Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Genetics > Goljan - Genetic and Developmental Disorders Chapter > Flashcards

Goljan - Genetic and Developmental Disorders Chapter Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

Sickle cell disease

A

Sickle hemoglobin; autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Cystic fibrosis

A

Cystic fibrosis transmembrane regulator (CFTR); autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Familial hypercholesterolemia

A

Low-density lipoprotein (LDL) receptor; autosomal dominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Neurofibromatosis

A

Neurofibromin; autosomal dominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Hemophilia A

A

Factor VIII; X-linked recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Deficient enzyme in alkaptonuria

A

Homogentisate oxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Clinical findings in alkaptonuria

A
  1. Black urine (undergoes oxidation when exposed to light)
  2. Black pigmentation of nose, ears, cheeks
  3. Black cartilage in joints and intervertebral discs, producing degenerative arthritis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Biochemical findings in alkaptonuria

A
  1. Increased homogentisate (black pigment), which binds to collagen in connective tissue, tendons, cartilage
  2. Decreased maleylacetoacetate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Deficient enzyme in galactosemia

A

Galactose-1-phosphate uridyltransferase (GALT)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Biochemical findings in galactosemia

A
  1. Increased galactose-1-phosphate –> toxic to liver and CNS
  2. Increased galactose in urine
  3. Increased galactitol –> sugar alcohol that produces osmotic damage in lens
  4. Decreased glucose-1-phosphate
  5. Decreased glucose-6-phosphate
  6. Decreased blood glucose in fasting state
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Clinical findings in galactosemia

A
  1. Mental retardation
  2. Cirrhosis
  3. Fasting hypoglycemia (due to decrease in gluconeogenic substrates distal to block)
  4. Cataracts (due to osmotic damage)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Treatment for galactosemia

A

Avoid dairy products (galactose derives from lactose)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Deficient enzyme in hereditary fructose intolerance

A

Aldolase B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Biochemical findings in hereditary fructose intolerance

A
  1. Increase in fructose-1-phosphate –> toxic substrate
  2. Decreased glyceraldehyde-3-phosphate
  3. Decreased dihydroxyacetone phosphate (DHAP)
  4. Decreased glucose in the fasting state
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Clinical findings in hereditary fructose intolerance

A
  1. Cirrhosis
  2. Hypoglycemia (due to decrease in gluconeogenic substrates)
  3. Hypophosphatemia (used up in phosphorylating fructose)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Treatment for hereditary fructose intolerance

A

Avoid fructose (e.g., in honey) and sucrose (glucose + fructose)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Deficient enzyme in homocystinuria

A

Cystathionine synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Biochemical findings in homocystinuria

A
  1. Increased homocysteine and methionine levels

2. Decreased cystathionine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Clinical findings in homocystinuria

A
  1. Mental retardation
  2. Vessel thrombosis (due to homocysteine accumulation)
  3. Lens dislocation and arachnodactyly (similar to Marfan syndrome)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Deficient enzyme in maple syrup urine disease

A

Branched chain alpha-ketoacid dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Biochemical findings in maple syrup urine disease

A
  1. Increased isoleucine –> decreased acetyl CoA + decreased succinyl CoA
  2. Increased leucine –> decreased acetyl CoA + acetoacetate
  3. Increased valine –> decreased succinyl CoA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Clinical findings in maple syrup urine disease

A
  1. Mental retardation
  2. Seizures
  3. Feeding problems
  4. Sweet-smelling urine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Deficient enzyme in phenylketonuria

A

Phenylalanine hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Biochemical findings in phenylketonuria

A
  1. Increased levels of phenylalanine and neurotoxic byproducts
  2. Decreased levels of tyrosine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Clinical findings in phenylketonuria

A
  1. Mental retardation
  2. Microcephaly
  3. Mousy odor (due to conversion of phenylalanine into phenylacids)
  4. Decreased skin pigmentation (melanin derives from tyrosine, the levels of which are reduced)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Treatment for phenylketonuria

A
  1. Restrict phenylalanine; avoid sweeteners containing phenylalanine (e.g., NutraSweet)
  2. Add tyrosine to diet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Pregnant women with PKU must be on a…or their newborns will be…at birth.

