These consist of several groups of PIDs(1).

DNA repair defects may lead to PIDs characterized by radiosensitivity, DNA damage and increased risk for malignancy (2) such as ataxia-telangiectasia (A-T)(3), Nijmegen breakage syndrome(4) and Bloom syndrome(5). Clinically, AT presents with uncoordinated or ataxic movements that are often associated with ocular telangiectasia (dilated blood vessels of the eye). Due to the neurological impairment individuals are usually wheelchair-bound early in life (6).

Immune-osseous dysplasias,(7,8) consist of PIDs associated with abnormalaties of the skeletal system. Cartilage Hair Hypoplasia (CHH) patients are characterized by short limb dwarfism and bowing of the legs with very short and hyperextensible fingers. Hair is fine and sparse. The degree of immunodeficiency is variable with a striking tendency for fatal disseminated varicella or EBV driven lymphoma (9). Schimke immune osseous dysplasia is characterized by short stature, hyperpigmented macules, low lymphocyte levels and kidney failure(10).

Thymic disorders result in DiGeorge anomaly(11,12). The most frequent clinical features include heart defects, palatal abnormalities (e.g. cleft palate), low calcium levels and characteristic facial features(13). Less than 1% of these have no detectable thymus and are classified as "complete" DiGeorge anomaly(14). Those with a "complete" DiGeorge are at risk for opportunistic infections such as Pneumocystis jiroveci and Cytomegalovirus. Live viral vaccines (e.g. MMR vaccine) should be avoided in DiGeorge patients with low T-cell numbers or impaired T-cell function(15). Thymus transplantation is a promising investigational therapy for infants born with no thymus(16).

Wiskott-Aldrich syndrome (WAS) is a PID associated with microthrombocytopenia (low levels of small platelets), bloody diarrhea, eczema, recurrent infections, and a high incidence of malignancies (17). The success of hematopoietic stem cell transplantation in WAS patients is related to the recipient's age, donor selection, the conditioning regimen and the extent of reconstitution(18)

The Hyper-IgE syndrome is characterized by the classic triad of recurrent skin boils, cyst-forming pneumonias, and extreme elevations of serum IgE. Other common manifestations include eczema, cutaneus fungal infections, and skeletal abnormalities (19-21). The major risk is Gram-negative (Pseudomonas) bacterial or fungal lung infection. Treatment consists mainly of prevention of staphylococcal skin abscesses and pneumonias with anti-staphylococcal prophylactic antibiotics and prompt aggressive treatment of infections. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutation in the family is known(21).

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2. Nahas SA, Gatti RA. DNA double strand break repair defects, primary immunodeficiency disorders, and 'radiosensitivity'. Curr Opin Allergy Clin Immunol 2009;9:510-516.

3. Lavin MF. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 2008;9:759-769.

4. Kondratenko I, Paschenko O, Polyakov A, Bologov A. Nijmegen breakage syndrome. Adv Exp Med Biol 2007;601:61-67.

5. Kaneko H, Kondo N. Clinical features of Bloom syndrome and function of the causative gene, BLM helicase. Expert Rev Mol Diagn 2004;4:393-401.

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7. Rider NL, Morton DH, Puffenberger E, Hendrickson CL, Robinson DL, Strauss KA. Immunologic and clinical features of 25 Amish patients with RMRP 70 A--G cartilage hair hypoplasia. Clin Immunol 2009;131:119-128.

8. Baradaran-Heravi A, Thiel C, Rauch A, Zenker M, Boerkoel CF, Kaitila I. Clinical and genetic distinction of Schimke immuno-osseous dysplasia and cartilage-hair hypoplasia. Am J Med Genet A 2008;146A:2013-2017.

9. Notarangelo LD, Roifman CM, Giliani S. Cartilage-hair hypoplasia: molecular basis and heterogeneity of the immunological phenotype. Curr Opin Allergy Clin Immunol 2008;8:534-539.

10. Boerkoel CF, O'Neill S, Andre JL, Benke PJ, Bogdanovic R, Bulla M et al. Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature. Eur J Pediatr 2000;159:1-7.

11. Shprintzen RJ. Velo-cardio-facial syndrome: 30 Years of study. Dev Disabil Res Rev 2008;14:3-10.

12. Sullivan KE. DiGeorge syndrome/velocardiofacial syndrome: the chromosome 22q11.2 deletion syndrome. Adv Exp Med Biol 2007;601:37-49.

13. Fernandez L, Nevado J, Santos F, Heine-Suner D, Martinez-Glez V, Garcia-Minaur S et al. A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review. BMC Med Genet 2009;10:48.

14. Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE et al. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood 2007;109:4539-4547.

15. Kobrynski LJ, Sullivan KE. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 2007;370:1443-1452.

16. Markert ML, Devlin BH, McCarthy EA. Thymus transplantation. Clin Immunol 2010;135:236-246.

17. Rengan R, Ochs HD. Molecular biology of the Wiskott-Aldrich syndrome. Rev Immunogenet 2000;2:243-255.

18. Notarangelo LD, Miao CH, Ochs HD. Wiskott-Aldrich syndrome. Curr Opin Hematol 2008;15:30-36.

19. Ozcan E, Notarangelo LD, Geha RS. Primary immune deficiencies with aberrant IgE production. J Allergy Clin Immunol 2008;122:1054-1062.

20. Ochs HD, Oukka M, Torgerson TR. TH17 cells and regulatory T cells in primary immunodeficiency diseases. J Allergy Clin Immunol 2009;123:977-983.

21. Freeman AF, Davis J, Hsu AP, Holland SM, Puck JM. Autosomal Dominant Hyper IgE Syndrome. 1993.