Phenotype of patients with late diagnosis of 22q11 deletion: a review and retrospective study.

Background: Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, typically presenting in neonates with congenital cardiac anomalies, hypocalcaemia and thymic hypoplasia. Some patients are diagnosed later in adolescence and adulthood, with less known about the clinical phenotype of these patients.

Aim: To summarise key clinical features in cases of 22q11DS diagnosed during adolescence and adulthood.

Methods: This is a retrospective cohort study of 22q11DS patients diagnosed after 13 years of age over 2010-2021, with a literature review of published cases highlighting other late diagnoses. The study was performed in a large multicentre tertiary health network in Melbourne, Australia. Patients diagnosed with 22q11DS after the age of 13 years were included in the study. Main outcome measures were key clinical features in cases of late diagnosis of 22q11DS.

Results: A literature search yielded 53 published case reports and one cohort study for review (62 subjects). Additionally, 10 cases of late diagnosis of 22q11DS were identified through a retrospective electronic medical chart review. Findings suggest that intellectual disability and learning difficulties, hypocalcaemia with hypoparathyroidism and facial dysmorphism remain key features in patients with a late diagnosis of 22q11DS, with hypocalcaemia being the most common presentation leading to diagnosis. Patients diagnosed in adulthood may lack classical clinical features of congenital cardiac anomalies and thymic hypoplasia. Immunological consequences of 22q11DS are also an important late-onset consideration. Atypical features may include basal ganglia calcification.

Conclusions: Chromosome 22q11DS has diverse clinical features and a highly variable phenotype, likely contributing to underdiagnosis and later diagnoses.