SNP Shot: Genomic Insights

Fanconi anemia is a complex disorder impacting multiple body systems. Individuals with this condition may experience bone marrow failure, have physical differences, exhibit organ defects, and face a higher chance of developing certain cancers.

Bone marrow's primary job is to create new blood cells: red blood cells (carrying oxygen), white blood cells (fighting infection), and platelets (enabling blood clotting). Roughly 90% of those with Fanconi anemia suffer from impaired bone marrow function, leading to aplastic anemia – a reduction in all blood cell types. This results in extreme fatigue (from anemia/low red blood cell count), frequent infections (from neutropenia/low white blood cell count), and clotting problems (from thrombocytopenia/low platelet count). Furthermore, individuals with Fanconi anemia can develop myelodysplastic syndrome, where immature blood cells don't mature properly.

More than half of individuals with Fanconi anemia display physical abnormalities. These can include skin pigmentation issues like unusually light skin (hypopigmentation) or café-au-lait spots (flat, darker patches). Other possible features include malformed thumbs or forearms, other skeletal problems like short stature, kidney and urinary tract defects, gastrointestinal abnormalities, heart defects, eye abnormalities (e.g., small or abnormally shaped eyes), and malformed ears and hearing loss. Genital and reproductive system malformations can occur, leading to infertility in most affected males and roughly half of affected females. Less common signs and symptoms can involve the brain and spinal cord (central nervous system), such as increased fluid in the brain (hydrocephalus) or an unusually small head (microcephaly).

Individuals with Fanconi anemia have a greater risk of developing acute myeloid leukemia (AML), a cancer of the blood-forming cells in the bone marrow, or tumors affecting the head, neck, skin, gastrointestinal system, or genital tract. The probability of developing one of these cancers in individuals with Fanconi anemia ranges from 10% to 30%.

Inheritance:

Fanconi anemia is most often inherited in an autosomal recessive manner. This means that both copies of the responsible gene in each cell must carry a mutation for the condition to manifest. Parents of an individual with an autosomal recessive condition each carry one mutated gene copy but usually do not display any signs or symptoms themselves.

In rare cases, the condition follows an X-linked recessive inheritance pattern. The relevant gene for X-linked Fanconi anemia resides on the X chromosome, one of the two sex chromosomes. Males (possessing only one X chromosome) only require one altered gene copy in each cell to be affected. Females (with two X chromosomes) would need a mutation in both gene copies for the disorder to develop. Due to the lower likelihood of females having two altered copies of the gene, X-linked recessive disorders affect males considerably more often than females. Notably, fathers cannot pass X-linked traits onto their sons.