Niemann-Pick Disease Overview

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Questions and Answers

What type of disorder is primarily associated with defects in connective tissues?

Thalassemias

Muscular dystrophies

Marfan syndrome (correct)

Hemoglobinopathies

Which genetic condition is characterized by a defect in collagen synthesis?

Hereditary spherocytosis

G6PD deficiency

Osteogenesis imperfecta (correct)

Marfan syndrome

What percentage of Marfan syndrome cases are estimated to be familial?

50% to 60%

70% to 85% (correct)

100%

15% to 30%

Which of the following best describes pharmacogenetics?

Study of how genes influence drug responses Signup and view all the answers

What is a well-known genetic factor that can lead to severe adverse reactions when exposed to specific drugs?

G6PD deficiency Signup and view all the answers

What genetic event primarily leads to trisomy 21?

Meiotic nondisjunction of chromosome 21 in the ovum Signup and view all the answers

What is the characteristic clinical feature observed in the early stages of Niemann-Pick disease?

Cherry-red spot in the macula Signup and view all the answers

Which gene is overexpressed in individuals with trisomy 21?

APP (amyloid-beta precursor protein) Signup and view all the answers

What causes Niemann-Pick disease types A and B?

Inherited deficiency of sphingomyelinase Signup and view all the answers

What is a common clinical feature of infants with trisomy 21?

Flat facial profile and epicanthic folds Signup and view all the answers

What characterizes trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome) compared to trisomy 21?

Malformations are more severe and wide ranging. Signup and view all the answers

In which population is Niemann-Pick disease most prevalent?

Ashkenazi Jews Signup and view all the answers

Which gene is associated with the development of facial structures, thymus, and parathyroid glands in 22q11.2 deletion syndrome?

TBX1 Signup and view all the answers

What type of inheritance pattern is associated with Niemann-Pick disease?

Autosomal recessive Signup and view all the answers

What is a clinical feature of 22q11.2 deletion syndrome?

Abnormalities of the palate Signup and view all the answers

What is one of the dominant histologic changes seen in Niemann-Pick disease?

Vacuolation and ballooning of neurons Signup and view all the answers

How prevalent is the 22q11.2 deletion syndrome?

1 in 4000 births Signup and view all the answers

What is the likely outcome for patients with type A Niemann-Pick disease?

Early death within the first three years of life Signup and view all the answers

What term describes the membranous cytoplasmic bodies found in Niemann-Pick disease?

Zebra bodies Signup and view all the answers

What typically characterizes individuals with trisomy 21 at birth?

Epicanthic folds and flat facial profiles Signup and view all the answers

Which statement accurately describes Niemann-Pick type B?

It does not include central nervous system involvement. Signup and view all the answers

What is described by incomplete penetrance?

Individuals inherit the mutant gene but are phenotypically normal. Signup and view all the answers

What is variable expressivity?

The trait is seen in individuals carrying the mutant gene but expressed differently. Signup and view all the answers

In autosomal recessive disorders, what is the likelihood of siblings sharing the disease trait if both parents carry the recessive gene?

25% Signup and view all the answers

What is a characteristic feature of autosomal recessive disorders?

Expression of the defect tends to be uniform with complete penetrance. Signup and view all the answers

What is the relationship between X-linked disorders and gender?

Both genders can be affected but mostly males are symptomatic. Signup and view all the answers

Which statement about the genotype and phenotype of X-linked disorders is accurate?

Phenotype can be full expression, partial expression, or no expression of the mutation. Signup and view all the answers

What type of inheritance pattern comes from a consanguineous marriage in the context of autosomal recessive disorders?

Low frequency recessive alleles are more likely to appear. Signup and view all the answers

What is a significant underlying cause of most autosomal recessive disorders?

Often involved enzyme proteins. Signup and view all the answers

Which of the following patterns is NOT characteristic of autosomal dominant diseases?

Involvement of enzyme proteins. Signup and view all the answers

What can be inferred about Y-linked disorders?

Males affected by mutations are typically infertile. Signup and view all the answers

What is a key characteristic of Leber hereditary optic neuropathy?

It leads to bilateral loss of central vision. Signup and view all the answers

Which of the following best describes paternal imprinting?

It occurs in the ovum or sperm before fertilization. Signup and view all the answers

What genetic disorder is characterized by obesity, short stature, and profound hyperphagia?

Prader-Willi syndrome Signup and view all the answers

Which chromosome is associated with the deletions that lead to Prader-Willi syndrome?

