Congenital athymia's clinical symptoms are directly related to the thymus's absence and its incapacity to generate
T cells with the necessary immune capabilities. An increased vulnerability to bacterial, viral, and fungal infections results from
T-cellimmunodeficiency.[1]
Congenital athymia is linked to a number of
genetic disorders, congenital syndromes, and environmental variables. Genetic abnormalities that are either (1) unique to the development of the thymic organ or (2) related to the development of the midline region as a whole can cause congenital athymia.[1]
Risk factors
Congenital athymia is linked to multiple environmental etiologies. Affected fetal thymus size and other congenital anomalies like
renal agenesis and
butterfly vertebrae are linked to
diabetic embryopathy.[9] It has been shown that babies of diabetic mothers have thymic aplasia.[10]Retinoic acid exposure during fetal development is also linked to phenotypes associated with
DiGeorge syndrome, such as hypoplasia and thymic developmental abnormalities such as aplasia and ectopia.[11]
Genetics
The most well-known gene associated with thymic development is Forkhead Box N1 (
FOXN1). As a member of the transcription factor family known as the forkhead box gene family,
FOXN1 plays a role in the growth and differentiation of skin
epithelial cells as well as the development, differentiation, and maintenance of
thymic epithelial cells during embryonic and postnatal life.[12][13][14]
The
transcription factors known as the paired box family, which control tissue differentiation, includes Paired Box 1 (
PAX1).[15] Numerous studies have reported on patients with autosomal recessive
otofaciocervical syndrome type 2 (OTFCS2) and mutations in
PAX1. Because of altered thymus development, OTFCS2 is associated with a syndromic form of
SCID.[16][17]
The two most common genetic syndromes linked to thymus development defects are
22q11.2 deletion syndrome and
CHARGE syndrome. Patients with these syndromes exhibit a variety of symptoms because the genes
TBX1 and
CHD7, which are linked to these specific disorders, are involved in the development of the entire midline region.[1] Additional genes that may be involved in healthy thymus development are
FOXI3 and
TBX2.[18][19]
Treatment
In October 2021, the thymus tissue product
Rethymic was approved by U.S.
Food and Drug Administration (FDA) as a
medical therapy for the treatment of children with congenital athymia.[20] It takes six months or longer to reconstitute the immune function in treated children.[20]
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