What diseases are caused by genetic or chromosomal abnormalities, such as Sickle Cell Disease (SCD), Autism Spectrum Disorder (ASD), Marfan Syndrome, and Hyperhidrosis (HH)?

Diseases Caused by Genetic or Chromosomal Abnormalities

Among the options listed, sickle cell disease, autism spectrum disorder, and Marfan syndrome are all caused by genetic or chromosomal abnormalities, while halitosis (bad breath) is not a genetic disorder.

Sickle Cell Disease (Option A)

• Sickle cell disease is definitively caused by a genetic mutation in the gene responsible for producing hemoglobin, specifically resulting in abnormal hemoglobin S 1, 2.
• This is an inherited disorder of hemoglobin characterized by formation of long chains of hemoglobin when deoxygenated, resulting in sickle-shaped red blood cells 1.
• The mutation causes red blood cells to become stiff and sticky, leading to vaso-occlusion with associated ischemia and progressive multiorgan damage 1.
• SCD is a hereditary blood disorder that follows an autosomal recessive inheritance pattern 2.

Autism Spectrum Disorder (Option B)

• Chromosomal abnormalities have consistently been reported in persons with ASDs, with conventional cytogenetic studies yielding approximately 3% diagnostic rate 3.
• Chromosomal microarray analysis identifies copy number variants in 8-21% of individuals with ASD, with cumulative studies finding 10% of patients with clinically significant CNVs 3.
• Multiple specific genetic causes have been identified, including Fragile X syndrome, MECP2 gene mutations, and PTEN gene mutations 3.
• Defined mutations, genetic syndromes, and metabolic diseases account for up to 20% of autistic patients 4.
• The rate of success for identifying a specific etiologic diagnosis in persons with ASDs ranges from 6-15%, with newer testing modalities potentially achieving 30-40% diagnostic yield 3.
• Twin studies demonstrate 60% concordance for classic autism in monozygotic twins versus 0% in dizygotic twins, with concordance increasing to 92% in MZ twins when broader autistic phenotypes are considered 5.
• Whole-genome screens suggest interactions of at least 10 genes in the causation of autism, with the 7q31-q33 region most strongly linked 5.

Marfan Syndrome (Option C)

• Marfan syndrome is an autosomal dominant inherited connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene 3, 6.
• The disorder is characterized by variable clinical manifestations in the cardiovascular, musculoskeletal, and ocular systems due to defective fibrillin-1 protein affecting connective tissue integrity 7, 6.
• All conditions related to Marfan syndrome (except arterial tortuosity syndrome, which is recessive) can be inherited as autosomal dominant traits 3.
• Missense mutations in FBN1 show the highest correlation with specific phenotypic expressions, with approximately 70% probability of presence in certain phenotype classes 6.

Halitosis (Option D) - NOT a Genetic Disorder

• Halitosis (bad breath) is not caused by genetic or chromosomal abnormalities and does not appear in any genetic disease literature.
• This condition results from oral hygiene issues, dental problems, dietary factors, or systemic conditions—none of which are genetic disorders.

Clinical Implications

• For sickle cell disease, diagnosis occurs through newborn screening programs where available, or when patients present with unexplained severe atraumatic pain or normocytic anemia 1.
• For autism spectrum disorders, a genetic evaluation should be offered to every person with an ASD because identifying a specific etiology allows for specific recurrence-risk counseling and targeted testing of at-risk family members 3.
• For Marfan syndrome, echocardiography is essential whenever the condition is seriously considered, and slit-lamp examination with fully dilated pupils is essential to exclude ectopia lentis 3.