John Carey

Mortality in individuals with trisomy 18 has significantly decreased over the past 20 years, but there is scant literature addressing the prognosis and cause of death in individuals with trisomy 18 and survival past the first year of life (YOL). This study analyzed factors associated with mortality and cause of death in a retrospective cohort of 174 individuals with trisomy 18 and survival past the first YOL, the largest such series to date. Data were collected via retrospective survey of parents of affected individuals. Prenatal diagnosis of trisomy 18; postnatal respiratory distress; maternal age > 35 years; birthweight <2000 g; brain and spinal cord defect(s); atrial and/or ventricular septal defect(s); inability to feed orally without medical assistance; and failure to meet sitting and rolling milestones were associated with mortality in this sample. Cause of death was compared between our cohort of individuals with trisomy 18 and existing literature on those with mortality before the first YOL. Individuals with trisomy 18 with mortality after the first YOL demonstrated a predominance of infectious ( n = 10/22) and postoperative ( n = 6/22) contributing causes of death, in contrast to the existing literature, which shows a predominance of cardiopulmonary causes of death (e.g., cardiopulmonary arrest, pulmonary hypertension). These findings demonstrate that individuals with trisomy 18 and survival past the first YOL have unique medical needs, but further research is needed to develop clinical guidelines for this growing population.

Changes in medical intervention over the last decade have improved outcomes for individuals with trisomy 18, the second most common human aneuploidy syndrome at birth. As children with trisomy 18 live longer, a shared concern of medical experts and parents is the occurrence and treatment of seizures. Previously published surveillance guidelines for this condition have not addressed seizure management. Using parent‐reported data collected as part of the Tracking Rare Incidence Syndromes project, we report on the prevalence, course, and management of seizures in individuals with trisomy 18. Twenty‐eight percent (52/186) of individuals diagnosed with trisomy 18 in our retrospective cohort experienced generalized, focal, or mixed seizures at some point in their lifetime. For many individuals, seizures were effectively managed by broad‐spectrum anti‐seizure medications. Correlation analysis showed that focal and generalized seizures were more likely to occur in individuals who had previously experienced infantile spasms or central apnea. Electroencephalogram testing should be considered as part of a standard screening approach in individuals with trisomy 18 to enable early diagnosis and treatment of seizures. An international registry that incorporates parent‐reported and clinical data for patients with trisomy 18 may facilitate ongoing research and recruitment into clinical trials for seizure management.

It is here argued that the application of the term “minor anomalies” is often imprecise and likely outdated. In the past, the designation was used indiscriminately to refer to a great variety of unrelated morphogenetic phenomena. Also, the term does not discriminate between mild qualitative defects of development (mild malformations) and quantitative variants of normal structure. The human face was formed by natural and sexual selection. Morphological and morphogenetic analyses have shown that the human face with its skin, muscles, nerves, arteries, veins, glands, and lymphatics is a complex structure made up of progeny of ectoderm and mesoderm. Holoprosencephaly demonstrates graphically how these embryonic derivatives fit together sequentially. These derivatives are the adaptive units of the human organism, the result of stringent evolutionary forces uniting essential function to a minimum of structure. Before an “unusual” facial appearance is diagnosed as “abnormal”, phenotype analysis is required to determine if there is a family resemblance or if it is a pleiotropic structure. The facial structures of chimps and humans are homologous by virtue of descent from a common ancestor (Darwin, 1859). Differences in the appearance of these species reflect adaptive divergence over some 6–7 million years of evolution while retaining over 98–99% genetic identity. Both species may develop Down syndrome, evidence of similarly retained developmental plasticity. It has occurred to us that Dobzhansky's axiom (“Nothing in biology makes sense except in the light of evolution”) applies not only to genetics, but to all of medicine.