St. Luke's Children's Hospital

Recent work has established that heterozygous germline GATA2 mutations predispose carriers to familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), "MonoMAC" syndrome, and DCML deficiency. Here, we describe a previously unreported MDS family carrying a missense GATA2 mutation (p.Thr354Met), one patient with MDS/AML carrying a frameshift GATA2 mutation (p.Leu332Thrfs*53), another with MDS harboring a GATA2 splice site mutation, and 3 patients exhibiting MDS or MDS/AML who have large deletions encompassing the GATA2 locus. Intriguingly, 2 MDS/AML or "MonoMAC" syndrome patients with GATA2 deletions and one with a frameshift mutation also have primary lymphedema. Primary lymphedema occurs as a result of aberrations in the development and/or function of lymphatic vessels, spurring us to investigate whether GATA2 plays a role in the lymphatic vasculature. We demonstrate here that GATA2 protein is present at high levels in lymphatic vessel valves and that GATA2 controls the expression of genes important for programming lymphatic valve development. Our data expand the phenotypes associated with germline GATA2 mutations to include predisposition to primary lymphedema and suggest that complete haploinsufficiency or loss of function of GATA2, rather than missense mutations, is the key predisposing factor for lymphedema onset. Moreover, we reveal a crucial role for GATA2 in lymphatic vascular development.

BACKGROUND: Osteochondritis dissecans (OCD) is a disorder of subchondral bone and articular cartilage whose incidence in children is not clearly known. PURPOSE: The purpose of this study was to assess the demographics and epidemiology of OCD of the knee in children. STUDY DESIGN: Descriptive epidemiology study. METHODS: A retrospective chart review of an integrated health system was performed on patients with OCD of the knee aged 2 to 19 years from 2007 to 2011, with over 1 million patients in this cohort. Lesion location, laterality, and all patient demographics were recorded. The incidence of OCD was determined for the group as a whole and by sex and age group (2-5 years, 6-11 years, and 12-19 years). Patient differences based on age, sex, and ethnicity were analyzed, and using multivariable logistic regression models, associations between age, sex, ethnicity, and diagnosis of OCD of the knee were evaluated. RESULTS: One hundred ninety-two patients with 206 OCD lesions of the knee fit the inclusion criteria. No OCD lesion of the knee was found in 2- to 5-year-old children. One hundred thirty-one (63.6%) lesions were in the medial femoral condyle, 67 (32.5%) were in the lateral femoral condyle, 96 (50.0%) lesions were right sided, 82 (42.7%) were left sided, and 14 (7.3%) were bilateral. The incidence of patients with OCD of the knee aged 6 to 19 years was 9.5 per 100,000 overall and 15.4 and 3.3 per 100,000 for male and female patients, respectively. Those aged 12 to 19 years represented the vast majority of OCD, with an incidence of 11.2 per 100,000 versus 6.8 per 100,000 for those aged 6 to 11 years. For those aged 6 to 11 and 12 to 19 years, female patients had an incidence of 2.3 and 3.9 per 100,000, respectively, while male patients had an incidence of 11.1 and 18.1 per 100,000, respectively. Multivariable logistic regression analysis revealed a 3.3-fold increased risk of OCD of the knee in patients aged 12 to 19 years compared with those aged 6 to 11 years (P < .001; 95% confidence interval [CI], 2.37-4.48), and male patients had 3.8 times a greater risk of OCD of the knee than female patients (P < .001; 95% CI, 2.71-5.41). Based on race and ethnicity, blacks had the highest odds ratio of OCD of the knee compared with all other ethnic groups. CONCLUSION: In this population-based cohort study of pediatric OCD of the knee, male patients had a much greater incidence of OCD and almost 4 times the risk of OCD compared with female patients. Also, patients aged 12 to 19 years had 3 times the risk of OCD of the knee as compared with 6- to 11-year-old children.

