Flashcards in Chapter 6: Genetic and Pediatric Diseases Deck (99):
How many genes are in the human genome?
25,000 protein-coding genes
This is an organism's genetic material.
This is a discrete set of nucleotides. It is a section of DNA that instructs protein synthesis and is a unit of inheritance.
This is a single genetic locus and an alternative form of a gene.
These are permanent changes in DNA.
-Germ line (hereditary): all cells
-Somatic (acquired): some cells
This term refers to conditions transmitted to offspring.
This term refers to all of the last trimester and one month after.
This term refers to the newborn (first four weeks).
This term refers to the child after the first year.
This type of mutation is when a nucleotide base is replaced by another, codes for alternative amino acid.
Point mutations (missense)
This type of mutation is characterized by the insertion/deletion of 1 or 2 nucleotides, which alters the "reading frame".
This type of mutation is characterized by an amplification of a sequence of 3 nucleotides.
This category of genetic disorders is also known as Mendelian disorders. They are rare and hereditary (Autosomal dominant, autosomal recessive, or X-linked recessive)
Single-gene mutations (of large effect)
How are single-gene mutations (of large effect) screened for?
Amniocentesis and ultrasonography
What are the categories of genetic disorders?
-Disorders of single-gene mutations of large effect
-Disorders of multifactorial inheritance
-Disorders of chromosomal abnormalities
-Disorders of atypical inheritance
This term refers to single mutations which may have a variety of phenotypic effects.
This term refers to multiple mutations being expressed as the same trait.
In this single gene mutation one parent is typically affected. Offspring have a 50% chance of having the disease and the most common form of expression is the heterozygous form. They are more likely to affect structural proteins and membrane receptors.
Autosomal dominant disorders
What are some factors associated with autosomal dominant disorders?
-Reduced penetrance (have the mutation, but are phenotypically normal)
-Variable expressivity (same mutation is expressed differently within different individuals
In this single gene mutation the parents are unlikely to be affected. Offspring have a 25% chance of expressing the disease and the most common form of expression is the homozygous expression. They most commonly disrupt enzymes.
Autosomal recessive disorders
In this single gene mutation heterozygous females are the ones to transmit them. Male offspring have a 50% chance of expressing the disease while female offspring are protected.
X-linked disorders (sex-linked)
This condition is autosomal dominant and characterized by a fibrillin (structural protein) gene mutation. Some characteristics include arachnodactyly, bilateral lens subluxation, ruptured aorta, and basilar invagination.
This condition is a group of single-gene disorders (autosomal dominant or recessive) caused by defective collagen synthesis. It is characterized by hyperextensible skin and hypermobile joints.
This is the most common Mendelian disorder (autosomal dominant). It is caused by a mutated LDLR gene and characterized by impaired LDL transport and catabolism.
These are cholesterol deposits on tendons.
Which familial hypercholesterolemia is more severe? Heterozygous or Homozygous.
This condition is autosomal recessive and caused by a mutation in the CFTR gene. This results in decreased chloride ion transport resulting in viscous secretions (lungs and pancreas) and increased salt in sweat.
This is the most common condition caused of death due to cystic fibrosis?
This condition is autosomal recessive and individuals who have this can't metabolize phenylalanine into tyrosine. This due to a mutated phenylanalanine hydroxylase.
This condition is autosomal recessive, which results in an abnormal galactose metabolism metabolism (mutated GALT gene). It can lead to CNS, liver, and kidney damage.
This is a group of rare autosomal recessive conditions characterized by a lack of lysosomal enzymes and an accumulation of metabolites. It can lead to CNS damage, hepatosplenomegaly, and cellular dysfunction.
Lysosomal storage diseases
Tay-Sachs disease, Niemann-Pick disease (Type A, B, C), Gaucher disease, and Mucopolysaccharidosis are examples of what type of disease?
Lysosomal storage diseases
This condition is characterized by an inability to metabolize Gm2 gangliosides due to a mutated hexosaminidase A enzyme. It can result in destruction of CNS, PNS, and ANS tissue leading to mental retardation, blindness, and motor weakness.
Tay-Sachs disease (Gm2 gangliosidosis)
What feature is characteristic of Tay-Sachs disease?
A cherry-red central macula (retina)
This condition in general is characterized by an accumulation of sphingomyelin due to a deficiency in acid sphingomyelinase
This type of Niemann-Pick disease is the most severe and results in visceromegaly and neurological damage. It is lethal by age 3.
This type of Niemann-Pick disease results in visceromegaly and no neurological damage. It is most commonly limited to hepatosplenomegaly.
