Fetal akinesia deformation sequence with pontocerebellar hypoplasia, and migration and gyration defects

Meghan Elizabeth Kapp,Hilary Highfield Nickols,Pamela Lyle

doi:10.4322/acr.2021.323

Abstract

ABSTRACTFetal akinesia deformation sequence (FADS), or Pena-Shokeir phenotype is a constellation of deformational changes resulting from decreased or absent fetal movement, and include arthrogryposis, and craniofacial and central nervous system anomalies. We report an autopsy case of a 36-6/7week female neonate with a normal female karyotype and chromosome microarray demonstrating findings consistent with FADS. We provide a detailed examination of the severe and complex central nervous system abnormalities, including marked pontocerebellar hypoplasia and cortical and cerebellar migration and gyration defects. This case represents a rare detailed examination of the central nervous system of a patient with FADS.

Highlights

Fetal akinesia deformation sequence (FADS) or Pena-Shokeir phenotype (PSP) is a lethal condition first described in 1974 by Pena and Shokeir.[1]
Skeletal muscle represented by neck strap muscles, lower extremity muscle, and intercostal muscle showed no significant histopathologic change. The neuropathology of this late preterm female newborn with FADS who died within hours of delivery is complex with combined malformative and acquired vascular-related abnormalities, evidenced by pachygyration and dysplasia of the cerebral cortex as well as the cerebello-ponto-olivary circuitry, and chronic/remote periventricular leukomalacia (PVL) in the cerebral white matter, respectively
PCH1 is associated with anterior horn cell loss and PCH2 and PCH7 with “progressive atrophy” of the cerebral cortex, neither of which are features of our case

Summary

INTRODUCTION

Fetal akinesia deformation sequence (FADS) or Pena-Shokeir phenotype (PSP) is a lethal condition first described in 1974 by Pena and Shokeir.[1]. Beginning at 18 5/7 gestational weeks, the prenatal ultrasounds demonstrated multiple fetal anomalies including absent corpus callosum, severe ventriculomegaly, arthrogryposis with bilateral talipes, and kyphoscoliosis. The midbrain and pons were both hypoplastic and the cerebellum was hypoplastic overall with the vermis and lateral hemispheres present; no cerebellar cysts were identified. While the medial part of the lateral hemisphere contains folia, they appear small in size. In these folia, the external granular layer was approximately 8 cells thick (age-appropriate), and the Purkinje cells and internal granular cells were present in proper laminated formation. Neurons, were present in the cerebellar white matter (Figure 4D). Skeletal muscle represented by neck strap muscles, lower extremity muscle, and intercostal muscle showed no significant histopathologic change

Findings

DISCUSSION

CONCLUSION