A

Phenylalanine-free diet; mentally retarded

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Hereditary angioedema

A

C1 esterase inhibitor deficiency; autosomal dominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Deficient enzyme in “malignant” phenylketonuria

A

Dihydropterin reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Accumulated substrates in “malignant” phenylketonuria

A

Phenylalanine and neurotoxic byproducts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Treatment for “malignant” phenylketonuria

A
  1. Restrict phenylalanine in diet
  2. Administer L-dopa and 5-hydroxytryptophan to replace neurotransmitters
  3. Administer BH4 (i.e., tetrahydrobiopterin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Patients with “malignant” phenylketonuria are unable to metabolize…or…, resulting in decreased synthesis of…and…, respectively.

A

Tryptophan; tyrosine; serotonin; dopamine

Note: Metabolism of both tryptophan and tyrosine requires BH4.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Deficient enzyme in McArdle disease

A

Muscle glycogen phosphorylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Biochemical findings in McArdle disease

A
  1. Increased glycogen

2. Decreased glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Clinical findings in McArdle disease

A
  1. Glycogenosis with muscle fatigue
  2. Propensity for rhabdomyolysis with myoglobinuria
  3. No lactic acid increase with exercise due to lack of glucose in muscle and a corresponding lack of anaerobic glycolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Deficient enzyme in Pompe disease

A

Alpha-1,4-glucosidase (lysosomal enzyme)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Clinical findings in Pompe disease

A
  1. Glycogenosis

2. Cardiomegaly with early death from heart failure (or, to be more specific, restrictive cardiomyopathy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Accumulated substrate in patients with Pompe disease

A

Glycogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Deficient enzyme in von Gierke disease

A

Glucose-6-phosphatase (gluconeogenic enzyme)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Biochemical findings in patients with von Gierke disease

A
  1. Increased glucose-6-phosphate

2. Decreased glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Clinical findings in von Gierke disease

A
  1. Glycogenosis
  2. Enlarged liver and kidneys (both contain gluconeogenic enzymes)
  3. Fasting hypoglycemia (no response to glucagon or other gluconeogenesis stimulators)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Deficient enzyme in Gaucher disease (type I)

A

Glucocerebrosidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Most common lysosomal storage disease

A

Gaucher disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Clinical findings in Gaucher disease type I

A
  1. Hepatosplenomegaly
  2. Fibrillar-appearing macrophages in liver, spleen, and bone marrow
  3. Pancytopenia from marrow involvement
  4. Hypersplenism from enlarged spleen

Note: There is no CNS involvement.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Treatment for Gaucher disease

A

Replacement therapy with recombinant enzyme is effective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Deficient enzyme in Hurler syndrome

A

Alpha-1-iduronidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Biochemical findings in Hurler syndrome

A

Dermatan and heparin sulfate (mucopolysaccharides or glycosaminoglycans) accumulate in mononuclear phagocytic cells, lymphocytes, endothelial cells, intimal smooth muscle cells, and fibroblasts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Describe the typical clinical course of Hurler syndrome.

A

Normal at birth but develop severe mental retardation and hepatosplenomegaly by 6-24 months.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Clinical features of Hurler syndrome

A
  1. Coarse facial features
  2. Short neck
  3. Corneal clouding
  4. Coronary artery disease
  5. Vacuoles in circulating lymphocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

A milder form of Hurler syndrome is…, which is characterized by an…inheritance pattern.

A

Hunter syndrome; X-linked recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Deficient disease in Niemann-Pick disease

A

Sphingomyelinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Accumulated substrate in Niemann-Pick disease

A

Sphingomyelin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

…are present in 30-50% of Niemann-Pick cases.

A

Cherry red macula

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Signs and symptoms of Niemann-Pick disease begin…

A

At birth.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Niemann-Pick disease type A is very severe and involves the…

A

CNS, causing psychomotor dysfunction and shortened lifespan.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Niemann-Pick disease type B does not involve the CNS and pts…

A

Survive into adulthood.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Laboratory findings in cases of Niemann-Pick disease

A

Phagocytic cells affected in liver (hepatomegaly), spleen (massive splenomegaly), lymph nodes, and bone marrow. Phagocytes have a foamy appearance; zebra bodies are seen on EM.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Deficient enzyme in Tay-Sachs disease

A

Hexosaminidase A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Accumulated substrate in Tay-Sachs disease

A

GM2 ganglioside

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Describe the typical clinical course of Tay-Sachs disease.

