All Patients With a Cerebral Palsy Diagnosis Merit Genomic Sequencing

Abstract

Cerebral palsy is a clinically diagnosed neurodevelopmental disorder with a broad phenotype. Until recently, cerebral palsy was often incorrectly assumed to be generally associated with birth asphyxia, birth trauma, or extreme prematurity. Most individuals with cerebral palsy have appropriately received neuroimaging.

Implications of Genetic Variants in Cerebral Palsy—Reply

“…CP describes a group of permanent disorders that are attributed to nonprogressive lesions in the developing fetal or infant brain. 4 However, the related phenotypes of some so-called CP genes are neurodegenerative and characterized by a progressive pattern, which is inconsistent with the basic nonprogressive element in the CP definition. For example, mutations in SPAST, considered the number 2 causative gene, cause progressive bilateral lower limb spasticity.…”

“…It is true that rigorous functional validation studies of a candidate CP gene are challenging and have only been conducted for a handful of genes; therefore, long-term follow-up, especially for young patients, is often needed to establish the correct diagnosis of CP that fully meets the diagnostic criteria. 4 Although, as stated in this article, 1 individuals and their families can benefit from identification of causative genomic variants, it may be too early to recommend exome sequencing to the whole CP population, particularly for interpretating the phenotype-genotype correlation from the perspective of public awareness, family counseling, and rehabilitation optimization.…”

“…Our own work has focused on improving interpretation of electronic fetal monitoring through a developing metric (the Fetal Reserve Index) to improve care and reduce risks. 3,4 Our assessment suggests that about one-third of CP cases are likely of genetic origin, 3,4 a calculation virtually identical to that of Gonzalez-Mantilla. However, these estimates will not satisfy either side in the medicolegal arena.…”

“…We also appreciate the supportive comments by Evans et al, who provided insights into the content and implications of our study and, along with the authors of the accompanying editorial, agree that exome sequencing should be offered to all individuals with CP. 4 As discussed in our article, there are numerous benefits of finding a genetic cause in individuals with CP. Scott M. Myers, MD Christa L. Martin, PhD Andres Moreno-De-Luca, MD, MBA, DABR…”

Implications of Genetic Variants in Cerebral Palsy

“…Gonzalez-Mantilla et al have rigorously collated the literature and reported that whole exome sequencing (WES) studies found abnormalities in 31% of CP cases. In an accompanying editorial, Van Eyk et al suggested that WES should be performed for all CP cases. We completely agree.…”