Novel Homozygous TTI2 Variant Causing Autosomal Recessive Syndromic Intellectual Disability and Primary Microcephaly from Pakistan: A Case Report (Exome Report).

We describe a male patient with a novel TTI2 variant, which has not been previously associated with a human phenotype. His features include intellectual disability, primary microcephaly, delayed psychomotor development, speech delay, short stature, dysmorphic facial features, esotropia, kyphoscoliosis, and behavior abnormalities (Figure). Next generation sequencing revealed autosomal recessive TTI2 variant with uncertain significance, denoted as c.21_22insAAGCGCTCTG (p.Glu8Lysfs × 12). TTI2 encodes a regulator of DNA damage response and helps maintain steady levels of the PIKK family of protein kinases. No disease-causing variants in other genes potentially linked to his clinical presentation were identified. We report a novel loss-of-function homozygous variant in TTI2 that leads to syndromic intellectual disability and primary microcephaly.

The mid-term and long-term effects of tourniquet use in total knee arthroplasty: systematic review.

PURPOSE: A tourniquet is routinely used during total knee arthroplasty (TKA) to reduce intra-operative hemorrhage, though surgery without a tourniquet is becoming popular. To address concerns about the effect of blood at cement interfaces on long-term implant stability, we conducted a systematic review among patients undergoing total knee arthroplasty to determine if TKA with a tourniquet, compared to TKA without a tourniquet or with reduced tourniquet duration, is associated with better mid-term and long-term implant stability. METHODS: A literature search was conducted without language restriction in PubMed, Cochrane database and Web of Science from conception to 17th March, 2021. Prospective cohorts, randomized and observational, that compared tourniquet use with a control group, followed patients for 3 months or more and reported outcomes concerning implant stability, limb function, pain and inflammation. Article selection, quality assessment according to the Revised Cochrane risk assessment scale and Newcastle Ottawa Scale, and data extraction were conducted in duplicate. PROSPERO: CRD42020179020. RESULTS: The search yielded 4868 articles, from which 16 randomized controlled trials (RCT) and four prospective cohort studies, evaluating outcomes of 1884 knees, were included. Eleven RCTs were evaluated to be low overall risk of bias, five RCTs had some concerns and four cohort studies were good quality. Few studies showed benefits of tourniquet use in mid-term implant stability (1/6), pain (1/11) and limb inflammation (1/5), and long-term implant stability (1/1). One study reported a significantly improved range of motion (1/14) while another reported significantly reduced quadriceps strength (1/6) in the tourniquet group. The remaining studies reported non-significant effect of tourniquet use. CONCLUSION: Although few studies indicated benefits of tourniquet use in mid-term pain, limb inflammation, implant loosening and function, and long-term implant loosening, the majority of studies report no significant advantage of tourniquet use in total knee arthroplasty.

MYORG-related disease is associated with central pontine calcifications and atypical parkinsonism.

OBJECTIVE: To identify the phenotypic, neuroimaging, and genotype-phenotype expression of MYORG mutations. METHODS: Using next-generation sequencing, we screened 86 patients with primary familial brain calcification (PFBC) from 60 families with autosomal recessive or absent family history that were negative for mutations in SLC20A2, PDGFRB, PDGBB, and XPR1. In-depth phenotyping and neuroimaging investigations were performed in all cases reported here. RESULTS: We identified 12 distinct deleterious MYORG variants in 7 of the 60 families with PFBC. Overall, biallelic MYORG mutations accounted for 11.6% of PFBC families in our cohort. A heterogeneous phenotypic expression was identified within and between families with a median age at onset of 56.4 years, a variable combination of parkinsonism, cerebellar signs, and cognitive decline. Psychiatric disturbances were not a prominent feature. Cognitive assessment showed impaired cognitive function in 62.5% of cases. Parkinsonism associated with vertical nuclear gaze palsy was the initial clinical presentation in 1/3 of cases and was associated with central pontine calcifications. Cerebral cortical atrophy was present in 37% of cases. CONCLUSIONS: This large, multicentric study shows that biallelic MYORG mutations represent a significant proportion of autosomal recessive PFBC. We recommend screening MYORG mutations in all patients with primary brain calcifications and autosomal recessive or negative family history, especially when presenting clinically as atypical parkinsonism and with pontine calcification on brain CT.