Sahar Saleem

INTRODUCTION: Pathogenic variants in the PIEZO family member 2 () gene are known to cause Gordon syndrome (GS), Marden-Walker syndrome (MWS), and distal arthrogryposis type 5 (DA5). Out of these, MWS has a recognizable phenotype that can be discerned easily, but the distinction between GS and DA5 is less evident. Few children with pathogenic variants have been reported to show posterior fossa anomalies.

METHODS AND RESULTS: By candidate gene targeting guided by proper clinical evaluation and neuroimaging findings, a patient with classic MWS harboring a de novo novel variant (c.8237G>A, p.W2746*) in the C-terminal region of PIEZO2 was identified. In addition, another girl with the typical clinical features of GS is also described carrying the most prevalent reported variant (c.8057G>A, p.R2686H) in . The brain MRI of the 2 patients showed Dandy-Walker malformation (DWM). Diffusion tensor imaging visualized anteroposterior and downward aligned thin middle cerebellar peduncle. The association of DWM with arthrogryposis in the presence of variants remains quite interesting and provides more evidence that PIEZO2 plays a role in the development of hindbrain although the underlying mechanism remains unclear. Moreover, the 2 girls had distinct foot patterning in the form of shortening of the first and fifth toes.

CONCLUSION: Phenotype analysis and a comprehensive review of the literature strongly support the previously published data and corroborate the evidence that heterozygous related disorders represent a continuum with overlapping phenotypic features.

The mummy of King Amenhotep I (18th Dynasty c.1525-1504 BC) was reburied by the 21st Dynasty priests at Deir el-Bahari Royal Cache. In 1881 the mummy was found fully wrapped and was one of few royal mummies that have not been unwrapped in modern times. We hypothesized that non-invasive digital unwrapping using CT would provide insights on the physical appearance, health, cause of death, and mummification style of the mummy of King Amenhotep I. We examined the mummy with CT and generated two- and three-dimensional images for the head mask, bandages, and the virtually unwrapped mummy. CT enabled the visualization of the face of Amenhotep I who died around the age of 35 years. The teeth had minimal attrition. There was no CT evidence of pathological changes or cause of death. The body has been eviscerated a vertical left flank incision. The heart is seen in the left hemithorax with an overlying amulet. The brain has not been removed. The mummy has 30 amulets/jewelry pieces including a beaded metallic (likely gold) girdle. The mummy suffered from multiple postmortem injuries likely inflicted by tomb robbers that have been likely treated by 21st Dynasty embalmers. These included fixing the detached head and neck to the body with a resin-treated linen band; covering a defect in the anterior abdominal wall with a band and placing two amulets beneath; placement of the detached left upper limb beside the body and wrapping it to the body. The transversely oriented right forearm is individually wrapped, likely representing the original 18th Dynasty mummification and considered the first known New Kingdom mummy with crossed arms at the chest. The head mask is made of cartonnage and has inlaid stone eyes. The digital unwrapping of the mummy of Amenhotep I using CT sets a unique opportunity to reveal the physical features of the King non-invasively, understand the mummification style early in the 18th Dynasty, and the reburial intervention style by 21st Dynasty embalmers. This study may make us gain confidence in the goodwill of the reburial project of the Royal mummies by the 21st dynasty priests.