Diamond-Blackfan Syndrome, family history of

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The following guidance was received from Dr Adrianna Vlachos (Head, Bone Marrow Failure Program, Steven and Alexandra Cohen Children's Medical Center of New York Hematology/Oncology and Stem Cell Transplantation Feinstein Institute for Medical Research):


Dear Dr. Lown

These are very interesting questions. We know that DBA is found to be inherited as an autosomal dominant in ~45% of RPS19 cases, with parents and other family members often showing mild or no signs of anemia. This was published years ago by Dr. Orfali and Dr. Ball from the UK DBA data.

All of the RPS and RPL mutations known to date are wither auto dominant or new sporadic mutations. Gata1 is inherited as X-linked.

We do recommend that persons with an affected family member be screened with a CBC and erythrocyte ADA activity, and take particular interest if there are family members with congenital anomalies. If a genetic mutation is found in the proband then we do offer genetic testing on the immediate family members.

There was an abstract years ago of a child (age 10) who was a donor for her younger brother with DBA. She was clinically well. Unfortunately the BM did not engraft and 3 years later, at her puberty, the donor presented with anemia and was found to have an elevated eADA.

Having said this, your questions pose an interesting discussion. We of course would not screen the general population for any of these autosomal dominant disorders in a standard way. However if the donor had an affected child and a mutation was known on that child then she should be screened for the same mutation, even if her CBC and eADA were normal. We identify family members all the time in our screening that have the mutation and are "silent" at this time. We don't know what they will do in the future - as we have had patients present as adults. Most importantly, we believe that this bone marrow would probably not engraft well into the patient.

If the mother is negative for the mutation her child has, then there is a small chance of gonadal mosaicism but this would not affect her being a BM donor.

If she was positive I would not count her as a BM donor.

If there is no gene identified then the CBC and eADA could be used as screening tools. If no anemia, macrocytosis or elevated eADA then the accepting physician could make the call about using the donor, especially if this was the only one for that patient.