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Doublecortin, encoded by the DCX gene, plays a crucial role in the neuronal migration process during brain development. Pathogenic variants of the DCX gene are the major causes of the \"lissencephaly (LIS) spectrum\", which comprehends a milder phenotype like Subcortical Band Heterotopia (SBH) in heterozygous female subjects. We performed targeted sequencing in three unrelated female cases with SBH. We identified three DCX-related variants: a novel missense (c.601A>G: p.Lys201Glu), a novel nonsense (c.210C>G: p.Tyr70*), and a previously identified nonsense (c.907C>T: p.Arg303*) variant. The novel c.601A>G: p.Lys201Glu variant shows a mother-daughter transmission pattern across four generations. The proband exhibits focal epilepsy and achieved seizure freedom with a combination of oxcarbazepine and levetiracetam. All other affected members have no history of epileptic seizures. Brain MRIs of the affected members shows predominant fronto-central SBH with mixed pachygyria on the overlying cortex. The two nonsense variants were identified in two unrelated probands with SBH, severe drug-resistant epilepsy and intellectual disability. These novel DCX variants further expand the genotypic-phenotypic correlations of lissencephaly spectrum disorders. Our documented phenotypic descriptions of three unrelated families provide valuable insights and stimulate further discussions on DCX-SBH cases.

Subcortical band heterotopia (SHB) is a rare severe brain developmental malformation caused by deficient neuronal migration during the development of cerebral cortex. Here, a human induced pluripotent stem cell (iPSCs) line was established from a 4-year-1-month-old girl with SHB carrying a heterozygous mutation (c.568A > G, p.K190E) in DCX. The generated iPSC line showed the ability to differentiate into three lineages in vitro and was confirmed by pluripotency markers and the original gene mutation.

The ILAE Neuroimaging Task Force publishes educational case reports that highlight basic aspects of neuroimaging in epilepsy consistent with the ILAE\'s educational mission. Subcortical laminar heterotopia, also known as subcortical band heterotopia (SBH) or \"double cortex,\" is an intriguing and rare congenital malformation of cortical development. SBH lesions are part of a continuum best designated as agyria-pachygyria-band-spectrum. The malformation is associated with epilepsy that is often refractory, as well as variable degrees of developmental delay. Moreover, in an increasing proportion of cases, a distinct molecular-genetic background can be found. Diagnosing SBH can be a major challenge for many reasons, including more subtle lesions, and \"non-classic\" or unusual MRI-appearances. By presenting an illustrative case, we address the challenges and needs of diagnosing and treating SBH patients in epilepsy, especially the value of high-resolution imaging and specialized MRI-protocols.

About 50% of individuals with developmental and epileptic encephalopathies (DEEs) are unsolved following genetic testing. Deep intronic variants, defined as >100 bp from exon-intron junctions, contribute to disease by affecting the splicing of mRNAs in clinically relevant genes. Identifying deep intronic pathogenic variants is challenging and resource intensive, and interpretation is difficult due to limited functional annotations. We aimed to identify deep intronic variants in individuals suspected to have unsolved single gene DEEs. In a research cohort of unsolved cases of DEEs, we searched for children with a DEE syndrome predominantly caused by variants in specific genes in >80% of described cases. We identified two children with Dravet syndrome and one individual with classic lissencephaly. Multiple sequencing and bioinformatics strategies were employed to interrogate intronic regions in SCN1A and PAFAH1B1. A novel de novo deep intronic 12 kb deletion in PAFAH1B1 was identified in the individual with lissencephaly. We showed experimentally that the deletion disrupts mRNA splicing, which results in partial intron retention after exon 2 and disruption of the highly conserved LisH motif. We demonstrate that targeted interrogation of deep intronic regions using multiple genomics technologies, coupled with functional analysis, can reveal hidden causes of unsolved monogenic DEE syndromes. PLAIN LANGUAGE SUMMARY: Deep intronic variants can cause disease by affecting the splicing of mRNAs in clinically relevant genes. A deep intronic deletion that caused abnormal splicing of the PAFAH1B1 gene was identified in a patient with classic lissencephaly. Our findings reinforce that targeted interrogation of deep intronic regions and functional analysis can reveal hidden causes of unsolved epilepsy syndromes.