A

Normal at birth but manifest signs and symptoms by 6 months of age.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Clinical findings in Tay-Sachs disease

A
  1. Muscle weakness
  2. Mental deterioration
  3. Whorled configurations in neurons
  4. Cherry-red macula (pale ganglion cells with excess gangliosides accentuate the normal red color of the macular choroid)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Give four examples of autosomal recessive disorders

A
  1. Hemochromatosis
  2. 21-hydroxylase deficiency
  3. Wilson disease
  4. Thalassemia
63
Q

An increase in normal glycogen in tissue would be seen in…, while an increase in structurally abnormal glycogen in tissue would be seen in…

A

von Gierke disease; debranching enzyme deficiency

64
Q

Glycogen deposition in tissue produces restrictive heart disease in…and hepatorenomegaly in…

A

Pompe disease; von Gierke disease

65
Q

Most common autosomal recessive disorder

A

Hemochromatosis

66
Q

In adult polycystic kidney disease (AD disorder), cysts are…

A

Not present at birth.

67
Q

In familial polyposis (AD disorder), polyps are…

A

Not present at birth.

68
Q

Familial polyposis is characterized by…penetrance.

A

Complete

69
Q

Marfan syndrome is characterized by…penetrance.

A

Incomplete

70
Q

If all individuals with a mutant gene express a particular disorder but at different levels of severity, then this is known as…

A

Variable expressivity.

71
Q

Give an example of an autosomal dominant disease that exhibits variable expressivity.

A

Neurofibromatosis; some pts may have a few cafe au lait spots (coffee-colored flat lesions), while others have numerous neurofibromas (pedunculated, pigmented lesions)

72
Q

Male-to-male disease transmission is characteristic of…

A

Autosomal dominant inheritance.

73
Q

Give some examples of diseases inherited in an autosomal dominant manner.

A
  1. HD
  2. Osteogenesis imperfecta
  3. Achondroplasia
  4. Tuberous sclerosis
  5. Hereditary spherocytosis
  6. von Willebrand disease
  7. Myotonic dystrophy
  8. Familial hypercholesterolemia
74
Q

Most common autosomal dominant disorder

A

von Willebrand disease

75
Q

Enzyme deficiencies are…in autosomal dominant disorders.

A

Relatively uncommon

76
Q

…are the most common type of proteins affected in X-linked recessive disorders.

A

Enzymes

77
Q

Fragile X syndrome (FXS) is an…trinucleotide repeat disorder.

A

X-linked recessive

78
Q

Most common Mendelian disorder causing mental retardation

A

Fragile X syndrome

79
Q

What is the genetic defect in FXS?

A

At the distal end of the long arm of the X chromosome (band Xq27.3), CGG amplification produces a constriction that gives the appearance of a fragile portion of the X chromosome; the familial mental retardation-1 (FMR1) gene is located at this site; loss of function of this gene, which is most abundantly expressed in the brain and testis, is responsible for mental retardation in FXS

80
Q

Clinical findings in FXS

A
  1. Affected males have mental retardation with an IQ range of 20-70
  2. Females with FXS and less affected males have IQs that approach 80
  3. Facial changes – long face, large mandible, everted ears, arched palate
  4. Macro-orchidism (enlarged testes) at puberty is almost universal
  5. Mitral valve prolapse
  6. Pectus excavatum
  7. Scoliosis
  8. Hyperextensible joints
81
Q

Normal testicular volume at puberty is…, whereas in individuals with FXS, the volume is…

A

17 mL; >25 mL

82
Q

Best test for diagnosis of FXS

A

DNA analysis (PCR) to identify trinucleotide repeats

83
Q

Lesch-Nyhan syndrome is due to deficiency of…

A

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

84
Q

HGPRT is normally involved in…

A

Salvaging the purines hypoxanthine and guanine.

85
Q

Clinical findings in Lesch-Nyhan syndrome

A
  1. Mental retardation
  2. Hyperuricemia
  3. Self-mutilation
86
Q

Give some examples of X-linked recessive disorders.

A
  1. Androgen insensitivity syndrome
  2. Chronic granulomatous disease
  3. Bruton agammaglobulinemia
  4. Glucose-6-phosphate dehydrogenase deficiency
87
Q

What distinguishes X-linked dominant disorders from autosomal dominant disorders?

