Congenital Disorders Overview

Congenital Disorders

• Affect approximately 4-8% of all births globally
• Higher rates in developing countries
• Occur due to a combination of genetic and environmental factors
• Genetic disorders arise from DNA alterations including deletions, mutations, and chromosomal abnormalities
• Environmental factors such as alcohol, smoking, infections, and nutrient deficiencies can increase the risk of birth defects
• The timing of susceptibility to environmental factors varies during embryonic development with early organs like the nervous system being most sensitive
• Prevention and management strategies include education about avoiding toxins and infections, improving maternal health, surgical interventions, and identifying genetic contributors
• Maternal supplementation with beneficial nutrients can reduce risks, such as folate to prevent neural tube defects

Disorders of Sexual Development (DSDs)

• Conditions where sex development is atypical, affecting chromosomes, genitals, or other body parts
• DSDs do not affect a person's identity
• Genetic changes in DSD individuals can alter sex chromosomes, hormone receptors, or enzymes
• This leads to a wide range of physical differences, sometimes making it hard to distinguish biological male from biological female
• Normally there are three stages of sex development: chromosomes, gonads, and genitals
• DSDs can cause mismatched or unclear genitalia and internal organs, causing uncertainty about male or female appearance
• Underlying causes of DSDs include:
  • Effecting the number of sex chromosomes
  • Mutating the function or expression of the sex-determining gene SRY
  • Affecting the sensitivity of sex hormone receptors
  • Altering the function of enzymes responsible for sex hormone synthesis

Turner Syndrome

• Individuals lack a full set of sex chromosomes (45 X,O), making them neither fully male nor female genetically
• More common than realized with 1/10 spontaneously aborted fetuses having this genetic makeup
• Results from chromosomal errors during meiosis
• Causes various symptoms such as short stature, physical features like webbed neck and broad chest, heart anomalies, and infertility
• Treatment involves growth hormone to increase height and hormone therapy to develop secondary sex characteristics and prevent issues like osteoporosis

Klinefelter's Syndrome

• A disorder where individuals inherit an extra X chromosome (47, XXY), making them genetically male but often displaying female secondary sex characteristics
• A common cause of male hypogonadism
• Symptoms include small testes, breast growth, reduced body hair, tall stature, and fertility issues
• Caused by non-disjunction of sex chromosomes during meiosis, particularly in females, and is linked to advanced maternal age
• Testicular dysgenesis leads to decreased testosterone production and increased estrogen, causing feminisation
• Diagnosis involves clinical assessment, hormone measurements, and karyotyping
• Treatment typically involves lifelong testosterone supplementation

Androgen Insensitivity Syndrome (AIS)

• A genetic disorder where genetically male individuals (46, XY) don't respond to male hormones due to mutations in the androgen receptor gene
• Causes feminisation of secondary sex characteristics and variable virilisation
• Complete AIS (CAIS) leads to externally female genitalia despite a Y chromosome, while partial AIS (PAIS) presents ambiguous genitalia
• Diagnosis involves hormone measurements and genetic testing
• Treatment depends on severity and includes estrogen replacement for CAIS and high-dose androgen therapy for PAIS
• Gonadectomy may be necessary to prevent malignancy in undescended testes
• AIS patients often require psychological support for gender identity challenges

Neural Tube Defects (NTDs)

• Relatively rare yet serious congenital malformations affecting the brain, spinal cord, or spine
• Impact 0.1% to 0.5% of global births
• Often tied to genetic mutations and predispositions, although improved understanding of environmental factors has reduced incidence
• Folic acid fortification, maternal health awareness, and advanced prenatal screening contribute to this reduction
• NTDs arise when neural tube closure goes awry, leading to severe conditions like anencephaly, iniencephaly, craniorachischisis, encephalocele, and spina bifida

This quiz explores congenital disorders affecting global births, emphasizing the influencing factors such as genetics and environment. It also touches on disorders of sexual development, their implications, and prevention strategies to improve maternal health. Test your knowledge on the prevalence and management of these conditions.