OBJECTIVE: Recent reports have described single individuals with neurodevelopmental disability (NDD) harboring heterozygous KCNQ3 de novo variants (DNVs). We sought to assess whether pathogenic variants in KCNQ3 cause NDD and to elucidate the associated phenotype and molecular mechanisms. METHODS: Patients with NDD and KCNQ3 DNVs were identified through an international collaboration. Phenotypes were characterized by clinical assessment, review of charts, electroencephalographic (EEG) recordings, and parental interview. Functional consequences of variants were analyzed in vitro by patch-clamp recording. RESULTS: Eleven patients were assessed. They had recurrent heterozygous DNVs in KCNQ3 affecting residues R230 (R230C, R230H, R230S) and R227 (R227Q). All patients exhibited global developmental delay within the first 2 years of life. Most (8/11, 73%) were nonverbal or had a few words only. All patients had autistic features, and autism spectrum disorder (ASD) was diagnosed in 5 of 11 (45%). EEGs performed before 10 years of age revealed frequent sleep-activated multifocal epileptiform discharges in 8 of 11 (73%). For 6 of 9 (67%) recorded between 1.5 and 6 years of age, spikes became near-continuous during sleep. Interestingly, most patients (9/11, 82%) did not have seizures, and no patient had seizures in the neonatal period. Voltage-clamp recordings of the mutant KCNQ3 channels revealed gain-of-function (GoF) effects. INTERPRETATION: Specific GoF variants in KCNQ3 cause NDD, ASD, and abundant sleep-activated spikes. This new phenotype contrasts both with self-limited neonatal epilepsy due to KCNQ3 partial loss of function, and with the neonatal or infantile onset epileptic encephalopathies due to KCNQ2 GoF. ANN NEUROL 2019;86:181-192.

A concern in the intervention with sexually abused children is the support of their nonoffending guardians after disclosure of the abuse. Approximately a third of nonoffending guardians respond with vacillation in support, and these nonoffending guardians are at greater risk for having their children removed. This article reconceptualizes vacillation in support as an ambivalent response. Drawing on the interdisciplinary literature, this article suggests that ambivalence in support reflects the confluence between the nonoffending guardian's valence toward the child and perpetrator. This article further proposes that ambivalence is normative when the costs of disclosure are high and when the nonoffending guardian is ambivalent/preoccupied in attachment. Ambivalence may also be both a precursor to and an effect of the traumatic experience of the disclosure on the nonoffending guardian. In a study of 30 nonoffending mothers whose partners sexually abused their children, these relationships were supported.

BACKGROUND: Osteochondritis dissecans (OCD) of the ankle is a disorder of the talar or distal tibial subchondral bone and articular cartilage whose incidence in children is not clearly known. PURPOSE: To assess the demographics and epidemiology of OCD of the ankle in children. STUDY DESIGN: Descriptive epidemiologic study. METHODS: A retrospective chart review of an integrated health system was conducted on patients with ankle OCD aged 2 to 19 years from 2007 to 2011, with >1 million patients in this cohort. Lesion location, laterality, and all patient demographics were recorded. Ankle OCD incidence was determined for the group as a whole and by both sex and age group (divided into age groups of 2-5, 6-11, and 12-19 years). The risk for ankle OCD for age group, sex, and ethnicity was assessed using multivariate logistic regression models. RESULTS: A total of 85 patients fit the inclusion criteria, and 71.8% of lesions found were in the medial talus, 56.5% of lesions were right sided, and none were bilateral. No ankle OCD lesions were found in 2- to 5-year-olds. The incidence of ankle OCD in patients aged 6 to 19 years was 4.6 per 100,000 overall and 3.2 and 6.0 per 100,000 for male and female patients, respectively. Patients aged 12 to 19 years represented the vast majority of those with OCD, with an incidence of 6.8 per 100,000 compared with 1.1 per 100,000 in those 6 to 11 years of age. In those aged 6 to 11 and 12 to 19 years, female patients had a respective incidence of 1.5 and 8.9 per 100,000, whereas male patients had a respective incidence of 0.7 and 4.8 per 100,000. The overall female/male ratio of ankle OCD was 1.6:1. Multivariate logistic regression analysis revealed a 6.9 times increased risk for ankle OCD in patients aged 12 to 19 years compared with those aged 6 to 11 years (95% CI, 3.8-12.5; P < .0001), and female patients had a 1.5 times greater risk for ankle OCD than male patients (95% CI, 1.0-2.3; P = .06). On the basis of race and ethnicity, non-Hispanic whites had the highest relative risk for disease and African Americans the lowest risk. CONCLUSION: In this population-based cohort study of pediatric ankle OCD, female patients had a greater incidence of OCD and a 1.5 times greater risk for ankle OCD compared with male patients. Teenagers had nearly 7 times the risk for ankle OCD compared with children 6 to 11 years of age.