A

There is no male-to-male transmission observed in X-linked dominant disorders.

88
Q

Vitamin D-resistant rickets is an…that involves…

A

X-linked dominant disorder; defective renal and gastrointestinal reabsorption of phosphate

89
Q

The…observed in patients with vitamin D-resistant rickets results in…

A

Hypophosphatemia; defective bone mineralization (i.e., osteomalacia), because phosphate is required to drive calcium into bone

90
Q

What is the Lyon hypothesis?

A

In females, one of the two X chromosomes (X paternal, X maternal) is randomly inactivated.

91
Q

Random X inactivation occurs on day…of embryonic development.

A

16

92
Q

An inactivated X chromosome is known as a…

A

Barr body.

93
Q

Barr bodies are found attached to the…of cells and can be counted in…

A

Nuclear membrane; squamous cells obtained by scraping the buccal mucosa

94
Q

Unequal separation of chromosomes in meiosis

A

Nondisjunction

95
Q

Examples of diseases caused by nondisjunction

A
  1. Turner syndrome (22 + 23 = 45 chromosomes)

2. Down syndrome (24 + 23 = 47 chromosomes)

96
Q

Nondisjunction of chromosomes during mitosis in the early embryonic period

A

Mosaicism; two chromosomally different cell lines are derived from a single fertilized egg

97
Q

Mosaicism most often involves…

A

Sex chromosomes (e.g., in Turner syndrome)

98
Q

Transfer of chromosome parts between nonhomologous chromosomes

A

Translocation

99
Q

Translocation in which translocated fragment is functional

A

Balanced translocation

100
Q

A balanced translocation between two acrocentric chromosomes is known as a…

A

Robertsonian translocation

101
Q

In an acrocentric chromosome, the centromere is…

A

Near the end of the chromosome

102
Q

Loss of the short arm of chromosome 5 causes…

A

Cri du chat syndrome

103
Q

Clinical findings in cri du chat syndrome include…

A
  1. Mental retardation
  2. Cat-like cry
  3. Ventricular septal defect (VSD)
104
Q

In one type of Down syndrome, the mother of an affected child has 45 (not 46) chromosomes because of a…between the long arms of chromosomes…

A

Robertsonian translocation; 21 and 14

105
Q

Causes of Down syndrome

A
  1. Nondisjunction (95% of cases, trisomy 21)
  2. Robertsonian translocation (4% of cases, 46 chromosomes)
  3. Mosaicism (1% of cases)
106
Q

Major risk factor for Down syndrome

A

Increased maternal age

107
Q

Meiotic nondisjunction of chromosome 21 occurs in…, usually during

A

Oogenesis; meiosis I

108
Q

Approximately…of concepti with trisomy 21 die in embryonic or fetal life.

A

75%

109
Q

Some clinical findings in Down syndrome

A
  1. Mental retardation – pts have mild retardation (IQ 50-75; usually mosaics) or severe retardation (IQ 20-35)
  2. Muscle hypotonia is present at birth
  3. Upslanting of palpebral fissures
  4. Epicanthic folds
  5. Flat facial profile
  6. Macroglossia with protuberant tongue
  7. Simian crease
  8. Heart defects (40-50% of pts)
  9. Umbilical hernia
  10. Gap between 1st and 2nd toe
  11. Atlantoaxial instability (danger of spinal cord compression)
110
Q

Most common cause of “floppy baby” syndrome

A

Down syndrome

111
Q

Most common chromosomal abnormality associated with mental retardation

A

Down syndrome

112
Q

What is the major factor affecting survival in early childhood in pts with Down syndrome?

A

Heart defects

113
Q

Which specific heart defects are seen in pts with Down syndrome?

A
  1. Endocardial cushion defects (43%)
  2. VSD (32%)
  3. ASD (10%)
  4. Tetralogy of Fallot (6%)
  5. Isolated patent ductus arteriosus (4%)
114
Q

GI tract abnormalities in Down syndrome

A
  1. Tracheoesophageal fistula – proximal esophageal ends blindly and distal esophagus arises from trachea
  2. Duodenal atresia – atresia of the small bowel distal to where the common bile duct empties; characterized by vomiting of bile stained fluid at birth
  3. Hirschsprung disease – aganglionic segment in large bowel; problem with stooling at birth
115
Q

Hematologic abnormalities in Down syndrome

A

Increased risk for developing leukemia; acute lymphoblastic leukemia (ALL) and acute megakaryocytic leukemia are the most common types of leukemia; leukemia is usually preceded by transient myeloproliferative diseases

116
Q

CNS abnormalities in Down syndrome

A

Most pts develop the neuropathologic signs of Alzheimer disease by 35-40 years of age.

