Typically results from a deletion in chromosome 22, which disrupts the development of the pharyngeal arches and pouches, and may also cause neurologic, immunologic, endocrinologic, or cognitive deficits.
Classic presentation is a triad of cardiac anomalies, hypoplastic thymus, and hypocalcemia, but clinical manifestations are highly variable, ranging from mild learning disabilities to the complete spectrum of congenital malformations. This phenotypic variability occurs despite a highly consistent genetic lesion.
Presenting signs and symptoms depend on age at diagnosis and the organ system affected. Knowledge of the particular characteristics for a given age helps guide follow-up and management.
Treatment modalities depend on clinical manifestations present in the individual patient. Management is symptomatic and generally follows typical practice for patients without the syndrome, for any given feature.
The classic presentation is a triad of cardiac anomalies, hypoplastic thymus, and hypocalcemia (resulting from parathyroid hypoplasia). 22q deletion syndrome (22qDS), described as DiGeorge syndrome or velocardiofacial syndrome, is the set of characteristic morphologic and neurologic features that result from the deletion of 1 copy of 22q11.2. The deletion causes a reduction in TBX1, a key transcription factor for development of the pharyngeal arches. This developmental disruption may cause cardiac anomalies, immunologic abnormalities, cleft lip and palate, hypoparathyroidism, learning disabilities, and schizophrenia. The disorder is notable for marked variation in the penetrance of the various features. The syndrome has been known by multiple other names, including CATCH22 and Shprintzen syndromes. The complexity of the nomenclature is due to great variability in the clinical syndrome.
The phenotype of DiGeorge syndrome may be divided into 2 components. The first, pharyngeal component consists of congenital heart disease, hypoplasia of the parathyroid glands, thymic hypoplasia with T-cell immunodeficiency, cleft lip and palate, and mild dysmorphic facial features. The second, neurologic phenotype consists of mild cognitive dysfunction, which typically presents as learning disabilities, speech impairment, and an increased incidence of schizophrenia.
History and exam
Sean A. McGhee, MD
Clinical Associate Professor
SAMG has provided testimony as an expert in a criminal case in which immune deficiency was a concern. SAMG is a co-author of a reference cited in this topic.
Maria Garcia Lloret, MD
David Geffen School of Medicine at UCLA
MGL is a co-author of a reference cited in this topic.
Gabriela M. Repetto, MD
Centro de Genetica Humana
Facultad de Medicina
Clínica Alemana-Universidad del Desarrollo
GMR is a co-author of a reference cited in this topic.
Lisa Kobrynski, MD, MPH
Associate Professor of Pediatrics
Division of Pulmonary, Allergy & Immunology, Cystic Fibrosis, and Sleep
LK is an investigator in clinical trials by Baxter Bioscience. These trials do not involve patients with 22q11DS. LK is an author of a number of references cited in this topic.
Winnie Ip, BHB, MBChB, FRACP, MD(Res)
Department of Immunology
Great Ormond Street Hospital
WI declares that she has no competing interests.
Use of this content is subject to our disclaimer