This is the most common type of Niemann-Pick disease. It is a non-enzymatic deficiency characterized by defective lipid transport (mutated NPC1 or NPC2) and results in ataxia, dystonia, dysarthria, or psychomotor regression.
This condition is due to a mutated glucocerebrosidase gene resulting in the accumulation of glucocerebroside, which results in enlarged phagocytes, severe hepatosplenomegaly, osteolysis, osteonecrosis, and pancytopenia.
How many types of Gaucher disease are there?
Type I: Most common, less severe, and occurs in Ashkenazi Jews
Type II and III: more severe and have neurological disturbances
Gaucher disease creates what type of unique deformity?
Erlenmeyer flask deformity (bones)
This condition is characterized by a deficiency in ECM breakdown enzymes. Some common features include skeletal deformation ("Gargoylism"), clouding of the cornea, arterial deposits, mental retardation, joint stiffness, heart valve disease, and hepatosplenomegaly.
This type of mucopolysaccharidosis is an autosomal recessive condition, which results in α-L-iduronidase deficiency. Characteristics include corneal clouding, skeletal abnormalities, and mental retardation. It is severe and lethal by 6-10 years.
Hurler syndrome (MPS Type I)
This type of mucopolysaccharidosis is an X-linked condition, which results in an L-iduronate sulfatase deficiency. It has no corneal clouding and is slowly progressive.
Hunter syndrome (MPS Type II)
Hurler (MPS Type I) and Hunter (MPS Type II) syndromes both accumulate what two substances?
Heparan sulfate and dermatan sulfate
These are a group of inherited enzymatic deficiencies (most commonly autosomal recessive) characterized by impaired glycogen metabolism leading to glycogen accumulation in the liver, skeletal muscles, and heart
Glycogen storage diseases
This glycogen storage disease is characterized by a deficiency in glucose-6-phosphatase and decreased liver glycolysis leading to hepatomegaly and hypoglycemia.
von Gierke disease (hepatic type)
This glycogen storage disease is characterized by a deficiency in muscle phosphorylase deficiency and decreased muscle glycolysis leading to weakness/cramps.
McArdle disease (myopathic type)
This glycogen storage disease is characterized by a deficiency in lysosomal acid maltase deficiency and affects every organ, particularly the heart (cardiomegaly).
Pompe disease (Type II glycogenosis)
These disorders occur when there are greater than or equal to 2 altered genes (small effect), which have an additive influence when together.
Complex multigenic disorders
What are some features of complex multigenic disorders?
-Increased number of altered genes=increased risk
-Identical twins share risk, decreased with non-identical
-First degree relatives have similar risk,
-Expression in one offspring, increased risk in siblings
These disorders are characterized by altered chromosomes (numeric/structural).
What is the most common chomrosomal disorder?
Trisomy 21 (Down syndrome)
What are some features of Trisomy 21 (Down syndrome)?
Meiotic nondisjunction, flat facies, epicanthic folds, cardiac malformations, atlanto-axial instability
What are the common names for these autosomal cytogenic disorders? Trisomy 21, Trisomy 18, Trisomy 13, and fragmented 5th chromosome.
Trisomy 21=Down syndrome
Trisomy 18=Edwards syndrome
Trisomy 13=Patau syndrome
Fragmented 5th chromosome= Cri du chat syndrome
This condition is due to a deletion in chromosome 22, long arm (q), band 11. It results in facial dysmorphism, cardiac defects, cleft palate, cognitive delays, and hypoplasia in the thymus and/or parathyroid gland.
22q11.2 deletion syndrome
This manifestation of 22q11.2 deletion syndrome is characterized by thymic hypoplasia (decreased T cell immunity) and parathyroid hypoplasia (hypocalcemia (tetany)).
This manifestation of 22q11.2 deletion syndrome is characterized by pronounced structural defects, both facial and cardiac, and mild immunodeficiency.
These conditions have the allosome (chromosome 23) involved, are less severe and, more compatible with life. Those affected, may be phenotypically normal.
Allsomal cytogenic disorders
This term refers to X-inactivation and is typically present in allosomal cytogenetic disorders.
Lyonization (1 female X chromosome is inactivated and becomes a Barr body)
This allosomal cytogenic disorder is most commonly 47, XXY (nondisjunction during meiosis). It is the most common cause of male hypogonadism and sterility and is characterized by testicular atrophy, gynecomastia, and eunuchoid habitus.
This allosomal cytogenic disorder is due to the absence of 1 X chromosome (45, X). This is characterized by short stature, amenorrhea (streak ovaries), a decrease in secondary sex characteristics, webbed neck, aortic coarctation, cubitus valgus, and widely spaced nipples (shield chest).
What are some examples of general single gene disorders with atypical inheritance?