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Second-generation headless compression screws (HCSs) are commonly used for the fixation of small bones and articular fractures. However, there is a lack of biomechanical data regarding the application of such screws to radial head fractures. This study evaluated the mechanical properties of the fixation of radial head fractures using a single oblique HCS compared with those obtained using a standard locking radial head plate (LRHP) construct and a double cortical screw (DCS) construct. Radial synbone models were used for biomechanical tests of HCS, LRHP, and DCS constructs. All specimens were first cyclically loaded and then loaded to failure. The stiffness for the LRHP group was significantly higher than that for the other two groups, and that for the HCS group was significantly higher than that for the DCS group. The LRHP group had the greatest strength, followed by the HCS group and then the DCS group. The HCS construct demonstrated greater fixation strength than that of the commonly used cortical screws, although the plate group was the most stable. The present study revealed the feasibility of using a single oblique HCS, which has the advantages of being buried, requiring limited wound exposure, and having relatively easy operation, for treating simple radial head fractures.

OBJECTIVE: A double cortical button technique for ulnar collateral ligament reconstruction (UCLR) has advantages including significant control over graft tensioning, less concern about graft length, and minimized risk of bone tunnel fracture compared with traditional UCLR techniques. This double cortical button technique was recently found to be noninferior in mechanical performance to the traditional docking technique regarding joint strength, joint stiffness, and graft strain. However, clinical outcomes have not been compared between these UCLR techniques. Therefore, the purpose of this study was to determine whether baseball players who underwent UCLR with a double cortical button (double button) technique have similar return-to-sport (RTS) outcomes to baseball players who underwent UCLR with the traditional docking (docking) technique.
METHODS: Baseball players who underwent primary UCLR from 2011 to 2020 across 2 institutions were identified. Included patients were contacted to complete a follow-up survey evaluating reoperations, RTS, and functional outcome scores. Functional outcome surveys include the Kerlan-Jobe Orthopaedic Clinic score, the Conway-Jobe score, the Andrews-Timmerman elbow score, and the Single Assessment Numeric Evaluation score.
RESULTS: Overall, 78 male baseball players (age: 18.9 ± 2.4 years) with an average follow-up of 3.1 ± 2.4 years were evaluated, with 73 of the players being baseball pitchers. Players in the double button group more frequently received palmaris longus autografts (78% vs. 30%) and less frequently received gracilis autografts (22% vs. 58%) compared with players in the docking group (P = .001); however, all other demographic factors were similar between the groups. All players in the double button group were able to RTS in 11.1 ± 2.6 months, whereas 96% of players in the docking group were able to RTS in 13.5 ± 3.4 months (P > .05). All postoperative outcomes and patient-reported outcomes were statistically similar between the groups and remained similar after isolating pitchers only and after separating partial-thickness from full-thickness UCL tears (all P > .05).
CONCLUSIONS: RTS and other postoperative outcomes may be similar between baseball players who underwent UCLR with the double button technique and the docking technique. Although future research may be necessary to strengthen clinical recommendations, these findings provide the first clinical outcomes in light of a recent cadaveric study finding similar elbow strength, joint stiffness, and graft strain compared with the docking technique.

OBJECTIVE: To explore the clinical characteristics and genetic basis for a child with X-linked lissencephaly with abnormal genitalia (XLAG).
METHODS: A child with XLAG who had presented at the Third Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to high-throughput sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the result was analyzed by using bioinformatic software.
RESULTS: The child was found to have harbored a hemizygous c.945_948del variant in exon 2 of the ARX gene, which as a frameshifting variant has resulted in a truncated protein. His mother was found to be heterozygous for the variant, whilst his father was of wild type. The variant was unreported previously.
CONCLUSIONS: The hemizygous c.945_948del variant of the ARX gene probably underlay the XLAG in this patient. Above finding has provided a basis for the diagnosis and genetic counseling for this family.

Lissencephaly type 10 is a recently reported condition characterized by posterior predominant abnormalities in gyration with associated seizures, developmental delays or intellectual disability. We report a boy who presented at 5 years of age with epilepsy and developmental delays. His family history was notable for epilepsy in two prior generations associated with variable developmental and cognitive impact. Exome sequencing identified a novel missense variant in CEP85L [NM_001042475.2; c.196A>G, p.(Thr66Ala)] which segregated in four affected family members across three generations. Brain imaging of the proband demonstrated a posterior lissencephaly pattern with pachygyria, while other affected family members demonstrated a similar subcortical band heterotopia. This report expands the phenotypic spectrum of this rare disorder by describing a novel variant in CEP85L in a family with variable clinical and neuroimaging findings.