Late diagnosed DiGeorge syndrome in a 44-year-old female: a rare cause for recurrent syncopes in adulthood—a case report

Abstract

Background DiGeorge syndrome, also known as ‘CATCH 22’, is the most common deletion in humans and is one of the velocardiofacial syndromes. It is characterized by a specific facial phenotype, and structural and functional abnormalities in the cardiac and endocrine systems. One form of endocrine system dysfunction is hypocalcaemia, which causes arrhythmic events and can result in a transient loss of consciousness. We present a case highlighting the late diagnosis of DiGeorge syndrome in a patient with recurrent episodes of syncope due to suspected arrhythmic events secondary to hypocalcaemia. Case summary A 44-year-old woman was referred for further investigation of recurrent syncope episodes and documented transient QT-prolongation with hypocalcaemia. Previous detailed cardiological examination, including invasive procedures such as coronary angiography and cardiac magnetic resonance tomography, was unremarkable. Slight characteristic facial dysmorphia and transient hypocalcaemia were strongly suggestive of DiGeorge syndrome. The diagnosis was confirmed by genetic testing. Calcium substitution was initiated and no recurrent episodes of syncope or arrhythmic events were reported during 12 months of follow-up. Discussion Clinical presentation and time of manifestation of the DiGeorge syndrome varies widely depending on the mutation expression extent. An atypical disease course may delay the diagnosis and appropriate management of affected patients. In this case, confirmation of the diagnosis allowed the initiation of appropriate treatment, reducing the risk for further events. Given that syncope and arrhythmia can be the first and only manifestation of late-onset DiGeorge syndrome, specialists in adult cardiology need to be aware of this presentation.

Síndrome de DiGeorge (deleção do cromossomo 22q11.2): manejo e prognóstico

“…A síndrome, no entanto, pode passar despercebida por muitos anos ou até por toda a vida, tendo em vista que existem pacientes com pouco ou nenhum sintoma. Por outro lado, quando existe a suspeita pela equipe médica, a doença pode ser diagnosticada por meio do exame de sangue (ISGANDAROVA et al, 2021;RIZVI et al, 2018).…”

“…As técnicas empregadas são a Hibridização Genômica Comparativa baseada em microarray (aCGH), a qual permite investigar simultaneamente milhares de sequências genômicas para a detecção de falhas segmentares invisíveis no exame de cariótipo, e a Hibridização por Fluorescência in situ (FISH), a qual é capaz de detectar a deleção hemizigótica de três megabases (Mb) no braço longo do cromossomo 22, com inclusão do gene TBX1 entre repetições de baixa cópia LCR22-1 e LCR22-3 (ISGANDAROVA et al, 2021;RIZVI et al, 2018).…”

“…Ao eletroencefalograma, o neurologista notou aumento de atividade epiléptica, sendo prescrito levetiracetam 500 mg duas vezes ao dia, e foi assumido que a causa foi, também, a hipocalcemia. Na admissão do hospital, foi realizado um ECG que evidenciou taquicardia supraventricular autolimitada súbita, sem compromisso hemodinâmico (ISGANDAROVA et al, 2021).…”

“…Por meio do raciocínio clínico, tais características faciais combinadas à hipocalcemia transitória foram sugestivas da síndrome de DiGeorge. Através do teste genético, o diagnóstico foi confirmado, com evidência da microdeleção em 22q11.2 (Figura 2) (ISGANDAROVA et al, 2021). A substituição de cálcio foi iniciada e nenhum episódio recorrente de síncope ou eventos arrítmicos foram relatados durante 12 meses de acompanhamento.…”

Fever of Unknown Origin Reveals a Missed Diagnosis of DiGeorge Syndrome in a 21-Year-Old Female

“…DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a rare multisystem disorder but the most frequent microdeletion disorder with an incidence of approximately 1:4,000 [ 1 , 2 ]. This syndrome is typically diagnosed in young children less than two years old; however, a late diagnosis of DiGeorge syndrome (after 10 years of age) has been made, although the true incidence is unknown [ 3 ]. Newborn screening has been performed in the United States since 2008 through severe combined immunodeficiency (SCID) screening tests using quantitative PCR (qPCR) to recognize low levels of T-cell receptor excision circles (TRECs).…”