-Mutations in mitochondrial genes
This condition is a triple-repeat mutation that is the most common cause of familial mental retardation. Some characteristics include macroorchidism, long face, large mandible, etc.
Fragile X syndrome (FMR1 mutation)
This term is used to describe the process of features becoming more aggressive with each generation.
Diseases caused by mutation in mitochondrial genes are strictly inherited from the mother. What is the hallmark characteristic of this type of disease?
Leber hereditary optic neuropathy
This disease of genomic imprinting is due to paternal imprinting and maternal deletion of 15q12. It results in mental retardation, seizures, ataxia, and inappropriate laughing ("happy puppet syndrome").
This disease of genomic imprinting is due to maternal imprinting and paternal deletion of 15q12. It results in mental retardation, short stature, hypotonia, obesity (hyperphagia), small hands/feet, and hypogonadism.
These are structural defects, present at birth.
This type of perinatal infection occurs from the vagina or cervix. They are most commonly bacterial in origin and can cause pneumonia, meningitis, or sepsis due to inhalation of infected amniotic fluid.
Transcervical perinatal infection
This type of perinatal infection occurs by hematogenous spread. It most commonly crosses the placenta and can be parasitic, viral, or bacterial in origin.
Transplacental perinatal infection
What does TORCH stand for and what condition is it involved with?
O: other: syphilis, HIV, hepatitis B virus, tuberculosis, malaria
C: CMV (cytomegalo virus)
H: HSV (herpes simplex virus)
-It is involved with transplacental perinatal infections
This term is used to describe an individual born less than 37 weeks of gestation. It is the most common cause of neonatal mortality.
This gestational term refers to <37 weeks.
This gestational term refers to 37-38 weeks.
This gestational term refers to 39-40 weeks.
This gestational term refers to the 41st week.
This gestational term refers to > or = 42 weeks.
This material is produced by type II pneumocytes and acts to reduce surface tension in the lungs allowing for the alveoli to open upon the babies first breath.
This congenital condition is due to a decrease in surfactant production, which results in difficulty in inflating alveoli. It is also known as "Hyaline membrane disease".
Respiratory distress syndrome
This congenital condition occurs in premature babies, they require enteral feeding, and is characterized by necrosis, ulcerations, congestion, distended, and friable appearance of the intestines.
Necrotizing enterocolitis (NEC)
This condition is characterized by sudden death of infant, during sleep. It is the 3rd most common cause of death during infancy (2-4 months) and is idiopathic after autopsy.
Sudden infant death syndrome (SIDS)
What is the triple risk model of SIDS?
1. Vulnerable infant
-Hypoplasia of the arcuate nucleus
2. Critical developmental period for homeostatic control
-1 month to 1 year
3. Exogenous stressors
This condition is due to the accumulation of edema, during gestation. It is caused by fetal anemia leading to hypoxia, cardiac failure, and pooling
-Hydrops fetalis (generalized, lethal)
-Cystic hygroma (local, may not be lethal)
What are the two clinical manifestations of fetal hydrops?
-Immune hydrops: antibody-induced hemolysis
-Nonimmune: chromosomal abnormalities
What is the 1st and 2nd most common cause of death from 4-14 years.
What are the three benign pediatric tumors?
This is the most common germ cell tumor of childhood and occurs at the base of the coccyx.
What tissues are the most commonly affected in pediatric malignant tumors.
Hematopoietic, neuronal, and soft tissues
What are three unique pediatric cancers?
This is a pediatric malignancy of neural crest-derived cells and have tumor cells that surround a neutrophil in a rosette pattern (Home-Wright pseudo-rosette), which have the potential (90%) to secrete catecholamines. The younger you are when diagnosed the more favorable of a prognosis.
This is a pediatric malignancy of the posterior retina. It most commonly occurs at the age of 2 and has two types (genetic and sporadic). It is commonly characterized by flexner-wintersteiner rosettes.
This type of retinoblastoma is characterized by multiple and bilateral tumors in the retina.
This type of retinoblastoma is characterized by isolated and unilateral tumors in the retina.
This feature is described as cuboidal cells surrounding an empty lumen and is a hallmark feature of retinoblastoma.
This is a pediatric malignancy of the kidney. It most commonly occurs between the ages of 2-5 years and presents as a palpable mass with abdominal pain, fever, and hematuria.
Wilms tumor (nephroblastoma)
What three syndromes are associated with Wilms tumor?
-WAGR syndrome (Wilms tumor, Aniridia, Genitourinary, and mental Retardation)
-Denys-Drash syndrome (DDS)
-Beckwith-Wiedemann syndrome (BWS)
What procedures are performed to detect prenatal indications of genetic disease?
Amniocentesis, umbilical cord blood, or biopsy