Information on TIDAND
Basic details
Name: T-cell immunodeficiency, congenital alopecia, and nail dystrophy | Acronym: TIDAND
Alt. names: Winged helix nude FOXN1 deficiency | Severe combined immunodeficiency due to FOXN1 deficiency
Gene: FOXN1 | MOI: Autosomal recessive | Mechanism of action: Loss of Function
No. of cases in DB: 16 | First reported in: 1999
Last updated on: 2023-04-01 03:29:42 by Xiao P. Peng
Description
Only 2 unrelated patients have been identified with this condition thus far (PMID: 31566583). Both were found to have undetectable TRECs on newborn screening – corresponding to typical T-B+NK+ severe combined immunodeficiency (SCID) in one patient, and a T-/loB+NK+ leaky SCID phenotype in the other. Patients showed defective thymopoiesis but without evidence of alopecia or nail dystrophy seen in the typical nude phenotype. The first infant succumbed to respiratory failure from recurrent early onset viral infections before age 1, but the other child received hematopoietic stem cell transplant at 6 months of age.
Management
Anti-microbial prophylaxis and early and aggressive treatment of infections may be beneficial. HSCT is unlikely to be curative for the thymus-intrinsic defect, but thymus transplant may be curative.
16 reported cases added to GenIA
| SubjectID | Sex | Fam.ID | AD | AFM | Validity | Country | Population | Reference & Pub.code |
|---|---|---|---|---|---|---|---|---|
102871 |
F | 215001 |
1 | 0 | Italy | Italian | PMID:8911612 [A.D.]; PMID:10206641 [Patient(II.2)]; PMID:33464451 [P1(II.2)]; PMID:28077132 [Fam.1:II.2(P1)] | |
| 102875 |
F | 215001 |
5 | 0 | Italy | Italian | PMID:8911612 [G.D.]; PMID:10206641 [Fam.Patient:II.3]; PMID:33464451 [Fam.P1:II.3(P2)]; PMID:28077132 [Fam.1:II.3(P2)]; PMID:11159512 [Patient] | |
| 102881 |
F | 215003 |
0 | 0 | Portugal | Portuguese | PMID:20978268 [Fam.1:II.1(P1)]; PMID:33464451 [P3]; PMID:28077132 [P7]; PMID:22590644 [Patient(II.1)] | |
| 102884 |
M | 215004 |
1 | 0 | Definitive | France | Admixed | PMID:20978268 [Fam.2:II.1(P2)]; PMID:33464451 [P4]; PMID:22721479 [Patient]; PMID:28077132 [P8] |
| 102887 |
F | 215005 |
1 | 0 | Lebanon | Lebanese | PMID:25173801 [Patient(II.1)]; PMID:33464451 [P5]; PMID:28077132 [P9] | |
| 102891 |
F | 215006 |
0 | 0 | India | Indian | PMID:28636882 [Patient(II.3)]; PMID:33464451 [P6] | |
| 102894 |
M | 215006 |
1 | 0 | India | Indian | PMID:28636882 [Fam.Patient:II.2]; PMID:33464451 [P7] | |
| 102897 |
M | 215007 |
0 | 0 | Turkey | Turkish | PMID:30903456 [P1(II.1)]; PMID:33464451 [P12(II.1)]; PMID:37419334 [P12(27)] | |
| 102900 |
F | 215007 |
1 | Turkey | Turkish | PMID:30903456 [Fam.P1:II.2(P2)]; PMID:33464451 [Fam.P12:II.2(P13)]; PMID:37419334 [P13(27)] | ||
| 102901 |
F | 215008 |
0 | 0 | Brazil | Brasilian | PMID:35064468 [patient(II.2)] | |
| 102905 |
F | 215009 |
0 | -1 | Italy | Italian | PMID:20864124 [Fam.Fetus:II.1(Fetus 1)]; PMID:18339010 [Fetus(II.1)] | |
| 102910 |
U | 215009 |
0 | -1 | Italy | Italian | PMID:20864124 [Fam.Fetus:II.2(Fetus 2)] | |
| 102959 |
U | 215057 |
0 | -1 | Italy | Italian | PMID:21507891 [Patient(II.1)] | |
| 106144 |
F | 215953 | 0 | Definitive | Italy | Italian | PMID:33464451 [P8]; PMID:37419334 [P8(27)] | |
| 106145 |
M | 215954 | 12 | 2 | Definitive | Slovakia | Slovak | PMID:33464451 [P9]; PMID:37419334 [P9(27)] |
| 106150 |
F | 215955 | 4 | 0 | Definitive | Turkey | Turkish | PMID:33464451 [P10] |
AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).
