EP467: Prenatal genetic testing can lead to (almost) self-fulfilling prophecy: Diastrophic dysplasia as an example

Abstract

From a diagnostic perspective, variants in SLC26A2 gene cause the spectrum of skeletal dysplasias including in-utero lethal achondrogenesis type 1B (OMIM: 600972), atelosteogenesis type 2 (OMIM: 256050), diastrophic dysplasia (OMIM: 222600) and multiple epiphyseal dysplasia (OMIM: 226900). Historically, individuals diagnosed with atelosteogenesis type 2 have had poor health outcomes and die in the perinatal period, whereas those with diastrophic dysplasia have had longer, potentially even typical lifespans. However, objective criteria to distinguish these two conditions prenatally does not exist. As is the case with many skeletal dysplasias, and recessive conditions in general, genetic testing alone cannot predict where along the spectrum of conditions an infant will present. With advancements in medical technology, we begin to question the potential of infants diagnosed with “lethal” skeletal dysplasias based on findings of a genetic test report. We present two children from two different families who endured unnecessary trauma in their quest to seek care for their child. In both cases, a prenatal ultrasound in the second trimester noted concerns for skeletal dysplasia, prompting an amniocentesis. Testing identified compound heterozygous variants in the SLC26A2 gene. Based on the interpretation of the genetic testing report and ultrasound findings, both families, in different institutions, were provided a diagnosis of atelosteogenesis type 2. This was counseled as a lethal skeletal dysplasia, and options presented were termination or comfort care if the choice was made to continue to term. Both families opted to continue the pregnancy and following delivery were discharged on hospice to homes that were not equipped for a new infant. Both infants had cleft palates, and neither family was trained on how to properly feed their baby. In both cases, once the infant outlived expectations and the family chose to pursue life-sustaining therapies, they faced significant challenges obtaining the necessary medical care for their child. At a few months of age, both infants, who had survived to this point despite any medical interventions, were admitted to the hospital due to malnutrition and weight loss upon their first visit with a specialist. Parents are faced with life-altering decisions when the diagnosis of a “lethal” skeletal dysplasia is given in a prenatal setting. When families decide to continue a pregnancy with a suspected poor prognosis, it is imperative that counseling include recognition of the nuance of a spectrum of disorders and the possibility for survival with life-sustaining interventions. If comfort care is agreed upon, a plan should be made on how a family could seek medical care if the child outlives expectations and/or the family wants to reassess their child’s care plan after delivery.