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BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare, degenerative, recessive X-linked neuromuscular disease. Mutations in the gene encoding dystrophin lead to the absence of functional dystrophin protein. Individuals living with DMD exhibit progressive muscle weakness resulting in loss of ambulation and limb function, respiratory insufficiency, and cardiomyopathy, with multiorgan involvement. Adeno-associated virus vector-mediated gene therapy designed to enable production of functional dystrophin protein is a new therapeutic strategy. Delandistrogene moxeparvovec (Sarepta Therapeutics, Cambridge, MA) is indicated for treatment of ambulatory pediatric patients aged 4 through 5 years with DMD who have an indicated mutation in the DMDgene.OBJECTIVE: Evidence-based considerations for management of potential adverse events following gene therapy treatment for DMD are lacking in clinical literature. Our goal was to provide interdisciplinary consensus considerations for selected treatment-related adverse events (TRAEs) (vomiting, acute liver injury, myocarditis, and immune-mediated myositis) that may arise following gene therapy dosing with delandistrogene moxeparvovec.METHODS: An interdisciplinary panel of 12 specialists utilized a modified Delphi process to develop consensus considerations for the evaluation and management of TRAEs reported in delandistrogene moxeparvovec clinical studies. Panelists completed 2 Questionnaires prior to gathering for an in-person discussion. Consensus was defined as a majority (=58% ; 7/12) of panelists either agreeing or disagreeing.RESULTS: Panelists agreed that the choice of baseline assessments should be informed by individual clinical indications, the treating provider’s judgment, and prescribing information. Corticosteroid dosing for treatment of TRAEs should be optimized by considering individual risk versus benefit for each indication. In all cases involving patients with a confirmed TRAE, consultations with appropriate specialists were suggested.CONCLUSIONS: The Delphi Panel established consensus considerations for the evaluation and management of potential TRAEs for patients receiving delandistrogene moxeparvovec, including vomiting, acute liver injury, myocarditis, and immune-mediated myositis.

Objective: This report summarizes the key discussions from the “Early Care (0–3 years) in Duchenne Muscular Dystrophy” meeting, which aimed to address the challenges and opportunities in the diagnosis and care of Duchenne muscular dystrophy (DMD) and female carriers within the 0–3-year age group.Methods: The meeting brought together experts and healthcare providers who shared insights, discussed advancements in DMD care, and identified research needs. Presentations covered diagnostic challenges, approved therapies, clinical trials, identification of young female carriers, and the importance of clinical care and support for families.Results: The meeting highlighted the importance of timely diagnosis and the lack of evidence-based guidelines for the care of children with DMD aged 0–3 years. Diagnostic challenges were discussed, including delays in receiving a DMD diagnosis and disparities based on ethnicity. The potential benefits and process of newborn screening were addressed. Approved therapeutic interventions, such as corticosteroids and exon-skipping drugs, were explored, with studies indicating the potential benefits of early initiation of corticosteroid therapy and the safety of exon-skipping drugs in DMD. Clinical trials involving infants and young boys were discussed, focusing on drugs like ataluren, vamorolone, and gene therapies. The meeting emphasized the importance of clinical care and support for families, including comprehensive information provision, early intervention services, and individualized support. The identification and care of young female carriers were also addressed.Conclusion: The meeting provided a platform for experts and healthcare providers to discuss and identify key aspects of early care for children with DMD aged 0–3 years. The meeting emphasized the need for early diagnosis, evidence-based guidelines, and comprehensive care and support for affected children and their families. Further research, collaboration, and the development of consensus guidelines are needed to improve early diagnosis, treatment, and outcomes in this population.

The diagnosis of Duchenne and Becker muscular dystrophy (DBMD) is made by genetic testing in approximately 95% of cases. Although specific mutations can be associated with skeletal muscle phenotype, pulmonary and cardiac comorbidities (leading causes of death in Duchenne) have not been associated with Duchenne muscular dystrophy mutation type or location and vary within families. Therefore, identifying predictors for phenotype severity beyond frameshift prediction is important clinically. We performed a systematic review assessing research related to genotype–phenotype correlations in DBMD. While there are severity differences across the spectrum and within mild and severe forms of DBMD, few protective or exacerbating mutations within the dystrophin gene were reported. Except for intellectual disability, clinical test results reporting genotypic information are insufficient for clinical prediction of severity and comorbidities and the predictive validity is too low to be useful when advising families. Including expanded information coupled with proposed severity predictions in clinical genetic reports for DBMD is critical for improving anticipatory guidance.

