IllnessFanconi anemia, differential diagnosis

NGS +

[Sanger]

Fanconi anemia (FA) can affect many areas of the organism: Bone marrow insufficiency, physical and organ defects as well as increased risks for certain cancers. About 90% of FA patients have aplastic anemia with frequent infections due to neutropenia, thrombocytopenia, anemia, and may also develop a myelodysplastic syndrome. More than half of FA patients present with physical abnormalities such as hypopigmentation or café-au-lait spots. Other possible symptoms include malformed thumbs or forearms and additional skeletal problems including short stature, plus malformed or missing kidneys and other urinary tract defects, gastrointestinal abnormalities, heart defects, eye abnormalities such as small or specially shaped eyes and malformed ears with hearing loss. Patients may also have abnormal genitalia or other malformations of the reproductive system. Most affected males and about half of affected females are infertile. In addition, malformations of the central nervous system may be seen, including hydrocephalus or microcephaly. FA patients have an increased risk of developing acute myeloid leukemia or tumors of the head, neck, skin, gastrointestinal or genital tracts. The likelihood of developing one of these cancers ranges from 10-30%. Differential diagnosis often includes the pathophysiologically and clinically related autosomal recessive Bloom syndrome (incl. Bloom-like syndrome). FA is often inherited in an autosomal recessive, more rarely in dominant or X-linked recessive manner, but may also result from certain gene fusions. Although the vast majority of responsible mutations are detected when all known FA genes are included, very rare genetic abnormalities in additional genes are sometimes observed with similar clinical presentations. Also, a rare inconspicuous molecular genetic result does not exclude the clinical diagnosis with absolute certainty.

References: https://www.ncbi.nlm.nih.gov/books/NBK1401/

https://www.ncbi.nlm.nih.gov/books/NBK1398/

• Alias: Fanconi Pancytopenia
• Bloom syndrome (BLM)
• Fanconi anemia, complementation group A (FANCA)
• Fanconi anemia, complementation group B (FANCB)
• Fanconi anemia, complementation group D1 (BRCA2)
• Fanconi anemia, complementation group D2 (FANCD2)
• Fanconi anemia, complementation group E (FANCE)
• Fanconi anemia, complementation group F (FANCF)
• Fanconi anemia, complementation group G (FANCG)
• Fanconi anemia, complementation group I (FANCI)
• Fanconi anemia, complementation group J (BRIP1)
• Fanconi anemia, complementation group M (FANCM)
• Fanconi anemia, complementation group N (PALB2)
• Fanconi anemia, complementation group O (RAD51C)
• Fanconi anemia, complementation group P (SLX4)
• Fanconi anemia, complementation group Q (ERCC4)
• Fanconi anemia, complementation group R (RAD51)
• Fanconi anemia, complementation group S (BRCA1)
• Fanconi anemia, complementation group T (UBE2T)
• Fanconi anemia, complementation group U (XRCC2)
• Fanconi anemia, complementation group V (MAD2L2)
• Fanconi anemia, complementation group W (RFWD3)
• MGRISCE2 [Bloom-like syndrome] (TOP3A)