Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study

Abstract

ObjectiveChromosome 22q11.2 deletion is the most commonly occurring known microdeletion syndrome. Deaths related to the syndrome have been reported, but the magnitude of death has not been quantified. This study evaluated the deletion's impact on survival and its clinical manifestations in a large cohort of Chilean patients.DesignDemographic and clinical data of individuals with 22q11 deletions diagnosed between 1998 and 2013 were collected from medical records and death certificates. Case fatality rate was calculated and compared with national vital statistics. OR with 95% CI analysis was used to assess the association between clinical manifestations and death.SettingGenetic services in tertiary care centres in Chile, following patients with 22q11.2 deletion.OutcomesFatality rate and associated factors.Results59 of 419 patients (14.1%) died during the study period at a median of 3.4 months (range 0 to 32 years of age). Factors associated with death included congenital heart disease (OR 5.27; 95% CI 2.06 to 13.99; p<0.0001), hypocalcaemia (OR 4.27; 95% CI 1.67 to 11.15; p<0.002) and airway malacia (OR 13.37; 95% CI 1.19 to 110.51; p<0.002). Patients with deletions and defects such as tetralogy of Fallot with or without pulmonary atraesia, truncus arteriosus or ventricular septal defect, had a 2.6-fold to 4.6-fold higher death rate compared with nationwide reports for the same types of defects.ConclusionsIn this cohort, we observed a death rate of 14.1%, implying that one in seven patients with 22q11 deletion died during the study period. Significant associations with cardiac defects, hypocalcaemia and airway malacia were observed. Furthermore, the death risk in patients with 22q11 deletion and cardiac defects exceeded the global figures observed in Chile for infants with structurally similar but apparently isolated anomalies. These observations indicate a need to identify patients who may require specific perioperative management to improve survival.

22q11.2 deletion syndrome

“…About 4% of all infants with 22q11.2DS succumb, with mortality figures exceeding those for infants with similar malformations 31,41 . Cardiac defects, hypocalcaemia and airway malacia (in which cartilage defects lead to collapsibility of the airway) are risk factors for early death, with median age at death of 3–4 months 31,41 . In adults, premature death occurs at median age in the 40s; causes are multiple, including sudden unexplained death 51 , but are not necessarily related to cardiac defects or psychotic illness 51 .…”

“…Today, most (90–95%) newly identified patients with 22q11.2DS are found to have de novo deletions — that is, neither parent has the 22q11.2 deletion 29 . However, owing to improved survival and thus higher reproductive fitness of individuals with 22q11.2DS, the prevalence, especially of the inherited types, is expected to increase 30,31 . As 22q11.2DS is a haploinsufficient disorder, approximately half of the children of individuals with 22q11.2DS will have the deletion.…”

“…In adults, premature death occurs at median age in the 40s; causes are multiple, including sudden unexplained death 51 , but are not necessarily related to cardiac defects or psychotic illness 51 . Larger studies are needed to more fully clarify mortality risks prospectively at all ages 31,41,51 .…”

22q11.2 Deletion Syndrome: Symptoms, Diagnosis, Treatment

“…Летальность на первом году жизни составляет около 4% и превышает показа-тели для детей с аналогичной мальформацией сердеч-но-сосудистой системы, но с отсутствием хромосомной микроделеции, усугубляясь аномалией крупных сосудов, гипокальциемией и трахеомаляцией [5,6].…”

“…В целом, врожденные пороки сердца являются основ-ной причиной летального исхода болезни у 87% детей с 22q11.2DS [5,30].…”