vagina; acquired in utero or during birth e.g. bacterial and viral infections. Fetus acquires infection by inhaling infected amniotic fluid into lungs. e.g. pneumonia, sepsis, meningitis Transplacental: Hematologic, by crossing the placenta, occurs during gestation or at the time of delivery. e.g. parasitic, viral infections, hepatitis B, HIV TORCH Infections: Herpes (H); Toxoplasma(T); Others (O) Rubella (R); CMV (C);

Gestational age less than 37 weeks y Infants weigh less than normal (<2500gm) y Risk factors: Premature rupture of membrane Intrauterine infection Structural abnormalities of uterus & placenta Multiple fetuses y Complications in preterm infants: Hyaline membrane disease (ARDS) Necrotizing enterocolitis Intraventricular and germinal matrix hemorrhage Patent ductus arteriosus


Respiratory Distress Syndrome (RDS)


y y y y y

Contributory factors of respiratory distress x excessive sedation of mother x fetal head injury, aspiration x cord around the neck x diabetic mother x cesarean section before onset of labor x twin gestation x hyaline membrane disease (RDS) RDS is usually a disease of premature infants Occurs in 60% of infants born preterm (<28wks) Fundamental defect inability to synthesize enough surfactant by immature lung. Alveoli tend to collapse, atelectasis sets in. Treatment: Corticosteroids, surfactant therapy


Role of Surfactant

=Surface active agent in water Secreted by some alveolar epithelial cells (type II pneumocytes) pneumocytes) Similar to soap Lowers surface tension Made of phospholipids, proteins, and ions Phospholipid dipalmitoylphosphatidylcholine It reduces the surface tension, thus decreasing the pressure to keep the alveoli open. Lack of it leads to atelectasis.


Necrotizing Enterocolitis
y y y

y y y

Occurs in premature infants (birth weight <1500gm); high mortality Predisposing factors hypoperfusion, bacterial colonization, formula feeds Intestine distended, friable, congested or gangrenous, ulcerations (leading to perforations and peritonits), gas bubbles Symptoms bloody stools, distension, circulatory collapse; radiograph shows gas in intestines Treatment conservative or surgical Complications strictures after healing

Necrotizing Enterocolitis
The plain abdominal film shows air in the portal vein, air in the bowel walls, and a large pneumoperitoneum [subdiaphragmatic free air, perihepatic free air, double wall sign (blue arrows), triangle sign (green arrows), and falciform ligament (red arrow)].


Sudden Infant Death Syndrome (SIDS)

Death under 1 year of age with unexplained cause; usually between 2-4 months of age y Usually occurs in sleep, hence called crib death or cot death y Delayed development of arousal and cardiorespiratory control, the best hypothesis; hence low response to stimuli like hypercarbia, hypoxia, thermal stress Potential environmental causes prone sleeping position, soft bedding Morphology: Petechiae on thymus, pleura and epicardium


Fetal Hydrops
Refers to accumulation of edema fluid in fetus Immune Hydrops: y Antibody-induced hemolytic disease in newborn due to ABO or Rh (D) incompatibilty between mother and fetus. y Due to seepage of fetus RBCs into maternal circulation during last trimester causing antibodies to develop in mother. These antibodies can traverse placenta initiating hemolysis in fetus . Rh hemolytic disease is uncommon in first pregnancy. y Results in progressive anemia, cardiac failure, edema; The severe anemia (Erythroblastosis fetalis) is treated by exchange transfusion y Prevented by anti-D globulin shots to mothers

Nonimmune Hydrops Associated with cardiovascular defects, chromosomal anomalies and fetal anemia resulting in intrauterine cardiac failure and hydrops. e.g in Turners syndrome, mucopolysaccarridosis type VII, Parvovirus infection, thalassemia, cystic hygroma ________________________________________ Diagnosis by testing Rh antibody titers in mother (rising titer diagnostic) Positive Coombs test in fetal cord blood Management: Antenatal exchange transfusion, anti-D globulins to mother can prevent immune hydrops in subsequent pregnancies; postnatal phototherapy for associated jaundice

Immune hydrops

Fetal Hydrops

Erythroblastosis Fetalis

Cystic Fibrosis
Most common lethal genetic disease of Caucasians; uncommon among Asians and African Americans; autosomal recessive Widespread epithelial disorder affecting fluid transport in exocrine glands, in GI, respiratory and reproductive tracts Results in increased viscosity of mucous and increased sodium and chloride concentrations in sweat and tears. Leads to recurrent lung infections and pancreatic insufficiency


Cystic Fibrosis


Clinical manifestations: Chronic pulmonary disease Pancreatic insufficiency Meconium ileus Liver involvement steatosis, cirrhosis In males azoospermia, infertilty with bilateral absence of vas deferens Clinical symptoms: y Malabsorption symptoms large, foul stools, abdominal distension, persistent diarrhea, poor weight gain, avitaminosis A,D,K y Cardiorespiratory chronic cough, persistent lung infections, COPD, Cor pulmonale

Pediatric Tumors
Benign Tumors: Hemangiomas most common, in the skin (face, scalp) e.g. port-wine stains May spontaneously regress or enlarge; merely of cosmetic significance Lymphangiomas characterized by cystic or cavernous spaces containing pale fluid, surrounded by lymphoid aggregates; occur on skin or deeper regions of neck, axilla, mediastinum, and retroperitoneum Sacrococcygeal teratomas: Most common germ cell teratomas tumor; benign but 12% turn malignant


PortPort-wine stains

Sacrococcygeal teratoma


Malignant Tumors
Neuroblastoma: Tumors of the sympathetic ganglia and adrenal medulla. They demonstrate spontaneous regression and spontaneous/or therapy-induced maturation Prognosis depends on staging of tumor (4S being excellent) and age (children below 1 year of age better outlook) Present with fever, weight loss, protuberant abdomen (ascitis), hepatomegaly, bone pain. Can metastasize to liver, lungs, and bone marrow, skin (blueberry muffin baby) Secrete catecholamines; its metabolites (VMA, HVA) are used for screening

Blueberry muffin baby

Neuroblastoma. This tumor is composed of small cells embedded in a finely fibrillar matrix (neuropil). A Homer-Wright pseudorosette (tumor cells arranged concentrically around a central core of neuropil) is seen in the upper right corner.


y y y y y y y

Most common malignant eye tumor of childhood, congenital, multifocal, bilateral Undergoes spontaneous regression Occur as familial and sporadic patterns Familial retinoblastoma have increased risk for developing osteosarcoma May metastasize to CNS, skull, bones, and lymph nodes Patients have poor vision, strabismus, whitish blue pupil (cats eye reflex), eye pain Treatment: Enucleation, chemo & radiotherapy

cats eye reflex

Retinoblastoma. A, Note poorly cohesive tumor in retina abutting optic nerve. B, Higher power view showing FlexnerWintersteiner rosettes (arrows) and numerous mitotic figures


Wilms Tumor
Known as nephroblastoma, occurs in children between 2 and 5 years y Three congenital malformations are associated with risk of developing Wilms tumor a) WAGR Syndrome (33% chance) b) Denys-Drash Syndrome (DDS) (~90% chance) c) Beckwith Wiedemann Syndrome (BWS) y Presents as large, solitary, well-circumscribed mass Symptoms: Abdominal pain, fever, hematuria or intestinal obstruction Prognosis: Excellent with surgery and chemo Diffuse anaplasia, with extra-renal spread has bad prognosis

Wilms Tumor