Mortality in Patients with 22q11.2 Rearrangements
Abstract
:1. Introduction
2. Patients, Materials, and Methods
2.1. Clinical Criteria
2.2. Chromosomal and Molecular Studies
2.3. Study Limitations
3. Results
3.1. Causes of Death and Clinical Findings
3.2. Genomic Findings
4. Discussion
4.1. Mortality of 22 q11.2 Deletions Is Higher than in Other Rearrangements
4.2. Congenital Heart Diseases Are the Determining Factor of Mortality
4.3. Decrease in Mortality in the Past Decades Depends on the Improvement in Surgical Techniques for Heart Disease
4.4. Comparison with Other Series
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cause | Age at Death: Range in Years (Median) | Number of Patients | Percentage (%) |
---|---|---|---|
Cardiac | 1 month, 15 days (range 3 days–27 years) | 12 | 57.14 |
Sepsis | 1 year, 7 months (range 15 months–2 years, 11 months) | 2 | 9.52 |
Unknown | - | 2 | 9.52 |
Cardiac + respiratory failure | 15 days | 1 | 4.76 |
Cardiac + hematological | 15 years | 1 | 4.76 |
Respiratory failure | 1 year | 1 | 4.76 |
Renal failure | 33 days | 1 | 4.76 |
Cardiac + sepsis | 34 years | 1 | 4.76 |
Total | 3 months, 18 days (range 3 days–34 years) | 21 | 100 |
Patient Information | Details of Death | Clinical Findings | Molecular Genetic | Comments | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Case | Gendre | Ethnicity | Age at Diagnosis | Age of Death | Cause of Death | Cardiac | Neuropsychiatric | Others | Rearrangement | Inheritance | Test Platform | |
1 | F | White Mediterranean (non-Finish) | 7 years, 3 months, 7 days | 27 years | Cardiorespiratory arrest secondary to cardiac surgery | TA type II (surgically intervened 3 months), VSD, pulmonary stenosis, severe cyanotic CHD, RAA. Surgically intervined. | Hyperactive behavior, epilepsy, ADHD, GDD | Hypoparathyroidism, microcephaly, dysmorphic facies, myopia (8 dioptres) | Deletion A-B | Inherited mother | FISH | |
2 | F | White Mediterranean (non-Finish) | 7 days | Unknown | Unknown | TF, pulmonary valve agenesis. | Deletion | De novo | FISH | |||
3 | M | White Mediterranean (non-Finish) | 1 day | 5 days | Ischemic heart disease | TA type 1, anomalous left subclavian artery, VSD. | SGA, dysmorphic facies, slightly elongated fingers | Deletion A-D 2.56 Mb | De novo | CMA | Ultrasound week 31 with suspicion of structural congenital heart disease. Has a phenotypically normal identical twin brother | |
4 | M | Amerindian (South-American) | 4 days | 15 years | CHD and bleeding due to thrombocytopenia | LV hypoplasia, DORV, single atrium, mild tricuspid insufficiency, CoA, atrioventricular conduction disorders. Surgically intervined. | GDD | Severe hearing loss, brachycephaly, dysmorphic features, aphonia, visual deficit, ischemic colitis, biliary sludge, portal hypertension secondary to Fontan surgery. | Duplication 22q11.23-q12.1 (1.55 Mb) | De novo | CMA + MLPA | Ultrasound week 25 with suspicion of structural congenital heart disease. Deletion 53.7 Kb in chromosome 6. Deletion 22q12.3q13.1 (3.5 Mb). Duplication 22q13.31 (2.53 Mb) |
5 | M | White Mediterranean (non-Finish) | 1 day | 15 days | Hypoxemia and progressive hemodynamic failure after cardiovascular surgery | TA type II, isolated aortic arch, PAH, RAA. Surgically intervined. | Dysmorphic facies, palate with abnormal dermatoglyphsv Velopharyngeal incompetence, microcephaly, bilateral skin ectasia, small umbilical hernia | Deletion A-D | De novo | FISH | Carrier of an inversion on chromosome 9 [46, XY, inv (9) (p11q13)] inherited from his father. Benign variant. | |
6 | M | White Mediterranean (non-Finish) | 2 years | 2 years, 11 months | Sepsis | VSD, pulmonary valve atresia, RAA, $patent DA. | Deletion A-D | Unknown | FISH | |||
7 | M | White Mediterranean (non-Finish) | 1 day | 9 days | Cardiorespiratory arrest secondary to cardiac surgery | IAA type A, DA, AVVR, single atrium, LSVC draining the coronary sinus, CAVC. Surgically intervined. | Multifactorial anaemia. | Deletion A-D | Unknown | FISH | Ultrasound week 30 with diagnosis of CHD+single umbilical artery | |
8 | F | White Mediterranean (non-Finish) | 6 days | 10 days | Complications derived from CHD | TA, VSD, PAH. | Hypocalcemia | Deletion A-D | Inherited mother | FISH | ||
9 | F | White Mediterranean (non-Finish) | 26 days | 33 days | Post-surgical renal failure | VSD, TA type I, extrasystoles, PAH. Surgically intervined. | Dysmorphic facies | Deletion A-D | De novo | FISH | ||
10 | M | Ameridian (South American) | 1 day | 1 year | Respiratory failure ventilatory restrictive with hypercapnia | Pulmonary atresia, VSD, RAA, pulmonary hypoaflow, pacemaker, arterial hypertension, MAPCA. Surgically intervined. | Chronic respiratory disease, CMPA, GERD, dysphagia | Deletion A-D (2.61 Mb) | De novo | CMA | Ultrasound week 30 with diagnosis of CHD | |
