NLRP1

Autoinflammation with Arthritis and Dyskeratosis

Clinical Characteristics
Ocular Features: 

Signs and symptoms of dry eyes are evident early in the first decade.  Punctate keratitis with photophobia are present by 5 or 6 years of age followed by corneal dyskeratosis and neovascularization.  One 16-year-old male was reported to have uveitis.

Systemic Features: 

Recurrent febrile episodes lasting 3-4 days with impaired sweating occur early in the first decade.  Small hyperkeratosis may be seen on the limbs, shoulders, and flanks.  Diffuse xerosis is evident throughout.  Keratotic lesions occur on the soles as well.   Arthritis in the lower limbs occurs by the beginning of the second decade or earlier.  Metaphyseal striations and irregular condensations may be seen in the distal femora and proximal tibial bones.

Hypereosinophilia with elevated IgE and IgA levels and reduced vitamins A and C have been reported.  Immune hemolytic anemia, thyroiditis, and abnormal B-cell profiles may be present.

Genetics

Heterozygous and homozygous mutations in the NLRP1 gene (17p13) have been associated with this condition in several families.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment has been reported.

References
Article Title: 

A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis)

Grandemange S, Sanchez E, Louis-Plence P, Tran Mau-Them F, Bessis D, Coubes C, Frouin E, Seyger M, Girard M, Puechberty J, Costes V, Rodiere M, Carbasse A, Jeziorski E, Portales P, Sarrabay G, Mondain M, Jorgensen C, Apparailly F, Hoppenreijs E, Touitou I, Genevieve D. A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis). Ann Rheum Dis. 2016 Dec 13. pii: annrheumdis-2016-210021. doi: 10.1136/annrheumdis-2016-210021.

PubMed ID: 
27965258

Dyskeratosis, Hereditary Benign Intraepithelial

Clinical Characteristics
Ocular Features: 

The conjunctival surface has elevated, granular-appearing white epithelial plaques usually in the interpalpebral areas.  These may extend onto the cornea and cause interference with vision.  The plaques may also shed spontaneously.  The lesions may have prominent blood vessels with associated conjunctival hyperemia with considerable cosmetic implications.

The plaque-like growths remain localized and do not invade tissue.  The surface epithelium is hyperkeratotic with acanthosis and individual cell dyskeratoses.

Systemic Features: 

The oral and lingual mucosa may also be involved.

Genetics

A segment of DNA localized at 4q35 is duplicated resulting in triple alleles for 2 linked markers suggesting that gene duplication is responsible for the disorder.  It occurs almost exclusively among members of a triracial isolate (Haliwa Indians) in North Carolina.

Families with autosomal dominant transmission have been reported.  In one French Canadian family in which mother and son were affected a nonsense mutation in NLRP1 (17p13.2) was found.  This may be a unique disorder.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Local excision as needed.

References
Article Title: 

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis

Soler VJ, Tran-Viet KN, Galiacy SD, Limviphuvadh V, Klemm TP, St Germain E, Fourni?(c) PR, Guillaud C, Maurer-Stroh S, Hawthorne F, Suarez C, Kantelip B, Afshari NA, Creveaux I, Luo X, Meng W, Calvas P, Cassagne M, Arne JL, Rozen SG, Malecaze F, Young TL. Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis. J Med Genet. 2013 Jan 24. [Epub ahead of print].

PubMed ID: 
23349227
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