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Syndromic immunodeficiencies

Jeffrey E Ming, MD, PhD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Elizabeth TePas, MD, MS


A number of conditions featuring immunodeficiency may also present with clinical problems that are not directly due to the immunologic deficit (table 1) [1-4]. These conditions, termed "syndromic immunodeficiencies," are in contrast to primary immunodeficiencies, in which infection is the primary manifestation and the immune problem is well characterized. A large variety of manifestations have been described in the different syndromic immunodeficiencies, and a number of organ systems may be involved. Some of these conditions feature metabolic derangements or chromosomal anomalies.

Several genetic disorders may well be considered as both primary and syndromic immunodeficiencies since they have both characteristic organ dysfunction and/or dysmorphology unrelated to the immune system, as well as a consistent, well-defined immunodeficiency. Conditions such as Wiskott-Aldrich syndrome and ataxia-telangiectasia could be considered as fitting both categories and are discussed separately. (See "Wiskott-Aldrich syndrome" and "Ataxia-telangiectasia".)

Recognition of a syndromic immunodeficiency is important in several respects. For a patient with nonimmune-related anomalies who presents to the immunologist, it is critical to ascertain if the constellation of malformations is diagnostic for a specific syndrome. This may aid in giving an accurate prognosis for the immune defect. In addition, the diagnosis may alert the clinician to monitor for abnormalities in other organ systems. The prognosis for cognitive or motor development may also be impacted. Alternatively, if a child with one of these syndromes presents initially with nonimmune medical problems, then it is important to establish if an immune defect is present so that appropriate intervention can be undertaken. In addition, being able to establish the correct diagnosis may also have implications for the recurrence risk of future pregnancies of the patient or the patient's family and relatives.

In this topic review, we will focus on the more common syndromic immunodeficiencies in which immune defects are noted. A number of other syndromic immunodeficiencies are listed in the table (table 1). More complete delineation of syndromic immunodeficiencies, including rare conditions and those in which immune defects are only occasionally present, are available [1,2]. Some of these disorders are discussed in detail elsewhere. (See "Bloom syndrome" and "Nijmegen breakage syndrome".)


Cartilage-hair hypoplasia (CHH) is a rare, autosomal recessive form of short-limb dwarfism (metaphyseal chondrodysplasia). Associated features may include fine, sparse hair; cellular and humoral immunodeficiencies; Hirschsprung disease; hematologic and skin malignancies; autoimmune disease; and bronchiectasis. CHH is caused by defects in the ribonuclease mitochondrial RNA-processing (RMRP) gene. This disorder is discussed in detail separately. (See "Cartilage-hair hypoplasia".)

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Literature review current through: Nov 2017. | This topic last updated: Jul 25, 2017.
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