Characterization of Autoimmune Thyroid Disease in a Cohort of 73 Paediatric Patients Affected by 22q11.2 Deletion Syndrome: Longitudinal Single-Centre Study

Abstract

Background. Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) is the most frequent microdeletion syndrome and is mainly characterized by congenital cardiac defects, dysmorphic features, hypocalcemia, palatal dysfunction, developmental delay, and impaired immune function due to thymic hypoplasia or aplasia. Thyroid anomalies are frequently reported in patients with 22q11.2DS, although only a few well-structured longitudinal studies about autoimmune thyroid disease (ATD) have been reported. Aim. To longitudinally evaluate the frequency of thyroid anomalies and ATD in patients with 22q11.2DS. Patients and Methods. Pediatric patients with a confirmed genetic diagnosis of 22q11.2DS were recruited and followed up on longitudinally. Clinical, biochemical, and immunological data were collected, as well as thyroid function, autoimmunity, and thyroid sonographic data. Results. The study included 73 children with 22q11.2DS, with a mean follow-up duration of 9.51 ± 5.72 years. In all, 16 of the 73 enrolled patients (21,9%) developed ATD before 18 years of age (mean age 12.92 ± 3.66 years). A total of 20.5% developed Hashimoto’s Thyroiditis (HT), of whom 50% required L-thyroxine treatment; 1.4% developed Graves Disease. Thyroid hypoplasia was found in 6/16 patients with ATD and left lobe hypoplasia in 9/16 patients. These features were also found in patients affected by 22q11.2DS without ATD. Among patients who developed ATD, at the first altered ultrasound scan, the most frequent anomalies suggestive of thyroiditis were inhomogeneous echotexture, diffuse or irregular hypo-echogenicity, and vascular overflow. Conclusion. We strongly recommend periodic screening of thyroid function and for autoimmunity in patients affected by 22q11.2DS. Along with blood tests, ultrasound scans of the thyroid gland should be performed periodically since some patients who go on to develop an ATD could have specific anomalies on ultrasound prior to any other anomaly.

Case report: Effectiveness of sirolimus in treating partial DiGeorge Syndrome with Autoimmune Lymphoproliferative Syndrome (ALPS)-like features

“…The immune dysregulation manifestations described in DGS include impaired antibody immune response resulting in poor response to vaccines and IgA deficiency ( 12 – 14 ). Autoimmune diseases such as juvenile rheumatoid arthritis, ITP, autoimmune hemolytic anemia, and Hashimoto thyroiditis are collectively common in DGS patients ( 14 – 17 ). The patient in the present study was shown to have an ALPS-like phenotype in many aspects, including decreased Tregs, increased IL-10 levels, and elevated DNT cells ( 6 ).…”

Understanding the Variability of 22q11.2 Deletion Syndrome: The Role of Epigenetic Factors

“…However, previous studies suggest that the susceptibility to recurrent infections is primarily related to the anatomical alterations associated with the syndrome [ 53 ] {Giardino, 2019 #1}. Patients with 22q11.2DS may also develop immune dysregulatory manifestations [ 54 ] including allergy and asthma, autoimmune diseases such as juvenile idiopathic arthritis [ 55 ], hemolytic anemia [ 56 ], idiopathic thrombocytopenia [ 57 ], autoimmune thyroid dysfunction [ 58 , 59 ] and others.…”

Chromosome 22q11.2 Deletion Syndrome: A Comprehensive Review of Molecular Genetics in the Context of Multidisciplinary Clinical Approach

“…Thyroid autoantibodies, particularly anti-thyroperoxidase antibodies, have been found in up to 5% of children and in approximately 30% of adults affected with 22q11.2 DS [73]. Two clinical disease entities of autoimmune thyroiditis have been reported in children with the syndrome: Hashimoto thyroiditis occurs in 20% of them and is characterized by inhomogeneous thyroid echostructure and progression from normal function to hypothyroidism and, less frequently, Grave's disease, which presents with overt hyperthyroidism and is observable in 1.4% of affected pediatric patients [67,[73][74][75][76][77]. Congenital thyroid gland abnormalities have also been recognized in children with 22q11.2 DS and include an absent thyroid isthmus, retrocarotid and retroesophageal extension, and absence/hypoplasia of the left thyroid lobe.…”