117
Q

…is the major factor affecting survival in older individuals with Down syndrome.

A

Alzheimer disease

118
Q

…codes for amyloid precursor protein, which is the precursor for…

A

Chromosome 21; ABeta protein

119
Q

Immune abnormalities in pts with Down syndrome

A

Increased risk for developing:

  1. Hypothyroidism secondary to Hashimoto thyroiditis
  2. Lung infections
  3. Diabetes mellitus
120
Q

Males with Down syndrome are usually unable…, while females with Down syndrome exhibit decreased…and an increased…

A

To father children; fertility; incidence of miscarriages

121
Q

Which laboratory findings during pregnancy suggest a mother is carrying a child with Down syndrome?

A
  1. Decreased serum alpha-fetoprotein (AFP)
  2. Decreased urine unconjugated estriol (uE3)
  3. Increased serum human chorionic gonadotropin (hCG)
122
Q

Invasive diagnostic tests for Down syndrome include:

A
  1. Amniocentesis with chorionic villous sampling
  2. Percutaneous umbilical blood sampling
  3. Cytogenetic and DNA studies used to confirm the diagnosis
123
Q

Second most common trisomy syndrome

A

Trisomy 18 (Edwards syndrome)

124
Q

Clinical findings in Edwards syndrome

A
  1. Mental retardation
  2. Clenched fist with overlapping fingers
  3. Rocker-bottom feet (also seen in trisomy 16)
  4. VSD
  5. Early death
125
Q

Trisomy 13 is also known as…

A

Patau syndrome

126
Q

Clinical findings in Patau syndrome

A
  1. Mental retardation
  2. Cleft lip and palate
  3. Polydactyly
  4. VSD
  5. Cystic kidneys
  6. Early death
127
Q

Most common sex chromosome abnormality in females

A

Turner syndrome

128
Q

Pts with Turner syndrome exhibit…

A

Normal intelligence

129
Q

Karyotypic abnormalities in Turner syndrome

A
  1. 45,X karyotype (most conceptuses are nonviable; majority are due to a paternal nondisjunction)
  2. Mosaicism (most common cause of Turner syndrome) – 45,X/46,XX karyotype is most commonly seen; 45,X/46,XY karyotype is also observed (these pts are at increased risk for developing gonadoblastoma of the ovary)
130
Q

As many as…of spontaneous abortions are due to Turner syndrome.

A

15%

131
Q

Clinical findings in Turner syndrome

A
  1. Short stature is a cardinal finding (>95% of cases); due to deletion of a second SHOX gene located on the X chromosome
  2. Carrying angle of the arms is increased (cubitus valgus)
  3. Short fourth metacarpal or metatarsal bone produces the knuckle (index finger)-knuckle-dimple (short 4th metacarpal/metatarsal bone)-knuckle sign (Archibald’s sign)
  4. Shield chest with widely spaced nipples and underdeveloped breasts is present
  5. Pubic hair development is normal
  6. Lymphedema may occur in the hands, feet, and neck in infancy
132
Q

Lab findings in Turner syndrome

A
  1. Growth hormone and insulin-like growth factor-1 are normal
  2. Estradiol and progesterone levels are decreased
  3. FSH and LH levels are increased
133
Q

What causes the webbed neck in Turner syndrome?

A

Dilated lymphatic channels (cystic hygroma)

134
Q

Cardiovascular abnormalities in Turner syndrome

A

Congenital heart disease occurs in 20-50% of cases; a hypoplastic left heart is the major cause of mortality in early infancy; preductal coarctation commonly occurs and often presents with left-sided heart failure; bicuspid aortic valves are another common cardiac abnormality

135
Q

Genitourinary abnormalities in Turner syndrome

A
  1. Both ovaries are replaced by fibrous stroma (called streak gonads); results in increased risk for developing ovarian dysgerminoma
  2. Ovaries are devoid of oocytes by two years of age
  3. Primary amenorrhea occurs with delayed sexual maturation
  4. Incidence of horseshoe kidneys in increased
136
Q

Most common genetic cause of primary amenorrhea

A

Turner syndrome

137
Q

Hypothyroidism due to…occurs in 10-30% of cases.