11 | F | White Mediterranean (non-Finish) | 1 month, 8 days | 21 years | Sudden Death | IAA, VSD, ASD. Surgically intervened. | ASD, GDD, seizures, attention deficit | Premature, short stature, arched palate, thyroid nodules, dysmorphic facies, altered phosphocalcium metabolism | Deletion A-D | De novo | FISH | |
12 | F | White Mediterranean (non-Finish) | 1 day | 2 months, 13 days | Cardiorespiratory arrest secondary to cardiac surgery | TF, pulmonary valve agenesis with severe pulmonary stenosis, RAA, severe RV dilation, VSD. Surgically intervined. | Symptomatic hypocalcemia, hypothyroidism, SGD, multifactorial anemia, polymalformative syndrome, ischemia in left leg, dysmorphic features | Deletion A-D | De novo | FISH | ||
13 | M | White Mediterranean (non-Finish) | 16 days | 26 days | Complications derived from CHD | IAA type B, large VSD, bicuspid aortic valve, subaortic stenosis, large patent DA, ascending aorta hypoplasia, ASD. Surgically intervined. | Dysmorphic facies, hepatopathy with jaundice and coagulation disorders, hypocalcemia, lymphopenia | Deletion A-D | De novo | FISH | ||
14 | M | White Mediterranean (non-Finish) | 10 days | 2 months, 2 days | Cardiorespiratory arrest | VSD, ASD, small DA, anomalous pulmonary venous drainage. Surgically intervined. | Premature, dysmorphic facies, aplasia of both thumbs and radius, lumbar hemivertebra, anal atresia, cholestasis, cleft palate | Marker chromosome 22 (partial trisomy) | De novo | FISH | Cat Eye Syndrome | |
15 | M | White Mediterranean (non-Finish) | 5 days | 17 months | Sepsis | VSD, IAA, auriculoventricular block with external pacemaker. Surgically intervined. | Lymphopenia with low CD4, coloboma, bronchopulmonary dysplasia, GERD, hiatus hernia, multiple thromboses, velopharyngeal incompetence | Deletion A-D | De novo | FISH | ||
16 | F | White Mediterranean (non-Finish) | 10 days | 8 months | Unknown | TA type I. | Deletion A-D | De novo | FISH | |||
17 | F | Ameridian (South American) | 1 month, 20 days | 4 months, 25 days | Complications derived from CHD | VSD, pulmonary valve atresia. | Dysmorphia | Deletion A-D (3 Mb) | De novo | MLPA | ||
18 | M | White Mediterranean (non-Finish) | 1 day | 3 days | Cardiorespiratory arrest secondary to cardiac surgery | Severe aortic stenosis, IAA type B, VSD, bicuspid aortic, valve, DA, patent foramen ovale. Surgically intervined. | Dysmorphic features | Deletion A-D | De novo | FISH | ||
19 | M | White Mediterranean (non-Finish) | 20 years, 21 days | 34 years | Cardiorrespiratory arrest + sepsis | Pulmonary valve atresia, PAH, VSD, MAPCA. Not surgically intervined. | Learning disabilities, GDD | Dysmorphic features, partial agenesis right hemithyroid, articulation disorder, right severe hypoacusis, polyglobulia, antiphospholipid syndrome, hyperuricemia and gout, mild hypocalcemia, ictus, clubfoot | Deletion A-D (3 Mb) | De novo | MLPA | |
20 | M | White Mediterranean (non-Finish) | 1 day | 12 days | Cardiorespiratory arrest secondary to cardiac surgery | TA type I, IAA, mild tricuspid insufficiency, PAH, VSD, ASD ostium secundum, paroxysmal supraventricular tachycardia. Surgically intervined. | Hypoplasia of the depressor labii inferioris muscle, right cryptorchidism | Deletion A-D | De novo | FISH | Translocation t (14;16)(q32.3;p13.1) inherited from the mother | |
21 | M | White Mediterranean (non-Finish) | 3 days | 7 months | Complications derived from CHD | TF, incompetent persistent foramen ovale, mild PAH. | Dysmorphic features, polymalformation, supernumerary spleen, corpus callosum agenesis | Deletion A-D (3 Mb) | De novo | FISH |
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Cilio Arroyuelo, M.; Tenorio-Castano, J.; García-Moya, L.F.; Parra, A.; Cazalla, M.; Gallego, N.; Miranda, L.; Mori, M.Á.; García-Gueretta, L.; Labrandero, C.; et al. Mortality in Patients with 22q11.2 Rearrangements. Genes 2024, 15, 1146. https://doi.org/10.3390/genes15091146
Cilio Arroyuelo M, Tenorio-Castano J, García-Moya LF, Parra A, Cazalla M, Gallego N, Miranda L, Mori MÁ, García-Gueretta L, Labrandero C, et al. Mortality in Patients with 22q11.2 Rearrangements. Genes. 2024; 15(9):1146. https://doi.org/10.3390/genes15091146
Chicago/Turabian StyleCilio Arroyuelo, Melisa, Jair Tenorio-Castano, Luis Fernández García-Moya, Alejandro Parra, Mario Cazalla, Natalia Gallego, Lucía Miranda, María Ángeles Mori, Luis García-Gueretta, Carlos Labrandero, and et al. 2024. "Mortality in Patients with 22q11.2 Rearrangements" Genes 15, no. 9: 1146. https://doi.org/10.3390/genes15091146