Summary of clinical findings
[Considering only Definitive and Possible cases]
| Rank | Clinical term | Present | Absent | Unreported |
|---|---|---|---|---|
| 1 | Thymus aplasia |
12 (75.0%) | 0 (0.0%) | 4 (25.0%) |
| 2 | Reduced T cell count |
10 (62.5%) | 0 (0.0%) | 6 (37.5%) |
| 3 | Nail dystrophy |
10 (62.5%) | 2 (12.5%) | 4 (25.0%) |
| 4 | (unusual) Respiratory tract infection |
9 (56.3%) | 3 (18.8%) | 4 (25.0%) |
| 5 | Lung disease |
9 (56.3%) | 3 (18.8%) | 4 (25.0%) |
| 6 | Pneumonia |
9 (56.3%) | 3 (18.8%) | 4 (25.0%) |
| 7 | Enteropathy |
8 (50.0%) | 4 (25.0%) | 4 (25.0%) |
| 8 | Diarrhea |
8 (50.0%) | 4 (25.0%) | 4 (25.0%) |
| 9 | Erythroderma |
7 (43.8%) | 5 (31.3%) | 4 (25.0%) |
| 10 | Alopecia totalis |
6 (37.5%) | 0 (0.0%) | 10 (62.5%) |
| 11 | Epicanthus |
5 (31.3%) | 7 (43.8%) | 4 (25.0%) |
| 12 | Absent eyelashes |
4 (25.0%) | 0 (0.0%) | 12 (75.0%) |
| 13 | Lymphadenopathy |
4 (25.0%) | 0 (0.0%) | 12 (75.0%) |
| 14 | Mucocutaneous candidiasis |
4 (25.0%) | 0 (0.0%) | 12 (75.0%) |
| 15 | Absent eyebrow |
4 (25.0%) | 0 (0.0%) | 12 (75.0%) |
| 16 | Abnormal lymphoproliferation |
4 (25.0%) | 0 (0.0%) | 12 (75.0%) |
| 17 | Alopecia |
4 (25.0%) | 0 (0.0%) | 12 (75.0%) |
| 18 | Oral candidiasis |
4 (25.0%) | 0 (0.0%) | 12 (75.0%) |
| 19 | Eosinophilia |
3 (18.8%) | 1 (6.3%) | 12 (75.0%) |
| 20 | Lymphopenia |
3 (18.8%) | 0 (0.0%) | 13 (81.3%) |
| 21 | Reduced number of B cells |
3 (18.8%) | 2 (12.5%) | 11 (68.8%) |
| 22 | Severe T-cell immunodeficiency |
3 (18.8%) | 0 (0.0%) | 13 (81.3%) |
| 23 | Failure to thrive |
3 (18.8%) | 9 (56.3%) | 4 (25.0%) |
| 24 | Hypogammaglobulinemia |
3 (18.8%) | 1 (6.3%) | 12 (75.0%) |
| 25 | (unusual) Viral infection |
3 (18.8%) | 1 (6.3%) | 12 (75.0%) |
| 26 | Decreased IgG levels |
2 (12.5%) | 1 (6.3%) | 13 (81.3%) |
| 27 | Hematopoietic stem cell transplantation |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 28 | Reduced NK cell number |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 29 | Thrombocytopenia |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 30 | Hepatopathy |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 31 | Thymus transplantation |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 32 | Hepatosplenomegaly |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 33 | Decreased IgM levels |
2 (12.5%) | 1 (6.3%) | 13 (81.3%) |
| 34 | Autoimmunity |
2 (12.5%) | 10 (62.5%) | 4 (25.0%) |
| 35 | Alopecia of scalp |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 36 | Reduced proportion of CD8 T cells |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 37 | Increased IgE levels |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 38 | (Unusual) bacterial infection |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 39 | Impaired T cell function |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 40 | Cytomegalovirus infection |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 41 | Unusual infection |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 42 | Reduced proportion of naive T cells |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 43 | Increased NK cell number |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 44 | BCGitis |
2 (12.5%) | 0 (0.0%) | 14 (87.5%) |
| 45 | Decreased IgA levels |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 46 | Otitis media |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 47 | Hypothyroidism |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 48 | Anti-thyroglobulin antibody positivity |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 49 | Recurrent lower respiratory tract infections |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 50 | Gastrointestinal inflammation |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 51 | B-cell lymphoma |
1 (6.3%) | 10 (62.5%) | 5 (31.3%) |