A

Hashimoto thyroiditis

138
Q

Most common genetic cause of male hypogonadism

A

Klinefelter syndrome

139
Q

Causes of Klinefelter syndrome

A
  1. Nondisjunction is the most common cause (90% of cases); produces 47 chromosomes with an XXY karyotype; maternal and paternal nondisjunction in meiosis I occurs in roughly equal proportions
  2. Mosaicism is the remaining cause of the syndrome, with the most common karyotype being 46,XY/47,XXY
140
Q

In Klinefelter syndrome, testicular abnormalities and female secondary sex characteristics do not develop until…

A

Puberty.

141
Q

In pts with Klinefelter syndrome, testicular volume at puberty is…and is due to…

A

Decreased (

142
Q

Histologic exam of the testes in pts with Klinefelter syndrome reveals…

A

Fibrosis of seminiferous tubules with absence of spermatogenesis (azoospermia; infertility) and loss of Sertoli cells

143
Q

Loss of Sertoli cells in Klinefelter syndrome leads to a…and a corresponding increase in…

A

Decrease in inhibit; FSH (due to loss of negative feedback from inhibin)

144
Q

…in pts with Klinefelter syndrome are prominent because of atrophy of other portions of the testis.

A

Leydig cells

145
Q

Increased FSH levels in Klinefelter syndrome increases synthesis of…in Leydig cells.

A

Aromatase

Note: Increased synthesis of aromatase very likely converts a little of the testosterone that is synthesized by the Leydig cells into estradiol. However, this does not fully explain why pts with Klinefelter syndrome have hypogonadism and feminization.

146
Q

Primary reason for hypogonadism and feminization in Klinefelter syndrome is that…

A

Testosterone does not have a normal interaction with androgen receptors; the gene on the X chromosome that is responsible for androgen receptor synthesis contains CAG trinucleotide repeats; the functional response to testosterone is dependent on the number of CAG repeats in the androgen receptor; testosterone interacts better with androgen receptors that have the smallest number of CAG repeats; in Klinefelter syndrome, the X chromosome with the shortest stretch of CAG repeats is preferentially inactivated, leaving behind androgen receptors that have the longest CAG repeats; testosterone does not interact with androgen receptors with the longest CAG repeats, which, along with increased conversion of testosterone into estradiol by aromatase, causes hypogonadism and leaves estradiol unopposed by any androgen effects, causing feminization

147
Q

Signs of male hypogonadism in Klinefelter syndrome

A
  1. Persistent gynecomastia
  2. Facial, body, and pubic hair are diminished
  3. Hair distribution in the pubic region resembles that of a female (i.e., there is a lack of extension of hair from the mons pubis to the umbilicus)
  4. Penis is small (micropenis) because of decreased fetal production of testosterone in utero
  5. Testicular volume is decreased from testicular atrophy
148
Q

Describe the body habitus of pts with Klinefelter syndrome.

A

Eunuchoid body habitus with disproportionately long legs

149
Q

Intelligence in Klinefelter syndrome

A
  1. Mean IQ is lower than normal
  2. Minor developmental and learning disabilities are present in most cases
  3. In pts that have more than two X chromosomes, the IQ is lower.
150
Q

Cardiovascular abnormality present in 50% of adults with Klinefelter syndrome

A

Mitral valve prolapse

151
Q

Endocrine abnormalities seen in pts with Klinefelter syndrome

A

Increased incidence of type 2 diabetes mellitus and metabolic syndrome (insulin resistance)

152
Q

Lab findings in Klinefelter syndrome

A
  1. Decreased serum testosterone and increased serum LH
  2. Increased serum FSH and estradiol
  3. Decreased serum inhibin
  4. Azoospermia (no sperm)
153
Q

Pts with Klinefelter syndrome are at increased risk for developing…

A
  1. SLE
  2. Rheumatoid arthritis
  3. Sjogren syndrome
  4. Breast cancer
  5. Osteoporosis
154
Q

XYY syndrome is due to…and is associated with…

A

Paternal nondisjunction; aggressive (sometimes criminal) behavior and normal gonadal function

Genetics (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions