Rhizomelic chondrodysplasia punctate morbidity and mortality, an update

Duker AL, Niiler T, Kinderman D, Schouten M, Poll-The BT, Braverman N, and Bober MB. (2019) Rhizomelic chondrodysplasia punctata morbidity and mortality, an update. American Journal of Medical Genetics Part A. 1–5. https://doi.org/10.1002/ajmg.a.61413

Rhizomelic chondrodysplasia punctata morbidity (RCDP) is a class of genetic disorders caused by an inability to synthesize plasmalogens (a class of phospholipids containing a vinyl-ether bond) resulting in severe physical disabilities and cognitive impairment. RCDP is incredibly rare, with a prevalence of 1:100,000 live births and less than 100 known cases in North America. Until recently, there were only two references available that evaluated survival in RCDP. The first was from 1990, stating that most children with this diagnosis die within their first year (1), and the second from 2003 indicating that 50-60% survive to five years of age (2). A new study from Nemours/Alfred I. duPont Hospital for Children showed that the five-year survival probability was 75%. They went on to further evaluate the association between survival probability in RCDP and various clinical variables. Their results determined that survival is most closely associated with the extent of plasmalogen deficiency.

To determine the survival probability within this cohort and the role of sex, location, type of RCDP, and level of plasmalogen deficiency in survival, they employed Kaplan-Meier survival curves on a total of 66 individuals from the US and Dutch (Amsterdam University Medical Center) registries. There were no differences between the Dutch and US groups, showing that geographical location does not have an effect on the mortality rate of this disease; as well, no difference was seen between sex and type of RCDP (Type 1 compared to Type 2, as no volunteers were diagnosed with Types 3, 4, or 5 in either cohort).

The key findings from Duker et al was that the only significant variable influencing the survival probability of RCDP is the level of the plasmalogen deficiency, which can vary. The cohort was split into two groups, those with “classic” RCDP where they had less than 0.05 for C18:0 DMA/C18:0 fatty acid and 0.02 for C16:0 DMA/C16:0 fatty acid and “non-classic” if they were above those values. Those with “classic” RCDP were found to have a lower survival probability than those with “non-classic”. Although for many years this disorder was commonly thought to cause death within the first year of life, the results from this study provide hope and reassurance that this is not the case and also explained that the prior survival expectancy may have been based on a very specific subset within all of RCDP prognoses. This article clearly shows the importance that the level of plasmalogen deficiency has on the severity of RCDP and that there is a spectrum of RCDP phenotypes as a result.

1) Wardinsky TD, Pagon RA, Powell BR, McGillivray B, Stephan M, Zonana J, and Moser A. (1990) Rhizomelic chondrodysplasia punctata and survival beyond one year: A review of the literature and five case reports. Clinical Genetics, 38, 84–93.

2) White AL, Modaff P, Holland-Morris F, and Pauli RM. (2003). Natural history of rhizomelic chondrodysplasia punctata. American Journal of Medical Genetics. Part A, 118A(4), 332–342.