| 52 | Neural tube defect |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 53 | Pneumocystis jiroveci pneumonia |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 54 | Decreased proportion of CD3-positive T cells |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 55 | Petechiae |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 56 | Hypopigmented skin patches |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 57 | Septicaemia |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 58 | repeated bacterial infections |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 59 | Abnormal corpus callosum morphology |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 60 | Anencephaly |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 61 | Spina bifida |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 62 | Increased number of B cells |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 63 | Decreased IgE levels |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 64 | Lymphadenitis |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 65 | Endocrine system abnormality |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 66 | Neutropenia |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 67 | Skin abnormality |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 68 | Acute kidney failure |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 69 | Anemia |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 70 | Herpes Simplex Virus Infection |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 71 | (unusual) Epstein-Barr virus infection |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 72 | Nontuberculous mycobacterial pulmonary infection |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 73 | Urticaria |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 74 | Alopecia universalis |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 75 | Growth delay |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 76 | Hypergammaglobulinaemia |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 77 | Respiratory failure |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 78 | Varicella zoster virus infection |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 79 | Non-Hodgkin lymphoma |
1 (6.3%) | 10 (62.5%) | 5 (31.3%) |
| 80 | Generalized lymphadenopathy |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 81 | Rotavirus infection |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 82 | Autoimmune antibody positivity |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 83 | Skin rash |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 84 | Reduced proportion of CD4 T cells |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 85 | BCGosis |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 86 | Respiratory distress |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 87 | anti-TPO antibodies |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 88 | Dermatographic urticaria |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 89 | Hypoxemia |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 90 | Cytomegalovirus Infection Reactivation |
1 (6.3%) | 0 (0.0%) | 15 (93.8%) |
| 91 | Oral leukoplakia |
0 (0.0%) | 1 (6.3%) | 15 (93.8%) |
Summary of treatment outcomes
[Considering only Definitive and Possible cases]
| Treatment ⓘ | Responses & clinical indications |
|---|---|
| Antihistamines | Moderate (1) for Urticaria |
| Biological agents | Excelent/Remision (1) for (unusual) Epstein-Barr virus infection |
| Monoclonal antibodies | Excelent/Remision (1) for (unusual) Epstein-Barr virus infection |
| Rituximab | Excelent/Remision (1) for (unusual) Epstein-Barr virus infection |
| Surgery | Good (2) for Thymus aplasia. Excelent/Remision (2) for Thymus aplasia. Negative/Bad (1) for Thymus aplasia |
| Levothyroxine | Good (1) for Hypothyroidism |
| Hematopoietic stem cell transplantation | Negative/Bad (2) for Reduced T cell count; unspecified. Unspecified (2) for unspecified. Good (1) for unspecified |
| Chemotherapy | Excelent/Remision (1) for B-cell lymphoma |
| Thymus transplantation | Good (2) for Thymus aplasia. Excelent/Remision (2) for Thymus aplasia. Negative/Bad (1) for Thymus aplasia |