USMLE Guide: Pediatric Genetic Disorders

Introduction

Pediatric genetic disorders refer to a group of conditions that are caused by abnormalities in an individual's genetic material. These disorders can affect various aspects of a child's development and health, and they often have lifelong implications. As a healthcare professional preparing for the USMLE, it is essential to have a solid understanding of pediatric genetic disorders, including their etiology, clinical features, and management. This guide aims to provide you with a comprehensive overview of key concepts related to pediatric genetic disorders.

I. Overview of Genetic Disorders

A. Definition

• Pediatric genetic disorders are conditions caused by alterations or mutations in an individual's DNA.
• These alterations can occur in genes, chromosomes, or other structural elements of DNA.
• Genetic disorders can be inherited from parents or arise sporadically due to de novo mutations.

B. Classification

• Genetic disorders can be broadly classified into three categories:
  1. Single-gene disorders: Caused by mutations in a single gene.
  2. Chromosomal disorders: Caused by abnormalities in the structure or number of chromosomes.
  3. Multifactorial disorders: Caused by a combination of genetic and environmental factors.

C. Prevalence

• The prevalence of genetic disorders varies widely, with some being relatively common and others extremely rare.
• Certain genetic disorders are more prevalent in specific populations due to genetic drift or founder effects.
• Advances in genetic testing have led to improved identification and diagnosis of these disorders.

II. Single-Gene Disorders

A. Autosomal Dominant Disorders

• Autosomal dominant disorders result from a mutation in a single copy of an autosomal gene.
• The affected individual has a 50% chance of passing on the disorder to each child.
• Examples: Neurofibromatosis type 1, Marfan syndrome.

B. Autosomal Recessive Disorders

• Autosomal recessive disorders require mutations in both copies of an autosomal gene.
• Affected individuals often have unaffected parents who are carriers of the mutated gene.
• Examples: Cystic fibrosis, sickle cell disease.

C. X-Linked Disorders

• X-linked disorders are caused by mutations in genes located on the X chromosome.
• Males are typically more severely affected due to the presence of only one X chromosome.
• Examples: Duchenne muscular dystrophy, hemophilia A.

III. Chromosomal Disorders

A. Trisomy Disorders

• Trisomy disorders occur when there is an extra copy of a particular chromosome.
• The most common trisomy disorder is Down syndrome (trisomy 21).
• Trisomy disorders often result in intellectual disabilities and characteristic physical features.

B. Deletion and Duplication Disorders

• Deletion disorders involve the loss of a portion of a chromosome.
• Duplication disorders involve the presence of an extra copy of a portion of a chromosome.
• Examples: Cri-du-chat syndrome (5p deletion), Prader-Willi syndrome (15q deletion).

C. Translocation Disorders

• Translocation disorders occur when a portion of one chromosome is transferred to another chromosome.
• Balanced translocations may not cause any health problems, but can increase the risk of having a child with an unbalanced translocation.
• Examples: Chronic myeloid leukemia (Philadelphia chromosome), familial Down syndrome (translocation involving chromosome 21).

IV. Multifactorial Disorders

A. Definition

• Multifactorial disorders result from a combination of genetic predisposition and environmental factors.
• They are typically characterized by a complex interplay of multiple genes and environmental influences.
• Examples: Congenital heart defects, cleft lip and palate.

B. Risk Factors

• Family history of the disorder increases the risk for an individual to develop the disorder.
• Environmental factors such as maternal smoking or exposure to certain toxins can increase the risk.
• The recurrence risk for multifactorial disorders is higher in close relatives of affected individuals.

V. Diagnosis and Management

A. Genetic Testing

• Genetic testing plays a crucial role in the diagnosis and management of pediatric genetic disorders.
• Various techniques are used, including karyotyping, fluorescence in situ hybridization (FISH), and DNA sequencing.
• Genetic counseling is often recommended to discuss the implications of test results and provide guidance to families.

B. Symptomatic Management

• Treatment of pediatric genetic disorders focuses on managing symptoms and improving quality of life.
• Multidisciplinary approaches involving healthcare professionals from various specialties are often necessary.
• Supportive care, physical therapy, and medications are commonly used interventions.

C. Genetic Counseling and Family Planning

• Genetic counseling helps families understand the risk of recurrence and make informed decisions regarding family planning.
• Prenatal testing, such as chorionic villus sampling (CVS) and amniocentesis, can be