BACKGROUND: Although many etiological theories have been proposed for osteochondritis dissecans (OCD), its etiology remains unclear. Histological analysis of the articular cartilage and subchondral bone tissues of OCD lesions can provide useful information about the cellular changes and progression of OCD. Previous research is predominantly comprised of retrospective clinical studies from which limited conclusions can be drawn. QUESTIONS/PURPOSES: The purposes of this study were threefold: (1) Is osteonecrosis a consistent finding in OCD biopsy specimens? (2) Is normal articular cartilage a consistent finding in OCD biopsy specimens? (3) Do histological studies propose an etiology for OCD based on the tissue findings? METHODS: We searched the PubMed, Embase, and CINAHL databases for studies that conducted histological analyses of OCD lesions of the knee and identified 1560 articles. Of these, 11 met our inclusion criteria: a study of OCD lesions about the knee, published in the English language, and performed a histological analysis of subchondral bone and articular cartilage. These 11 studies were assessed for an etiology proposed in the study based on the study findings. RESULTS: Seven of 11 studies reported subchondral bone necrosis. Four studies reported normal articular cartilage, two studies reported degenerated or irregular articular cartilage, and five studies found a combination of normal and degenerated or irregular articular cartilage. Five studies proposed trauma or repetitive stress and two studies proposed poor blood supply as possible etiologies. CONCLUSIONS: We found limited research on histological analysis of OCD lesions of the knee. Future studies with consistent methodology are necessary to draw major conclusions about the histology and progression of OCD lesions. Inconsistent histologic findings have resulted in a lack of consensus regarding the presence of osteonecrosis, whether the necrosis is primary or secondary, the association of cartilage degeneration, and the etiology of OCD. Such studies could use a standardized grading system to allow better comparison of findings.

SATB2-associated syndrome (SAS) is an autosomal dominant disorder characterized by significant neurodevelopmental disabilities with limited to absent speech, behavioral issues, and craniofacial anomalies. Previous studies have largely been restricted to case reports and small series without in-depth phenotypic characterization or genotype-phenotype correlations. Seventy two study participants were identified as part of the SAS clinical registry. Individuals with a molecularly confirmed diagnosis of SAS were referred after clinical diagnostic testing. In this series we present the most comprehensive phenotypic and genotypic characterization of SAS to date, including prevalence of each clinical feature, neurodevelopmental milestones, and when available, patient management. We confirm that the most distinctive features are neurodevelopmental delay with invariably severely limited speech, abnormalities of the palate (cleft or high-arched), dental anomalies (crowding, macrodontia, abnormal shape), and behavioral issues with or without bone or brain anomalies. This comprehensive clinical characterization will help clinicians with the diagnosis, counseling and management of SAS and help provide families with anticipatory guidance.

PURPOSE: TANGO2-related disorders were first described in 2016 and prior to this publication, only 15 individuals with TANGO2-related disorder were described in the literature. Primary features include metabolic crisis with rhabdomyolysis, encephalopathy, intellectual disability, seizures, and cardiac arrhythmias. We assess whether genotype and phenotype of TANGO2-related disorder has expanded since the initial discovery and determine the efficacy of exome sequencing (ES) as a diagnostic tool for detecting variants. METHODS: We present a series of 14 individuals from 11 unrelated families with complex medical and developmental histories, in whom ES or microarray identified compound heterozygous or homozygous variants in TANGO2. RESULTS: The initial presentation of patients with TANGO2-related disorders can be variable, including primarily neurological presentations. We expand the phenotype and genotype for TANGO2, highlighting the variability of the disorder. CONCLUSION: TANGO2-related disorders can have a more diverse clinical presentation than previously anticipated. We illustrate the utility of routine ES data reanalysis whereby discovery of novel disease genes can lead to a diagnosis in previously unsolved cases and the need for additional copy-number variation analysis when ES is performed.

