The intracranial and posterior cranial fossa volumes and volume fractions in children: A stereological study [Los volúmenes de la fosa craneal intracraneal y posterior y las fracciones de volumen en los niños: Un estudio estereológico]

The size of intracranial cavity (IC) and posterior cranial fossa (PCF) plays an important role in the pathophysiology of various disorders. In this study, we aimed at establishing normal volume data of the IC and PCF in Turkish population according to age and sex by using stereological method. This study was carried out retrospectively on 339 individuals (168 females and 171 males) between 0 and 18 years old with no medical or neurological disorders that affected the skeletal morphology of the cranial cavity. Volumetric estimations were determined on computed tomography (CT) images using point-counting approach of stereological methods. Intracranial volume (ICV) and posterior cranial fossa volume (PCFV) were increased with age in both sexes. They reached adult dimensions at 5 years of age during the teenage years. According to sex; the mean ICV and PCFV were 1594.51±245.57cm3 and 244.89±53.86 cm3 in males, 1456.34±241.85 cm3 and 228.24±41.38 cm3 in females, respectively. Generally, significant differences were determined in ICV and PCFV according to sex after they reached maximum growth period. According to age the volume ratios of PCF to IC was ranged from 13.03 to 17.48 in males and 12.06 to 18.54 in females. This study demonstrated that these volume ratios could help the physician for both patient selections for surgery, and for the assessment of any surgical technique used to treatment of PCF malformations. However current study revealed that point counting method can produce accurate volume estimations and is effective in determining volume estimation of IC and PCF. © 2017, Universidad de la Frontera. All rights reserved

Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction.

Pediatric-onset ataxias often present clinically as developmental delay and intellectual disability, with prominent cerebellar atrophy as a key neuroradiographic finding. Here we describe a new clinically distinguishable recessive syndrome in 12 families with cerebellar atrophy together with ataxia, coarsened facial features and intellectual disability, due to truncating mutations in the sorting nexin gene SNX14, encoding a ubiquitously expressed modular PX domain-containing sorting factor. We found SNX14 localized to lysosomes and associated with phosphatidylinositol (3,5)-bisphosphate, a key component of late endosomes/lysosomes. Patient-derived cells showed engorged lysosomes and a slower autophagosome clearance rate upon autophagy induction by starvation. Zebrafish morphants for snx14 showed dramatic loss of cerebellar parenchyma, accumulation of autophagosomes and activation of apoptosis. Our results characterize a unique ataxia syndrome due to biallelic SNX14 mutations leading to lysosome-autophagosome dysfunction

Biallelic Mutations in Snx14 Cause A Syndromic Form of Cerebellar Atrophy and Lysosome-Autophagosome Dysfunction

Pediatric-onset ataxias often present clinically with developmental delay and intellectual disability, with prominent cerebellar atrophy as a key neuroradiographic finding. Here we describe a novel clinically distinguishable recessive syndrome in 12 families with cerebellar atrophy together with ataxia, coarsened facial features and intellectual disability, due to truncating mutations in sorting nexin 14 (SNX14), encoding a ubiquitously expressed modular PX-domain-containing sorting factor. We found SNX14 localized to lysosomes, and associated with phosphatidyl-inositol (3,5)P2, a key component of late endosomes/lysosomes. Patient cells showed engorged lysosomes and slower autophagosome clearance rate upon starvation induction. Zebrafish morphants showed dramatic loss of cerebellar parenchyma, accumulated autophagosomes, and activation of apoptosis. Our results suggest a unique ataxia syndrome due to biallelic SNX14 mutations, leading to lysosome-autophagosome dysfunction.PubMedWo