Characterization of patients referred for non-specific intellectual disability testing: the importance of autosomal genes for diagnosis.

Genetic testing for non-specific intellectual disability (ID) presents challenges in daily clinical practice. Historically, the focus of the genetic elucidation of non-specific ID has been on genes on the X chromosome, and recent research has brought attention to the growing contribution of autosomal genes. In addition, next-generation sequencing (NGS) has greatly improved the ability to simultaneously analyze multiple genetic loci, making large panel testing a practical approach to testing for non-specific ID. We performed NGS analysis of a total of 90 genes implicated in non-specific ID. The 90 genes included 56 X-linked genes and 34 autosomal genes. Pathogenic variants were identified in 11 of 52 (21%) patient samples. Nine of the eleven cases harbored mutations in autosomal genes including AP4B1, STXB1, SYNGAP1, TCF4 and UBE3A. Our mutation-positive cases provide further evidence supporting the prevalence of autosomal mutations in patients referred for non-specific ID testing and the utility of their inclusion in multi-gene panel analysis.

Low-level constitutional mosaicism of a de novoBRCA1 gene mutation.

BACKGROUND: Pathogenic BRCA1 mutations are usually inherited. Constitutional low-level BRCA1 mosaicism has never been reported. METHODS: Next-generation sequencing (NGS) of cancer gene panel of germline and tumour DNA in a patient with early onset, triple-negative breast cancer. RESULTS: Constitutional de novo mosaicism (5%) for a pathogenic (c.1953dupG; p.Lys652Glufs*21) BRCA1mutation was detected in leukocytes, buccal tissue and normal breast tissue DNA, with ∼50% mutation in tumorous breast tissue. CONCLUSION: This is the first reported case of low-level, multiple tissue, constitutional mosaicism in BRCA1, and highlights the need to consider deep sequencing in affected individuals clinically suspected of having cancer predisposition whose tumours display a BRCA mutation.

Exome sequencing and the genetics of intellectual disability.

Exome sequencing has greatly impacted the speed at which new disease genes are identified. In the last year alone, six studies have used exome sequencing to identify new genes involved in intellectual disability, a genetically heterogeneous condition affecting 1-3% of the population. These studies encompass the full gamut of modes of inheritance and phenotypic presentation, including syndromic and non-syndromic conditions, sporadic and familial cases, and dominant and recessive inheritance patterns. Because different disease presentations require different approaches to gene discovery, studies of intellectual disability provide a nearly comprehensive showcase of strategies for exome-driven gene discovery. Despite these successes, the etiology of ~60% of cases of intellectual disability remains unknown. The application of exome sequencing to the clinical diagnosis of intellectual disability in the near future will ultimately reduce the number of idiopathic cases and provide a rich source of sequence variation for the identification of new intellectual disability genes.

[Noninvasive monitoring of the hepatocellular carcinoma growth by the method of 1H and 23Na nuclear magnetic resonance].

Using diffusion weighted 1H, single-quantum 23Na and triple-quantum-filtered 23Na magnetic resonance imaging water apparent diffusion coefficient (ADC), total tissue Na+ and intracellular Na+ were monitored in hepatocellular carcinoma (HCC) in rats and in the surrounding liver tissue. The tumor water ADC was approximately 50% higher compared to the nearby healthy liver tissue but did not increase during 28 days of tumor growth (double time 3.9 days). The HCC growth was associated with an increase in both total tissue and intracellular 23Na signal intensity especially after 21 days post-cell inoculation reflecting possible changes in extracellular space and in intracellular ionic metabolism.

Magnetic resonance imaging of the humpback scaphoid: the technique and a mathematical performance evaluation.

Surgical treatment of scaphoid nonunion and malunion with excessive intrascaphoid angulation (humpback deformity) usually involves a bone graft that is intended to correct the deformity. The volar bone graft length determines the degree of angular correction and scaphoid elongation. It is recommended that the length of the graft be determined by careful preoperative measurement of the deformity. Previous imaging techniques are inherently limited. The present paper describes a technique using three-dimensional magnetic resonance imaging. Scaphoid fracture angulation is calculated from measurements of comparable sagittal slices of the patient's fractured and normal scaphoid. Optimal bone graft length is determined by using simple trigonometric principles. Magnetic resonance imaging provides additional important information regarding vascularity of the proximal pole and the status of the periscaphoid ligaments and hyaline cartilage. Mathematical performance evaluation indicates that this technique is a promising method for planning reconstructive surgery of the scaphoid.

A randomized prospective study of posterolateral lumbar fusion. Outcomes with and without pedicle screw instrumentation.

STUDY DESIGN: A prospective evaluation of the clinical and radiographic outcomes of 71 patients who underwent lumbar fusion, with or without transpedicular instrumentation. The patients completed a questionnaire that determined pain relief, medication use, return to work, and overall satisfaction with surgery. OBJECTIVES: To explore the effect, if any, of instrumentation on the outcome of lumbar fusion surgery, according to reports of the patients, and whether there is a correlation between the radiographic determination of a solid fusion and the same patient-reported outcome. SUMMARY OF BACKGROUND DATA: The literature on this topic reports pseudarthrosis rates from 0% to 57% and good to excellent results from 56% to 95%. These studies provide no clear-cut recommendations concerning the effect of added lumbar instrumentation on patient-reported outcome in a prospective manner using concurrent control subjects. METHODS: The patients were randomized to groups with and without instrumentation after deciding to undergo a lumbar fusion and consenting to enter the study. Radiographs were obtained and questionnaires filled out at 6 weeks, 6 months, 1 year, and 2 years after surgery. RESULTS: There was no statistical difference in patient-reported outcome between the two groups. There was a slight nonsignificant trend toward increased radiographic fusion rate in the group with instrumentation that did not correlate with an increased patient-reported improvement rate. CONCLUSIONS: These results do not provide data that indicate a benefit in outcome from added instrumentation in elective lumbar fusions.