Normal development of the genitourinary (GU) tract is a complex process that frequently goes awry. In male children the most frequent congenital GU anomalies are cryptorchidism (1-4%), hypospadias (1%) and micropenis (0.35%). Bladder exstrophy and epispadias complex (BEEC) (1∶47000) occurs less frequently but significantly impacts patients' lives. Array comparative genomic hybridization (aCGH) identified seven individuals with overlapping deletions in the 2p15 region (66.0 kb-5.6 Mb). Six of these patients have GU defects, while the remaining patient has no GU defect. These deletions encompass the transcription factor OTX1. Subjects 2-7 had large de novo CNVs (2.39-6.31 Mb) and exhibited features similar to those associated with the 2p15p16.1 and 2p15p14 microdeletion syndromes, including developmental delay, short stature, and variable GU defects. Subject-1 with BEEC had the smallest deletion (66 kb), which deleted only one copy of OTX1. Otx1-null mice have seizures, prepubescent transient growth retardation and gonadal defects. Two subjects have short stature, two have seizures, and six have GU defects, mainly affecting the external genitalia. The presence of GU defects in six patients in our cohort and eight of thirteen patients reported with deletions within 2p14p16.1 (two with deletion of OTX1) suggest that genes in 2p15 are important for GU development. Genitalia defects in these patients could result from the effect of OTX1 on pituitary hormone secretion or on the regulation of SHH signaling, which is crucial for development of the bladder and genitalia.

BACKGROUND: Exon-targeted microarrays can detect small (<1000 bp) intragenic copy number variants (CNVs), including those that affect only a single exon. This genome-wide high-sensitivity approach increases the molecular diagnosis for conditions with known disease-associated genes, enables better genotype-phenotype correlations, and facilitates variant allele detection allowing novel disease gene discovery. METHODS: We retrospectively analyzed data from 63,127 patients referred for clinical chromosomal microarray analysis (CMA) at Baylor Genetics laboratories, including 46,755 individuals tested using exon-targeted arrays, from 2007 to 2017. Small CNVs harboring a single gene or two to five non-disease-associated genes were identified; the genes involved were evaluated for a potential disease association. RESULTS: In this clinical population, among rare CNVs involving any single gene reported in 7200 patients (11%), we identified 145 de novo autosomal CNVs (117 losses and 28 intragenic gains), 257 X-linked deletion CNVs in males, and 1049 inherited autosomal CNVs (878 losses and 171 intragenic gains); 111 known disease genes were potentially disrupted by de novo autosomal or X-linked (in males) single-gene CNVs. Ninety-one genes, either recently proposed as candidate disease genes or not yet associated with diseases, were disrupted by 147 single-gene CNVs, including 37 de novo deletions and ten de novo intragenic duplications on autosomes and 100 X-linked CNVs in males. Clinical features in individuals with de novo or X-linked CNVs encompassing at most five genes (224 bp to 1.6 Mb in size) were compared to those in individuals with larger-sized deletions (up to 5 Mb in size) in the internal CMA database or loss-of-function single nucleotide variants (SNVs) detected by clinical or research whole-exome sequencing (WES). This enabled the identification of recently published genes (BPTF, NONO, PSMD12, TANGO2, and TRIP12), novel candidate disease genes (ARGLU1 and STK3), and further confirmation of disease association for two recently proposed disease genes (MEIS2 and PTCHD1). Notably, exon-targeted CMA detected several pathogenic single-exon CNVs missed by clinical WES analyses. CONCLUSIONS: Together, these data document the efficacy of exon-targeted CMA for detection of genic and exonic CNVs, complementing and extending WES in clinical diagnostics, and the potential for discovery of novel disease genes by genome-wide assay.

BACKGROUND: Mycobacterium abscessus is an uncommon cause of invasive odontogenic infection. METHODS: M abscessus-associated odontogenic infections occurred in a group of children after they each underwent a pulpotomy. A probable case-child was defined as a child with facial or neck swelling and biopsy-confirmed granulomatous inflammation after a pulpotomy between October 1, 2013, and September 30, 2015. M abscessus was isolated by culture in confirmed case-children. Clinical presentation, management, and outcomes were determined by medical record abstraction. RESULTS: Among 24 children, 14 (58%) were confirmed case-children. Their median age was 7.3 years (interquartile range, 5.8-8.2 years), and the median time from pulpotomy to symptom onset was 74 days (range, 14-262 days). Clinical diagnoses included cervical lymphadenitis (24 [100%] of 24), mandibular or maxillary osteomyelitis (11 [48%] of 23), and pulmonary nodules (7 [37%] of 19). Each child had ≥1 hospitalization and a median of 2 surgeries (range, 1-6). Of the 24 children, 12 (50%) had surgery alone and 11 (46%) received intravenous (IV) antibiotics. Nineteen of the 24 (79%) children experienced complications, including vascular access malfunction (7 [64%] of 11), high-frequency hearing loss (5 [56%] of 9), permanent tooth loss (11 [48%] of 23), facial nerve palsy (7 [29%] of 24), urticarial rash (3 [25%] of 12), elevated liver enzyme levels (1 [20%] of 5), acute kidney injury (2 [18%] of 11), incision dehiscence/fibrosis (3 [13%] of 24), and neutropenia (1 [9%] of 11). CONCLUSIONS: M abscessus infection was associated with significant medical morbidity and treatment complications. Unique manifestations included extranodal mandibular or maxillary osteomyelitis and pulmonary nodules. Challenges in the identification of case-children resulted from an extended incubation period and various clinical manifestations. Clinicians should consider the association between M abscessus infection and pulpotomy in children who present with subacute cervical lymphadenitis. The use of treated/sterile water during pulpotomy might prevent further outbreaks.

