Congenital athymia

[galyea123]

Hi! I am currently working on updating a NORD report in what is called "congenital athymia" and I did not find this listed as it in Orphanet and started reviewing the related conditions to thymus anomalies in Orphanet.

The group "immunodeficiency due to absence of thymus" could be a synonym for congenital athymia but I found some other issues.

Both "Immunodeficiency due to absence of thymus" ORPHA:331220 (which includes 22q11.2 deletion syndrome ORPHA:567 CHARGE syndrome ORPHA:138 and T-cell immunodeficiency with thymic aplasia (Nezelof syndrome) ORPHA:83471) and "Severe combined immunodeficiency due to FOXN1 deficiency" are currently classified under "Syndrome with combined immunodeficiency"ORPHA:331217, but the immunodeficiency due to FOXN1 deficiency is listed separately and not under absent thymus:

• Primary immunodeficiency due to a defect in adaptive immunity ORPHA:179006 o Syndrome with combined immunodeficiency ORPHA:331217 o Absent thumb-short stature-immunodeficiency syndrome ORPHA:2951 o Anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome ORPHA:69088 o Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis ORPHA:329173 o Combined immunodeficiency due to CRAC channel dysfunction ORPHA:169090 o Combined immunodeficiency-enteropathy spectrum ORPHA:436252 o Developmental delay-immunodeficiency-leukoencephalopathy-hypohomocysteinemia syndrome ORPHA:619979 o DNA repair defect other than combined T-cell and B-cell immunodeficiencies ORPHA:169346 o Dyskeratosis congenita ORPHA:1775 o Facial dysmorphism-immunodeficiency-livedo-short stature syndrome ORPHA:352712 o Hennekam syndrome ORPHA:2136 o Hepatic veno-occlusive disease-immunodeficiency syndrome ORPHA:79124 o Hereditary folate malabsorption ORPHA:90045 o Hoyeraal-Hreidarsson syndrome ORPHA:3322 o Hyper-IgE syndrome ORPHA:331223 o Hypohidrotic ectodermal dysplasia with immunodeficiency ORPHA:98813 o Immunodeficiency due to absence of thymus ORPHA:331220  22q11.2 deletion syndrome ORPHA:567  CHARGE syndrome ORPHA:138  T-cell immunodeficiency with thymic aplasia ORPHA:83471 o Immuno-osseous dysplasia ORPHA:169349 o Laron syndrome with immunodeficiency ORPHA:220465 o Multiple intestinal atresia ORPHA:2300 o Pancytopenia due to IKZF1 mutations ORPHA:317473 o Severe combined immunodeficiency due to FOXN1 deficiency ORPHA:169095 o Transcobalamin deficiency ORPHA:859 o Vici syndrome ORPHA:1493 o Wiskott-Aldrich syndrome ORPHA:906

It is my understanding that the condition "T-cell immunodeficiency with thymic aplasia" is caused by compound heterozygous mutations in the FOXN1 (see OMIM and also a review:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249278/

My doubts are:

• this condition "T-cell immunodeficiency with thymic aplasia" is, in fact, part of the FOXN1 deficiency
• FOXN1 deficiency should be classified under Immunodeficiency due to absence of thymus
• Can immunodeficiency due to absence of thymus be considered a synonym of congenital athymia?

Note that for congenital athymia there is plenty of literature and also an FDA approved treatment.

I appreciate your help on this! Thank you very much! Gioconda Alyea

[MCecile-US14]

Dear @caterina-lucano-orphanet,

As this concern clarifications and classification issue, could you please take a look at this request when you have time?

Thank you, Kind regards, Marie-Cécile

[Orphanet-AysegulSenol]

Dear Gioconda,

I am sorry for this late update but I am currently working on your request and I hope I will be able to give you a detailed answer in a short time. Meanwhile, I was wondering whether it would be possible for you to provide a source for the information that I found in NORD page which says congenital athymia can occur as an "isolated" finding (in addition to being a part of a genetic syndrome). It would be great to have some information on these isolated cases.

Thank you very much in advance,

Best wishes,

Aysegul

[galyea123]

Hi Aysegul! I believe that the report was referring to T-cell immunodeficiency with thymic aplasia. I will make some changes to the NORD report so this is more clear. Thank you, Gioconda