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T-cell immunodeficiency, congenital alopecia, and nail dystrophy(TIDAND)

MedGen UID:
355713
Concept ID:
C1866426
Disease or Syndrome
Synonyms: Alopecia and T-Cell Immunodeficiency; Congenital alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency; Pignata Guarino syndrome
SNOMED CT: Severe T-cell immunodeficiency, congenital alopecia, nail dystrophy syndrome (720345008); Alymphoid cystic thymic dysgenesis (720345008); Winged helix deficiency (720345008); Pignata Guarino syndrome (720345008); T-cell immunodeficiency, congenital alopecia, and nail dystrophy (720345008); Congenital alopecia and nail dystrophy with severe functional T-cell immunodeficiency (720345008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): FOXN1 (17q11.2)
 
Monarch Initiative: MONDO:0011132
OMIM®: 601705
Orphanet: ORPHA169095

Definition

T-cell immunodeficiency, congenital alopecia, and nail dystrophy (TIDAND) is an autosomal recessive primary immunodeficiency characterized by congenital thymic aplasia and severe T-cell immunodeficiency apparent at birth or soon thereafter. Affected individuals tend to have recurrent infections, oral candidiasis, and failure to thrive. Immunologic investigations show decreased numbers of T cells with poor proliferative response to phytohemagglutinin (PHA) and variable hypogammaglobulinemia. The phenotype is consistent with a T-/B+/NK+ form of severe combined immunodeficiency (SCID; see, e.g., 102700). Patients with FOXN1 mutations do not respond well to hematopoietic stem cell transplantation, as it is not curative; thymic transplantation offers a potential cure (Chou et al., 2014). [from OMIM]

Additional description

From MedlinePlus Genetics
T-cell immunodeficiency, congenital alopecia, and nail dystrophy is a type of severe combined immunodeficiency (SCID), which is a group of disorders characterized by an almost total lack of immune protection from foreign invaders such as bacteria and viruses. People with this form of SCID are missing functional immune cells called T cells, which normally recognize and attack foreign invaders to prevent infection. Without functional T cells, affected individuals develop repeated and persistent infections starting early in life. The infections result in slow growth and can be life-threatening; without effective treatment, most affected individuals live only into infancy or early childhood.

T-cell immunodeficiency, congenital alopecia, and nail dystrophy also affects growth of the hair and nails. Congenital alopecia refers to an absence of hair that is apparent from birth. Affected individuals have no scalp hair, eyebrows, or eyelashes. Nail dystrophy is a general term that describes malformed fingernails and toenails; in this condition, the nails are often ridged, pitted, or abnormally curved.

Researchers have described abnormalities of the brain and spinal cord (central nervous system) in at least two cases of this condition. However, it is not yet known whether central nervous system abnormalities are a common feature of T-cell immunodeficiency, congenital alopecia, and nail dystrophy.  https://medlineplus.gov/genetics/condition/t-cell-immunodeficiency-congenital-alopecia-and-nail-dystrophy

Clinical features

From HPO
T lymphocytopenia
MedGen UID:
419385
Concept ID:
C2931322
Finding
An abnormally low count of T cells.
Decreased helper T cell proportion
MedGen UID:
870281
Concept ID:
C4024723
Finding
Reduced proportion of helper T cells relative to the total number of T cells.
Severe T-cell immunodeficiency
MedGen UID:
870751
Concept ID:
C4025208
Disease or Syndrome
A primary immune deficiency that is characterized by defects or deficiencies of T-lymphocytes that causes specific susceptibility to intracellular micro-organisms.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Nail pits
MedGen UID:
57463
Concept ID:
C0150993
Finding
Small (typically about 1 mm or less in size) depressions on the dorsal nail surface.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Ridged nail
MedGen UID:
140853
Concept ID:
C0423820
Finding
Longitudinal, linear prominences in the nail plate.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVT-cell immunodeficiency, congenital alopecia, and nail dystrophy
Follow this link to review classifications for T-cell immunodeficiency, congenital alopecia, and nail dystrophy in Orphanet.

Recent clinical studies

Etiology

Pignata C, Fusco A, Amorosi S
Adv Exp Med Biol 2009;665:195-206. PMID: 20429426
Pignata C, Gaetaniello L, Masci AM, Frank J, Christiano A, Matrecano E, Racioppi L
Blood 2001 Feb 15;97(4):880-5. doi: 10.1182/blood.v97.4.880. PMID: 11159512

Diagnosis

Radha Rama Devi A, Panday NN, Naushad SM
Gene 2017 Sep 5;627:222-225. Epub 2017 Jun 19 doi: 10.1016/j.gene.2017.06.033. PMID: 28636882
Pignata C
J Hematother Stem Cell Res 2002 Apr;11(2):409-14. doi: 10.1089/152581602753658592. PMID: 11983112

Prognosis

Pignata C, Gaetaniello L, Masci AM, Frank J, Christiano A, Matrecano E, Racioppi L
Blood 2001 Feb 15;97(4):880-5. doi: 10.1182/blood.v97.4.880. PMID: 11159512

Clinical prediction guides

Pignata C, Fiore M, Guzzetta V, Castaldo A, Sebastio G, Porta F, Guarino A
Am J Med Genet 1996 Oct 16;65(2):167-70. doi: 10.1002/(SICI)1096-8628(19961016)65:2<167::AID-AJMG17>3.0.CO;2-O. PMID: 8911612

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