The numbers behind this rarity are striking. Trisomy 22 is found in 2 to 5 percent of spontaneous abortions across all populations studied, making it the second most common autosomal trisomy in pregnancy loss, behind only trisomy 16. The vast majority of affected fetuses are lost in the first trimester. The estimated incidence of liveborn complete trisomy 22 is between 1 in 30,000 and 1 in 50,000 births. As with most aneuploidies, increased maternal age is a risk factor, and the extra chromosome most often arises from a non-disjunction error during maternal meiosis one, when the chromosome pair fails to separate properly. More affected infants are female, a pattern the authors attribute to higher pregnancy loss among male fetuses, a sex ratio seen in other aneuploidies as well.

Because complete trisomy 22 is a lethal condition, the phenotypic spectrum has been largely characterized through reports of mosaic trisomy 22, in which only a fraction of cells carry the extra chromosome. Mosaic patients can survive into adolescence and adulthood, with documented cases alive at 7, 14, 17, and even 19 years of age, though they typically show growth restriction, developmental delay, and variable congenital anomalies. In complete trisomy 22, the most common cause of death is respiratory insufficiency. Reported features include intrauterine growth restriction, microcephaly, congenital heart disease, renal anomalies, anal atresia, thumb anomalies, hypotonia, and dysmorphic facies with hypertelorism, epicanthal folds, a flat nasal bridge, and low-set ears. Neonates with complete trisomy 22 more often show anomalous great vessels, whereas septal defects are more commonly reported in mosaic aneuploidy.

The baby in this report was born at 37 weeks and 1 day via spontaneous vaginal delivery to a 28-year-old mother with one prior spontaneous miscarriage. The father was also 28, the parents were non-consanguineous, and there were no reported teratogenic exposures. Prenatal ultrasounds had already flagged a large ventricular septal defect, an abnormal aorta, dilated small bowel, a pelvic right kidney, and micrognathia. A non-invasive prenatal testing result was inconclusive but suggested a possible sex chromosome anomaly involving the X chromosome, with low risk for trisomy 13, 18, and 21, triploidy, and 22q11.2 microdeletion syndrome. Chromosome 22 was not tested. No invasive prenatal genetic tests were obtained per the family’s preference, and the final diagnosis became available only after the patient’s death.

At delivery, the infant was small for gestational age, under the 10th percentile for weight at 1,750 grams, length at 42.5 centimeters, and head circumference at 30 centimeters. Her Apgar scores were 2, 4, and 4 at 1, 5, and 10 minutes. She was cyanotic with a weak cry and unresponsive to stimulation. Bagging ventilation failed to improve her heart rate or oxygen saturation, and intubation was unsuccessfully attempted five times. Chest compressions were initiated and epinephrine was given before a laryngeal mask airway was successfully placed. She was later intubated using a 2.9 millimeter rigid bronchoscope with a 3.0 millimeter endotracheal tube, after clinicians noted that her epiglottis and airway were extremely anterior and difficult to visualize. Rigid tracheoscopy revealed a patent trachea and mainstem bronchi without apparent tracheoesophageal fistula.

Physical examination and imaging revealed a constellation of congenital anomalies. She had a single umbilical artery, microcephaly, dysmorphic facial features with hypertelorism, downward-slanting palpebral fissures, microphthalmia, bilateral microtia with periauricular tags, and neck webbing. Ocular findings included an absent red reflex, corneal haze with an irregular pupil on the right, and microcornea on the left. She had an imperforated anus with rectovestibular fistula, bilateral clinodactyly of the fifth digits, and bilateral distal and proximal transverse palmar creases running in parallel across the full width of the palm. An echocardiogram within 24 hours of birth showed Tetralogy of Fallot, a large secundum atrial septal defect, a large patent ductus arteriosus, a dilated main pulmonary artery, thickened pulmonary, aortic, and tricuspid valves, and mild hypoplasia of the transverse aortic arch. Abdominal ultrasound revealed low-lying, small-for-age kidneys. Head ultrasound showed absence of the septum pellucidum, and a three-hour video electroencephalogram on day four showed diffuse cerebral dysfunction with no distinction between awake and sleep states, though no seizures.