BACKGROUND: Canada's publicly funded blood system has recently introduced high-purity concentrates as the standard treatment for individuals with hemophilia. The added cost and the need to document patient outcomes have prompted the consideration of a national blood product monitoring system. STUDY DESIGN AND METHODS: This study investigates the suitability of the Canadian Hemophilia Registry (CHR) as the basis of such a monitoring system by assessing the degree to which it represents users of factor concentrates. RESULTS: Currently, there are 1978 individuals registered with the CHR, of whom 1594 (81%) have hemophilia A and 384 (19%) have hemophilia B. The total prevalence is 7.2 per 10(5) population, with the prevalence of severe cases being 2.3 per 10(5). This overall prevalence is similar to that seen in other countries with national registries. The CHR national prevalence also compares favorably with that in the province of Quebec, where registration of users of blood products is compulsory. The CHR figures indicate that the number of persons currently infected with human immunodeficiency virus, both alive and dead, is 652, which is similar to the number of applicants (658) to the federal government's assistance program. The registry is stable, and the number of persons with severe cases, other than young children, newly registered or lost to follow-up during the last 2 years is very small. CONCLUSION: The CHR includes the vast majority of factor concentrate users and is therefore ideal as the basis for a national monitoring system.

Although initially considered rare, anterior cruciate ligament (ACL) ruptures in pediatric patients recently have increased substantially as a result of greater awareness of the injury and increased participation in youth sports. Although pediatric patients with an ACL injury and a clinically stable joint may handle the injury well and return to sports activity without requiring surgical reconstruction, young, active patients with an ACL rupture and an unstable joint may be good candidates for ACL reconstruction to prevent ongoing instability and additional joint damage. ACL reconstruction techniques have been developed to prevent physeal injury in skeletally immature patients. The surgical treatment of skeletally immature patients with an ACL rupture may differ from that of adults with an ACL rupture and presents unique challenges with regard to reconstruction technique selection, graft preparation, rehabilitation, and return to sports activity. Orthopaedic surgeons should understand various physeal-sparing ACL reconstruction techniques and the general challenges associated with the surgical management of ACL ruptures in pediatric patients.

BACKGROUND: Osteochondritis dissecans (OCD) is a joint disorder of the subchondral bone and articular cartilage whose association with obesity in children is not clearly known. The purpose of this study was to assess the magnitude of the association between childhood obesity and the occurrence of OCD of the knee, ankle, and elbow in children. METHODS: A retrospective chart review of an integrated health system was performed on OCD patients aged 2 to 19 from 2007 to 2011, with over 1 million patients in this cohort. Lesion location, laterality, and all patient demographics were recorded. The body mass index (BMI) for each patient in the cohort was used to stratify patients into 5 weight classes (underweight, normal weight, overweight, moderately obese, and extremely obese) based on BMI-for-age. The associations between the 5 weight classes and OCD of the ankle, knee, and elbow were assessed using multiple logistic regression models to estimate odds ratios (OR) and 95% confidence intervals using multivariate analysis to adjust for patient demographic variables. RESULTS: In total, 269 patients fit the inclusion criteria. Mean BMI, both absolute and percentile, was significantly higher for patients with OCD of the knee, elbow, and ankle than patients without OCD. In the multivariate analysis, extremely obese patients were found to have an increased OR of OCD for all patients, with an 86% increased risk of any OCD compared with normal weight patients. In addition, assessment by different types of OCD revealed that extremely obese patients had an increased OR of OCD of the elbow and ankle individually, with a 3.1 times increased OCD elbow risk and 3.0 times increased risk of ankle OCD in extremely obese patients. Although extremely obese patients did not have a statistically significant increased risk of knee OCD, moderately obese patients did have a 1.8 times increased risk of knee OCD as compared with normal weight children. There were no significantly different risks of any type of OCD seen in overweight or underweight patients as compared with normal weight patients. CONCLUSIONS: In this population-based cohort study, extreme obesity is strongly associated with an increased risk of OCD overall and OCD of the elbow and ankle specifically. In addition, moderate obesity is associated with an increased risk of knee OCD. All types of OCD were also found to have a significantly greater average BMI when compared with patients without OCD. LEVEL OF EVIDENCE: Level IV-descriptive epidemiology study.

