Longitudinal perspectives on the psychosis spectrum in 22q11.2 deletion syndrome

The prevalence of psychotic disorders in individuals with 22q11.2 Deletion Syndrome (22q11DS) reaches 25–35% in young adulthood and may provide a neurogenetic model for clinical risk of psychotic disorders in the general population. This review focuses on prospective longitudinal studies in 22q11DS, which capture fluctuations in psychosis symptoms over time and may provide insights into potential demographic, clinical, cognitive, and neuroimaging predictors of psychosis-spectrum outcomes in the general population. Findings are compared and contrasted with those from idiopathic psychosis-spectrum populations. Onset of psychotic disorders in 22q11DS can occur over a wide range of ages, peaking in late adolescence. Symptoms may be gradually progressive or episodic in nature, highlighting the importance and challenge of risk and resilience prediction models. Converging results suggest that psychosis-spectrum outcomes in 22q11DS are predicted by lower baseline functioning, higher baseline psychosis-spectrum symptoms, presence of mood disturbance or anxiety, and lower baseline and subsequent decline in global measures of cognition. Predictors of transition to threshold psychotic disorders and ages of onset are similar in idiopathic clinical risk. They also share similarly global cognitive deficits, but not to the same extent as in 22q11DS. While neuroimaging studies in idiopathic clinical risk suggest loss of prefrontal gray matter, there is no consistent evidence yet emerging in the limited literature in 22q11DS. Interventional efforts in 22q11DS aimed at halting progression to psychosis or mitigating outcomes in early psychosis may be best implemented during the adolescent age range. Collaborative longitudinal efforts may help to address existing gaps in our understanding.

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Novel recessive PDZD7 biallelic mutations in two Chinese families with non-syndromic hearing loss

Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous genetic condition. PDZD7 has emerged as a new genetic etiology of ARNSHL. Biallelic mutations in the PDZD7 gene have been reported in two German families, four Iranian families, and a Pakistani family with ARNSHL. The effect of PDZD7 on ARNSHL in other population has yet to be elucidated. Two Chinese ARNSHL families, each of which had two affected siblings, were included in this study. The families underwent target region capture and high-throughput sequencing to analyze the exonic, splice-site, and intronic sequences of 128 genes. Furthermore, 1751 normal Chinese individuals served as controls, and 122 Chinese families segregating with apparent ARNSHL, who had been previously excluded for variants in the common deafness genes GJB2 and SLC26A4, were subjected to screening for candidate mutations. We identified a novel homozygous missense mutation (p.Arg66Leu) and novel compound heterozygous frameshift mutations (p.Arg56fsTer24 and p.His403fsTer36) in Chinese families with ARNSHL. This is the first report to identify PDZD7 as an ARNSHL-associated gene in the Chinese population. Our finding could expand the pathogenic spectrum and strengthens the clinical diagnostic role of the PDZD7 gene in ARNSHL patients.

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Biallelicframeshift mutation in RIN2 in a patient with intellectual disability and cataract, without RIN2 syndrome

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Beyond Down syndrome phenotype: Paternally derived isodicentric chromosome 21 with partial monosomy 21q22.3

Inverted isodicentric chromosome 21 is a rare form of chromosomal rearrangement that may result in trisomy 21; sometimes this rearrangement may also lead to segmental monosomy of the terminal long arm of chromosome 21. In this report, we describe the prenatal diagnosis and neonatal follow-up of a child with a paternally derived, de novo isodicentric chromosome 21 and a concurrent ∼1.2 Mb deletion of the 21q22.3 region [46,XX,idic(21)(q22.3)]. This child presented with unusual phenotype of Down syndrome and additional defects including esophageal atresia and tethered cord syndrome. The resulting phenotype in this infant might be a coalescence of the partial trisomy and monosomy 21, as well as homozygosity for idic (21). The utilization of chromosomal microarray in this case enabled accurate characterization of a rare chromosome abnormality, potentially contributes to future phenotype–genotype correlation and produced evidence for a molecular mechanism underlying this rearrangement.

