The 22q11.2 Deletion Syndrome (22q11DS) is the most common chromosomal microdeletion disorder, characterised by a heterogeneous clinical spectrum including immunodeficiency, autoimmunity, and neuropsychiatric comorbidities. This systematic review critically appraises current evidence on autoimmunity in 22q11DS, fulfilling the need for an unbiased and comprehensive synthesis of the current literature.

An extensive search was conducted through PubMed, Web of Science, EMBASE, CINAHL, and the Cochrane Library using Boolean combinations of relevant keywords. Qualitative studies, abstracts, conference proceedings and non-English studies were excluded.

A total of 82 peer-reviewed studies published since 1968 were identified. We identified a total of 40 distinct autoimmune conditions involving multiple organ systems. Haematological disorders were most frequently cited, followed by autoimmune thyroid diseases and systemic autoimmune diseases. Less common conditions included coeliac disease, psoriasis, vitiligo, alopecia areata, Raynaud’s phenomenon, and vasculitis, while 19 diseases appeared only as single-case reports. Neuropsychiatric manifestations were addressed in 24 studies.

Our review confirms that autoimmunity is a complication of 22q11DS and highlights the need for epidemiological studies across organ-systems and inclusion of ethnically diverse populations. There was substantial variation in study designs, underscoring the need for more standardised approaches and larger sample sizes.

CHD is an important phenotypic feature of chromosome 22q11.2 copy number variants. Biventricular repair is usually possible, however there are rare reports of patients with chromosome 22q copy number variants and functional single ventricle cardiac disease.

This is a single centre retrospective review of patients with chromosome 22q copy number variants who underwent staged single ventricle reconstructive surgery between 1 July, 1984 and 31 December, 2020.

Seventeen patients met inclusion criteria. The most common diagnosis was hypoplastic left heart syndrome (n = 8) and vascular anomalies were present in 13 patients. A microdeletion of the chromosome 22 A-D low-copy repeat was present in 13 patients, and the remaining had a duplication. About half of the patients had documented craniofacial abnormalities and/or hypocalcaemia, and developmental delay was very common. Fifteen patients had a Norwood operation, 10 patients had a superior cavopulmonary anastomosis, and 7 patients had a Fontan. Two patients had cardiac transplantation after Fontan. Overall survival is 64% at 1 year, and 58% at 5 and 10 years. Most deaths occurred following Norwood operation (n = 5).

CHD necessitating single ventricle reconstruction associated with chromosome 22q copy number variants is not common, but typically occurs as a variant of hypoplastic left heart syndrome with the usual cytogenetic microdeletion. The most common neonatal surgical intervention performed is the Norwood, where most of the mortality burden occurs. Associated anomalies and medical issues may cause additional morbidity after cardiac surgery, but survival is similar to infants with other types of single ventricle disease.