BACKGROUND: The anterolateral ligament (ALL) of the knee has been identified as a structure that limits internal rotation, and thus, affects the pivot shift mechanism. It has previously been reported in a high percentage of adult subjects. The purpose of the current study was to evaluate whether the ALL could be identified on pediatric cadaveric knee specimens and compare these findings to previously published reports. METHODS: Eight skeletally immature cadaver knee specimens were examined through gross dissection: ages 3 months, 4 months, 1 year, 2 years, 3 years, 3 years, 8 years, and 10 years. There were 3 male and 5 female (7 right, 1 left) specimens. The presence or absence of the ALL was documented in each specimen, through dissection, intermittent internal and external rotation of the tibia, and anterior translation of the tibia, to produce tension of the lateral collateral tissues and joint capsule. These dissections were performed by a group of fellowship-trained orthopaedic surgeons. RESULTS: The iliotibial band, entire lateral joint capsule, lateral collateral ligament, and popliteus were readily identified in each specimen. In 7 specimens, a distinct ALL structure was not identified during dissection. The ALL was identified in 1 of 8 specimens (1-year-old female, right knee). The ALL was further delineated under applied internal rotational stress. CONCLUSIONS: Previous research has suggested that this ligament is present in the majority of adult specimens. This finding was not reproduced in the current study of pediatric cadaveric specimens, where only one of 8 specimens had an identifiable ALL. This suggests that this ligament may develop later in life, after physiological loads are applied to the joint capsule. Further research in both adult and pediatric knees needs to be conducted to further elucidate the development of this ligament, and the role of this structure in knee stability. CLINICAL RELEVANCE: The ALL is a knee ligament that has been described in adults. However, it is unclear whether this structure is present or fully developed in younger populations. The current study sought to identify the ALL in pediatric cadaver knee specimens, identifying this structure in only one of 8 specimens. The findings of this study suggest that the ALL may be an inconsistent structure in the pediatric population.

BACKGROUND: Although meningitis is rare in previously healthy term infants, lumbar puncture is often performed to evaluate for source of illness. This study was performed to determine the time to detection for positive cerebrospinal fluid (CSF) cultures and to provide an update on the current epidemiology of bacterial meningitis in term infants. METHODS: This study was a multicenter, retrospective review of positive CSF cultures in infants ≤90 days of age. Specimens were drawn in the emergency department or inpatient setting between January 2000 and December 2013. Cultures were deemed true pathogens or contaminant species based on the attending physician’s treatment plan. Cultures from premature infants, an operative source, or those with significant medical history were excluded. RESULTS: A total of 410 positive CSF culture results were included, with 53 (12.9%) true pathogens and 357 (87.1%) contaminant species. The mean ± SD time to detection for true pathogens was 28.6 ± 16.8 hours (95% confidence interval, 24–33.2); for contaminant species, it was 68.1 ± 36.2 hours (95% confidence interval, 64.3–71.9). Forty-three true-positive cases (81.1%) were positive in ≤36 hours. The most common pathogen was group B Streptococcus (51%), followed by Escherichia coli (13%) and Streptococcus pneumoniae (9%). CONCLUSIONS: The majority of pathogenic bacteria in CSF exhibit growth within 36 hours. Most growth from CSF cultures in febrile infants is treated as contamination. The epidemiology of meningitis has remained constant, with group B Streptococcus as the predominant pathogen, despite changes noted in the epidemiology of bacteremia in this population.