Chromosome 15 Signup and view all the answers

What is NOT a manifestation of Leber hereditary optic neuropathy?

Ataxic gait Signup and view all the answers

What happens with the maternal 15q12 chromosome in Prader-Willi syndrome?

It is imprinted, leading to its functional alleles being provided by the paternal chromosome. Signup and view all the answers

What is a common feature of Angelman syndrome?

Happy demeanor and inappropriate laughter Signup and view all the answers

In genomic imprinting, what process occurs before fertilization?

Alleles are silenced in the ovum or sperm. Signup and view all the answers

Study Notes

Incomplete Penetrance & Variable Expressivity

Incomplete penetrance occurs when individuals inherit a mutant gene but remain phenotypically normal.
Variable expressivity means the trait is observable in all carriers of a mutant gene but manifests differently among them (e.g., Neurofibromatosis type 1).
Delayed age of onset is common in certain autosomal dominant diseases.
Autosomal dominant diseases can involve regulation of complex metabolic pathways or key structural proteins like collagen.

Autosomal Recessive Disorders

Genotype for autosomal recessive disorders is typically homozygous recessive (aa).
Phenotype usually expressed only when both recessive alleles are inherited.
Frequently involve enzyme proteins; males and females are equally affected.
Siblings have a 25% chance of displaying the disease if both parents are carriers.
Low frequency mutant genes often indicate consanguineous marriages.
Expression of defects is generally uniform with complete penetrance, onset is often early, but they may remain clinically undetected.
Commonly include inborn errors of metabolism.

X-Linked Disorders

Genotype is influenced heavily by the X chromosome, can be dominant or recessive.
Phenotypic expression can be complete, partial, or absent.
Most sex-linked disorders are X-linked and typically recessive; males with mutations affecting Y-linked genes are usually infertile.
Types of X-linked disorders include hemoglobinopathies (defects in globin structure), thalassemias (deficits in globin synthesis), and defects in structural proteins like collagen and dystrophin.

Genetically Determined Adverse Reactions to Drugs

Pharmacogenetics studies how genetics influence response to medications.
Certain enzyme deficiencies manifest only after drug exposure, significantly impacting drug sensitivity and adverse reactions (e.g., G6PD deficiency and primaquine leading to hemolytic anemia).

Disorders Associated with Defects in Structural Proteins

Marfan Syndrome

Connective tissue disorder affecting skeleton, eyes, and cardiovascular system.
Prevalence is about 1 in 5,000; 70-85% familial (autosomal dominant) and 15-30% arise from new mutations.
Clinical signs include a characteristic cherry-red spot in the macula of the eye, which appears early in the disease course.

Niemann-Pick Disease Types A and B

Lysosomal disorder characterized by sphingomyelin accumulation due to sphingomyelinase deficiency.
Most often diagnosed in Ashkenazi Jews; primarily an autosomal recessive condition.
Pathology includes vacuolation of neurons and the presence of zebra bodies.
Type A is a severe form with early neurologic involvement; Type B has organomegaly but minimal CNS impact.

Trisomy Disorders

Trisomy 21 (Down syndrome) results from meiotic nondisjunction, leading to overexpression of genes on chromosome 21, including APP.
Clinical features include distinct facial characteristics and various organ system abnormalities.
Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome) are more severe, with infants rarely surviving beyond the first year.

Chromosome 22q11.2 Deletion Syndrome

Results from deletion on chromosome 22, affecting multiple developmental processes.
Prevalence is around 1 in 4,000 births.
Clinical manifestations include congenital heart defects, cleft palate, facial dysmorphism, and immunodeficiencies.
Disorders stemming from this deletion can include DiGeorge syndrome and velocardiofacial syndrome.

Genomic Imprinting

Imprinting refers to the differential expression of paternal and maternal alleles.
Maternal imprinting silences the maternal allele; paternal imprinting silences the paternal allele.
Illustrated by Prader-Willi syndrome (paternal deletion) and Angelman syndrome (maternal deletion).
Prader-Willi syndrome is characterized by obesity and intellectual disability, while Angelman syndrome features microcephaly and ataxia.
Three mechanisms of genomic imprinting include chromosomal deletions that lead to syndromes depending on which parent's allele is affected.

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Description

Explore the characteristics and progression of Niemann-Pick Disease Types A and B. This quiz covers the early signs, diagnostic methods, and the impact on patients' lives. Test your knowledge on this critical topic in medical genetics.