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Mutations of KIF5C cause a neurodevelopmental disorder of infantile-onset epilepsy, absent language, and distinctive malformations of cortical development

The clinical diagnosis of malformations of cortical development (MCDs) is often challenging due to the complexity of the brain malformation by neuroimaging, the rarity of individual malformation syndromes, and the rapidly evolving genetic landscape of these disorders facilitated with the use of Next Generation Sequencing (NGS) methods. While the clinical and molecular diagnosis of severe cortical malformations, such as classic lissencephaly, is often straightforward, the diagnosis of more subtle and complex types of cortical malformations, such as pachygyria and polymicrogyria (PMG), can be more challenging due to limited knowledge regarding their genetic etiologies. Here, we report two individuals with the same de novo KIF5C mutation who present with subtle MCDs, early onset epilepsy and significant neurodevelopmental and behavioral issues including absent language. Our data, combined with the limited literature on KIF5C mutations, to date, support that KIF5C mutations are associated with a neurodevelopmental disorder characterized by infantile onset epilepsy, and subtle but recognizable types of brain malformations. We also show that the spectrum of KIF5C mutations is narrow, as five out of the six identified individuals have mutations affecting amino acid Glu237. Therefore, the identification of the clinical and neuroimaging features of this disorder may strongly facilitate rapid and efficient molecular diagnosis.

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EMS agency debuts pink ambulance for Breast Cancer Awareness month

Sunstar Paramedics said they have personally been impacted by breast cancer after losing an employee to the disease years ago

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Role of tube size and intranasal compression of the nasotracheal tube in respiratory pressure loss during nasotracheal intubation: a laboratory study.

Role of tube size and intranasal compression of the nasotracheal tube in respiratory pressure loss during nasotracheal intubation: a laboratory study.

BMC Anesthesiol. 2017 Oct 17;17(1):141

Authors: Futagawa K, Takasugi Y, Kobayashi T, Morishita S, Okuda T

Abstract
BACKGROUND: Small nasotracheal tubes (NTTs) and intranasal compression of the NTT in the nasal cavity may contribute to increasing airway resistance. Since the effects of size, shape, and partial compression of the NTT on airway resistance have not been investigated, values of airway resistance with partial compression of preformed NTTs of various sizes were determined.
METHODS: To determine the factors affecting the respiratory pressure loss during the nasotracheal intubation, physical and fluid dynamics simulations were used. The internal minor axes of NTTs in the nasal cavity of intubated patients were measured using dial calipers. In physical and fluid dynamics simulations, pressure losses through the tubular parts, compressed parts, and slip joints of NTTs with internal diameters (IDs) of 6.0, 6.5, 7.0, 7.5, and 8.0 mm were estimated under partial compression.
RESULTS: The median internal minor axes of the 7.0- and 7.5-mm ID NTTs in the nasal cavity were 5.2 (4.3-5.6) mm and 6.0 (4.2-7.0) mm, respectively. With a volumetric air flow rate of 30 L/min, pressure losses through uncompressed NTTs with IDs of 6.0-, 6.5-, 7.0-, 7.5- and 8.0-mm were 651.6 ± 5.7 (6.64 ± 0.06), 453.4 ± 3.9 (4.62 ± 0.04), 336.5 ± 2.2 (3.43 ± 0.02), 225.2 ± 0.2 (2.30 ± 0.00), and 179.0 ± 1.1 Pa (1.82 ± 0.01 cmH2O), respectively; the pressure losses through the slip joints were 220.3 (2.25), 131.1 (1.33), 86.8 (0.88), 57.1 (0.58), and 36.1 Pa (0.37 cmH2O), respectively; and the pressure losses through the curvature of the NTT were 71.6 (0.73), 69.0 (0.70), 64.8 (0.66), 32.5 (0.33), and 41.6 Pa (0.42 cmH2O), respectively. A maximum compression force of 34.1 N increased the pressure losses by 82.0 (0.84), 38.0 (0.39), 23.5 (0.24), 16.6 (0.17), and 9.3 Pa (0.09 cmH2O), respectively.
CONCLUSION: Pressure losses through NTTs are in inverse proportion to the tubes' IDs; greater pressure losses due to slip joints, acute bending, and partial compression of the NTT were obvious in small NTTs. Pressure losses through NTTs, especially in small NTTs, could increase the work of breathing to a greater extent than that through standard tubes; intranasal compression further increases the pressure loss.

PMID: 29041911 [PubMed - in process]

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