BACKGROUND: Osteochondritis dissecans (OCD) has frequently been described in children and adolescents, but cases of OCD in adults are certainly encountered. Little has been published on the epidemiology of OCD in adult patients. PURPOSE: To assess the frequency of OCD lesions in adults and assess the risk by age, sex, and ethnicity. STUDY DESIGN: Descriptive epidemiology study. METHODS: The authors assessed all patients aged 20 to 45 years from the entire database of patients enrolled as members of Kaiser Permanente Southern California from January 2011 until December 2013. Kaiser Southern California is an integrated health care system serving a racially, ethnically, and socioeconomically diverse population of >3.5 million patients. A retrospective chart review was done on OCD during this period. Inclusion criteria included OCD of any joint. Exclusion criteria included traumatic osteochondral fractures and coexistence of intra-articular lesions other than OCD. Joint involvement/location, laterality, and all patient demographics were recorded. RESULTS: Among 122 patients, a total of 124 OCD lesions were found. The majority of lesions were in the ankle (n = 76) and knee (n = 43), with 3 foot lesions and 2 elbow lesions identified. OCD lesions were identified in 75 men (62%) and 47 women (38%). Overall incidence rates per 100,000 person-years were 3.42 for all OCD, 2.08 for ankle OCD, and 1.21 for knee OCD. The relative risk of adult OCD for men was twice that of women. The relative risk of adult OCD for white patients was 2.3 that of Asians and 1.7 that of Hispanics. Risk of knee OCD was 3.6 times higher for men than women. As compared with women, men had a higher risk for lateral femoral condyle OCD lesions versus the medial femoral condyle ( P = .05; odds ratio [OR], 5.19). CONCLUSION: This large cohort study of Southern California adults with OCD demonstrated an increased OR for men (vs women) of OCD in all joints. The majority of symptomatic lesions were present in the ankle rather than the knee, as previously found in children. White and black patients had the highest OR of OCD; men had a significantly greater OR of lateral femoral condyle knee lesions as compared with women.

BACKGROUND: Patellar dislocations are common in skeletally immature athletes, and the medial patellofemoral ligament (MPFL) is an important primary restraint to lateral patellar translation. The relationship between the MPFL femoral origin footprint and femoral physis is unclear. The purpose of this study was to evaluate the MPFL femoral origin footprint and its relationship to the femoral physis in skeletally immature anatomic specimens. METHODS: Six skeletally immature cadaver knee specimens were examined through gross dissection (group A: 1, 11, and 11 mo; and group B: 8, 10, and 11 y). Metallic markers were placed at the center of the MPFL femoral origin footprint. Computed tomography scans for each specimen were analyzed. The MPFL footprint width, and the vertical distances from the center and proximal extent of the MPFL footprint to the medial aspect of the physis were measured. RESULTS: The mean width of the MPFL femoral origin footprint was 0.70 cm (0.48 to 1.09 cm) and 1.12 cm (1.03 to 1.29 cm) for groups A and B, respectively. The mean distance from the center of the MPFL origin footprint to medial aspect of the distal femoral physis was 0.90 cm (0.52 to 1.30 cm) and 0.40 cm (0.00 to 0.86 cm) distal to the physis for groups A and B, respectively. The mean distance from the proximal extent of the MPFL origin footprint to the medial aspect of the femoral physis was -0.55 cm (-0.28 to -1.03 cm) and 0.16 cm (-0.34 to 0.64 cm) for groups A and B, respectively. CONCLUSIONS: All subjects were found to have a center of the MPFL origin footprint at or below the physis. The proximal extent of the MPFL origin footprint was found to extend above the physis in the 2 older specimens. CLINICAL RELEVANCE: The relationship of the MPFL origin footprint to the femoral physis in the skeletally immature is not well understood. These dissections may be useful to surgeons performing MPFL reconstructions in skeletally immature patients.

The purpose of this article is to present a study of intervening variables for guardian support. It is this article's thesis that guardian support is better conceptualized as a complex reaction to the disclosure of abuse that is shaped by a number of factors, some of the most important of which are the stressors impinging on guardians and their previous patterns of relating within the family. The sample included 92 guardians of sexually abused children presenting at a medical center for a sexual abuse medical and forensic evaluation. This study found that the most important intervening variables for guardian support in multivariate analysis were the attachment/relationship style of child and guardian and whether a second guardian accompanied the child to the hospital. This study highlights the importance of relational considerations between the child and nonoffending guardian as well as the importance of using more than a single nonoffending caregiver.

Abstract Objective FOXG 1 syndrome is a rare neurodevelopmental disorder associated with heterozygous FOXG 1 variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations. Methods We compiled 34 patients with a heterozygous (likely) pathogenic FOXG 1 variant. Qualitative assessment of cerebral anomalies was performed by standardized re‐analysis of all 34 MRI data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult Foxg1 +/− mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies. Results Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in FOXG 1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of Foxg1 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix. Interpretation Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG 1 syndrome.