An increased prevalence of thyroid disease in children with 22q11.2 deletion syndrome

Abstract

We reviewed the health records of pediatric patients with 22q11.2 deletion syndrome (22q11.2 DS) seen over a 5-year period in our 22q11.2 DS multidisciplinary clinic. We determined the prevalence of thyroid dysfunction in this population, in comparison to general population data. Statistical tests were applied to investigate trends in gender differences, thyroid disease subtype and co-morbid conditions in the patients identified with thyroid disease. Of 169 subjects (92 male, 77 female) 9.5% had overt thyroid disease; of these, 1.8% had hyperthyroidism and 7.7% had hypothyroidism; 42% of patients with subclinical or prodromal thyroid disease progressed to overt disease. Our data indicate that thyroid disease prevalence in the 22q11DS pediatric population is significantly higher than that in the general pediatric population Furthermore, over 1/3 of patients in our study population who presented with subclinical thyroid disease progressed to overt disease, requiring medical therapy. Thyroid disease screening should be incorporated into routine medical management of children with 22q11.2 DS. Guidelines for screening individuals with 22q11.2 DS are presented.

Autoimmune Thyroid Disease in Specific Genetic Syndromes in Childhood and Adolescence

“…Interestingly, among patients with thyroidopathy the female to male ratio was 2.2, which is lower than the one reported in the general pediatric population. Furthermore, of those with prodromal or subclinical thyroid disease, 42% progressed to overt thyroid disease within a mean follow-up time of 27.6 months, necessitating medical treatment (135). In a previous study conducted in adults with 22q11.2DS the frequency of hypothyroidism reached 20.5% (136).…”

“…In case of subclinical thyroid disease, thyroid function tests (TFTs) should be repeated in a 4-6 months' time interval. If subclinical disease persists (and in case of overt thyroid disease), a thyroid ultrasound should be performed in order to exclude structural anomalies of the gland (135). Medical treatment for subclinical disease should be offered if TSH levels remain abnormal despite normal FT4 levels in the presence of suggestive signs/symptoms and/or positive TPO antibodies and/or goiter or thyroid hypoplasia.…”

Congenital heart diseases and cardiovascular abnormalities in 22q11.2 deletion syndrome: From well‐established knowledge to new frontiers

“…Indeed, besides CHDs, patients with 22q11.2DS may have many other conditions that increase their risk for cardiovascular diseases (CVDs). Some of these are secondary to other systemic conditions associated with 22q11.2DS, such as hypocalcemia, or to thyroid disorders that may cause arrhythmias, autoimmune disorders, chronic kidney disease that may cause hypertension and electrolytes imbalance (Cheung et al, 2014; Choi et al, 2005; Devriendt, Swillen, Fryns, Proesmans, & Gewillig, 1996; McDonald-McGinn et al, 2015; McLean-Tooke, Spickett, & Gennery, 2007; Shugar et al, 2015). Some of these conditions predisposing to CVDs have a multifactorial basis including genetic predisposition and psychiatric and behavioral problems associated with the 22q11.2 deletion, low physical activity due to fatigue/hypotonia/ developmental delay, as well as side effects of some pharmacological therapies (e.g., antipsychotic and antiepileptic treatment) resulting in obesity, impaired lipid metabolism, and diabetes mellitus (Choi et al, 2005; Fung et al, 2015; Kennedy et al, 2014; Lin et al, 2008; Mercer-Rosa et al, 2015; Philip & Bassett, 2011; Voll et al, 2017).…”

Neurodevelopmental outcome in 22q11.2 deletion syndrome and management

“…Known person-specific risk factors with implications for brain development and neurodevelopmental outcome in 22q11.2 DS include having the 22q11.2 deletion syndrome (by definition), origin of the deletion (inherited deletions may result in a more-severe cognitive phenotype, related to a combination of socio-economic factors and heritable components contributed by the unaffected parent) (De Smedt, 2007; Swillen et al, 1997), genetic variation within the 22q11.2 region (Gothelf et al, 2005; Raux et al, 2007), variants in genes on the intact 22q11.2 (McDonald-McGinn et al, 2013), prematurity, untreated neonatal hypocalcemia (Cheung, George, & Andrade, 2014), perioperative seizures (McDonald-McGinn et al, 2015) and undetected and untreated thyroid disease in children with 22q11 DS (Shugar et al, 2015). However, much work is still to be done in identifying other possible risk factors contributing to the neurodevelopmental outcome in 22q11.2 DS such as size of the deletion, genes within the region ( COMT, PRODH, TBX1, CRKL1 , etc.…”