Infantile T-cell lymphopenia with or without nail dystrophy D81.4

"Infantile T-cell lymphopenia with or without nail dystrophy" (TLIND) is an autosomal dominant disorder characterized by decreased numbers of T cells, particularly CD8+ cytotoxic T cells, and usually occurs in infancy.

Bosticardo et al (2019) identified heterozygous mutations in the FOXN1 gene in 25 children and 22 adults with TLIND. Most of the mutations were nonsense, frameshift, or splice site mutations that resulted in loss of function. Du et al (2019) identified several children with heterozygous FOXN1 mutations with differentially reduced transcriptional activity.

Affected individuals tend to have an increased susceptibility to recurrent infections, especially respiratory viral infections. However, severity varies widely, and patients usually improve with age in childhood and adulthood, although CD8+ T cells remain decreased compared with normal.

Other features may include a small thymic shadow indicating impaired thymic development, skin manifestations (atopic dermatitis and nail dystrophies: koilonychia with significant thinning of the nail plate, canalicular nail dystrophy, transverse grooves in the nail plate(Beau-Reil's transverse grooves), leukonychia. In most patients, both finger and toe nails are affected.

Infection prophylaxis; bone marrow transplantation does not result in cure.

Patients are often identified by newborn screening, which detects low levels of TRECs.

1. Auricchio L et al (2005) Nail dystrophy associated with a heterozygous mutation of the nude/SCID human FOXN1 (WHN) gene. Arch Dermatol 2005141:647-648.
2. Bosticardo M et al (2019) Heterozygous FOXN1 variants cause low TRECs and severe T cell lymphopenia, revealing a crucial role of FOXN1 in supporting early thymopoiesis. Am J Hum Genet 105: 549-561.
3. Du Q et al (2019) FOXN1 compound heterozygous mutations cause selective thymic hypoplasia in humans. J Clin Invest 129: 4724-4738.
4. Pignata C et al.(1996) Congenital alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs. Am J Med Genet 65:167-170.