The clinical course deteriorated rapidly. She developed severe hypoglycemia and bilateral pneumothorax on day 1 of life, requiring bilateral chest tubes. Ventilation remained challenging despite high settings, and surfactant and inhaled nitric oxide produced no improvement. She received a five-day course of ampicillin and ceftazidime for maternal chorioamnionitis, and on day four was diagnosed with coagulase-negative Staphylococcus sepsis, for which vancomycin was started. Persistent thrombocytopenia required multiple platelet transfusions, and impaired thermoregulation required warmer therapy. By day four, evidence of pulmonary hypertension emerged with predominantly right-to-left shunting across the patent ductus arteriosus, and she required daily hydrocortisone for hypotension. On day six, her hypotension worsened, requiring epinephrine and calcium chloride. On day seven, life-sustaining therapies were withdrawn, and she passed away approximately 1.5 hours later. A mitogen-stimulated peripheral blood chromosome study showed trisomy 22 in all 50 cells analyzed, with the karyotype 47,XX,+22. Autopsy was not performed.

The authors note that the diagnosis was established only after the patient had passed, causing significant uncertainty for both the multidisciplinary care team and the family, who were required to make complex medical decisions without adequate time to fully understand the underlying condition and its prognosis. The case also highlights the limits of current prenatal screening. Both the American College of Medical Genetics and Genomics and the American College of Obstetricians and Gynecologists recommend that non-invasive prenatal testing be made available to all pregnant patients regardless of risk, but most laboratories only report abnormalities in chromosomes 13, 18, 21, and the sex chromosomes, and do not screen for rarer aneuploidies like trisomy 22. The testing relies on placental rather than fetal DNA, which can limit its ability to fully detect fetal genetic conditions and necessitates confirmatory invasive tests such as chorionic villus sampling or amniocentesis. The authors suspect the positive sex chromosome screen in this case was a false-positive result unrelated to the confirmed trisomy 22, though a chromosomal microarray was not completed, so a small copy number variant could not be ruled out.

The diagnostic landscape is evolving. Chromosomal microarray analysis is recommended as a first-tier diagnostic test for fetuses with structural anomalies, because it identifies all aneuploidies detected by karyotype while additionally detecting submicroscopic copy number variants in approximately 6 percent of cases with a normal karyotype. Whole exome sequencing and whole genome sequencing can provide superior diagnostic yields compared to microarray alone, and while current guidelines recommend them only when other tests have failed to arrive at a diagnosis in a fetus with multiple congenital anomalies, these technologies can provide earlier and more precise characterization of complex fetal phenotypes.

The case contributes to the limited literature on complete trisomy 22 and highlighted additional findings not previously reported to the authors’ knowledge, including corneal haze, microcornea, and absence of the septum pellucidum. The most common eye abnormality reported in mosaic and complete trisomy 22 is coloboma. By better understanding the clinical presentation, the team hopes to facilitate early recognition, appropriate management, and counseling. Given the high likelihood of fetal demise or limited life expectancy, the authors emphasize that preparing the family for potential outcomes and collaboratively planning interventions that align with the family’s values and goals becomes essential from the point of initial diagnosis, underscoring the importance of interdisciplinary collaboration and adaptability in providing optimal care for this rare and devastating condition.

Subject of Research: A clinical case report of a liveborn female neonate with complete trisomy 22, documenting congenital anomalies, neonatal management, and prenatal diagnostic challenges.

Article Title: Liveborn trisomy 22: a case report

Article References: Jares Baglivo, S., Morand, M. P., Velagaleti, G. V. N., Jain, S. K., & Cooney, E. (2026). Liveborn trisomy 22: a case report. Frontiers in Pediatrics, 14, Article 1920011. https://doi.org/10.3389/fped.2026.1920011

Image Credits: AI Generated

DOI: 10.3389/fped.2026.1920011

Keywords: trisomy 22, aneuploidy, case report, neonatology, prenatal testing, genetics, Liveborn, trisomy, case, report, scientific research