The utility of spine surgery instrumentation in decompression of the suprascapular notch.

Decompression of the suprascapular nerve through the posterior approach minimizes muscular damage and postoperative scar. The difficulty with this approach is that the depth of the exposure makes operating around the delicate structures of the suprascapular artery and nerve challenging. Spine surgery instrumentation is very helpful in circumventing this problem. Once exposure is achieved, a nerve root retractor is used to retract the suprascapular artery and vein. A number 2 Woody Woodson elevator is used to protect the suprascapular nerve. A number 1 or 2 Kerrison rongeur is then used to resect the suprascapular ligament. The Kerrison rongeur is a particularly useful instrument if an ossified ligament is encountered.

Trigger finger: the effect of partial release of the first annular pulley on triggering.

A prospective, randomized study was performed on 19 patients, in whom the proximal, middle, or distal third of the first annular pulley was divided to determine if a specific portion of the first annular pulley was responsible for the clinical triggering associated with restrictive flexor tenosynovitis. In all 19 patients, a partial resection of the first annular pulley resulted in continued clinical triggering with active digital flexion. At this point, a standard complete first annular pulley release was performed, with resolution of clinical triggering of the involved digit in all patients. We conclude that there is no "critical third" of the first annular pulley responsible for clinical digital triggering.

Ulnar styloid impaction syndrome.

A series of 8 patients each with an excessively long ulnar styloid that was impacting the triquetrum, causing chondromalacia, synovitis, and pain, is presented. Four patients developed symptoms as a result of an injury and 4 had no definable acute precipitating injury. The average age at the time of surgery was 34 years. There were 3 male and 5 female patients. The average follow-up period was 34 months. All patients were treated by open partial ulnar styloidectomy. Outcome was evaluated clinically and by means of patient questionnaire and radiographs. Pain decreased from a preoperative average score of 3.5 to a postoperative average score of 1.3, which equates to mild pain requiring no medication. All but 1 patient returned to their previous employment unrestricted. The average preoperative ulnar styloid length was 7.4 mm and the average ulnar styloid process index was 0.41, which is almost twice normal. There were no complications. It is likely that an excessively long ulnar styloid has important implications for the kinematics of the lunatotriquetral interval. Details of the diagnosis of this condition, including a new provocative test, and operative management are discussed.

Symptomatic adhesions of the index interosseous-lumbrical tendons: a case report.

A patient presented with activity-related pain in the distal radial palm. Surgical exploration revealed adhesion of the index lumbrical tendon to the metacarpophalangeal joint capsule and the tendon of the first dorsal interosseous. Symptoms were relieved by lysis of adhesions and immediate postoperative motion therapy.

CHILD syndrome: analysis of abnormal keratinization and ultrastructure.

A new patient with CHILD syndrome (congenital hemidysplasia, ichthyosiform erythroderma, and limb defects), the thirtieth in the literature, was observed for over three years. Initially, the right-sided lesion spared the breast area. At 10 months of age the trunk lesion extended to cover the entire area of the right chest. At age 20 months the patient developed linear, bandlike, keratotic, brown-black lesions on her left thigh that subsided within six weeks, leaving a slight hyperpigmentation. This patient was studied by routine histologic methods as well as with markers of keratinization and electron microscopy. In hematoxylin and eosinstained sections, parakeratosis and orthokeratosis alternated. In some parakeratotic areas, large granular cells, and in others, ghost granular cells, were present. The latter showed basophilic cytoplasm, and palestaining or vacuolated nucleus and were seen either above the normal granular layer or without it. Although regional variations existed, basal cell-type keratins as recognized by AE1 continued to be expressed in suprabasal layers. Filaggrin- and involucrin-positive layers were expanded, particularly the latter, down to the lower prickle cell layer. Ultrastructurally, numerous lamellar or membranous structures were found in upper layers of the epidermis, both intracellulary and intercellularly. Normal cementsomes coexisted with these abnormal lamellar structures, and it was thought that the latter represent modified cementsomes because the discharge of those from the cell periphery was often detected.

Diffuse neonatal hemangiomatosis: a new constellation of findings.

Diffuse neonatal hemangiomatosis is a rare, frequently fatal disease characterized by multiple cutaneous and visceral hemangiomas. The skin, liver, lungs, intestines, and central nervous system are the most commonly affected organs. Death can result from high-output cardiac failure as a result of arteriovenous shunting. In this report we present a new constellation of findings in a patient with diffuse neonatal hemangiomatosis, namely, an absent corpus callosum, ectopia cordis (sternal agenesis) with median abdominal raphe, and tricuspid atresia.

Necrotizing myonecrosis and polymicrobial sepsis. The role of adjunctive hyperbaric oxygen.

A 19-year-old man, who was involved in a motorcycle accident, sustained a combined bony and vascular injury to his right lower extremity that required emergency surgery. Postoperatively, the patient developed a life-threatening, necrotizing, soft-tissue infection and sepsis. Hyperbaric oxygen therapy was used with surgery and antibiotics to control this rapidly progressive infection and to limit the extent of debridement needed. It was found to reverse the patient's deteriorating status and to halt the progression of the necrotizing infection. The scientific evidence for the use of hyperbaric oxygen in such cases is discussed.