Background: Edasalonexent (CAT-1004) is an orally-administered novel small molecule drug designed to inhibit NF-?B and potentially reduce inflammation and fibrosis to improve muscle function and thereby slow disease progression and muscle decline in Duchenne muscular dystrophy (DMD).Objective: This international, randomized 2?:?1, placebo-controlled, phase 3 study in patients =4?–?

Background: Expert guidelines recommend annual monitoring of 25-hydroxyvitamin D (25-OHD) and maintaining 25-OHD =30?ng/ml in patients with dystrophinopathies.Objective: We hypothesized that 25-OHD remains stable and requires less frequent monitoring in patients taking stable maintenance doses of vitamin D.Methods: We performed a retrospective cohort study, using the electronic health record to identify 26 patients with dystrophinopathies with a baseline 25-OHD =30?ng/mL and at least one additional 25-OHD measurement. These patients had received a stable dose of vitamin D for =3 months prior to their baseline 25-OHD measurement and throughout follow-up. The main outcome measured was the mean duration time the subjects spent with a 25-OHD =30 ng/mL.Results: Only 19% of patients dropped their 25-OHD to

The gene (Huntingtin or HTT) causing Huntington’s disease (HD) is vital for development and is expressed throughout the brain and body lifelong. The mutant form (mHTT) may influence growth and development. To determine the impact of mHTTon human measures of growth, including height, weight, and body mass index (BMI), between child and adolescent carriers of mHTTand control peers. Children ages 6–18 years of age (n = 186) at risk for HD were enrolled in the KidsHD study. For research purposes only, genetic testing was performed to classify participants as Gene-Expanded (GE = 78) or as Gene Non-Expanded (GNE = 108). Outcome measures included height, weight, and body mass index (BMI). Mixed models were used to determine if non-linear age trends differed between groups for BMI, height, and weight. Differences were seen in the trajectory of BMI in which the GE group reached a plateau in late adolescence with no further increase, compared with a nearly linear increase in the GNE group. There was a significant sex interaction pattern where GE males were taller than GNE males in adolescence, in the presence of similar weight. In contrast, GE females weighed significantly less than their GNE counterparts in adolescence, in the presence of similar height. Measures of growth are abnormal in child and adolescent carriers of mHTT, decades before HD onset. Although further studies are needed for replication, the current findings suggest that developmental aberrations may be systemic and a vital part of disease pathology.

Aim:Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). Materials & methods:Data from the two completed randomized controlled trials (ClinicalTrials.gov: NCT00592553; NCT01826487) of ataluren in nmDMD were combined to examine the intent-to-treat (ITT) populations and two patient subgroups (baseline 6-min walk distance [6MWD] ≥300–<400 or <400 m). Meta-analyses examined 6MWD change from baseline to week 48. Results:Statistically significant differences in 6MWD change with ataluren versus placebo were observed across all three meta-analyses. Least-squares mean difference (95% CI): ITT (n = 342), +17.2 (0.2–34.1) m, p = 0.0473; ≥300–<400 m (n = 143), +43.9 (18.2–69.6) m, p = 0.0008; <400 m (n = 216), +27.7 (6.4–49.0) m, p = 0.0109. Conclusion:These meta-analyses support previous evidence for ataluren in slowing disease progression versus placebo in patients with nmDMD over 48 weeks. Treatment benefit was most evident in patients with a baseline 6MWD ≥300–<400 m (the ambulatory transition phase), thereby informing future trial design.

Congenital muscular dystrophy type 1A (MDC1A) is caused by recessive variants in laminin α2(LAMA2). Patients have been found to have white matter signal abnormalities on magnetic resonance imaging (MRI) but rarely structural brain abnormalities. We describe the autopsy neuropathology in a 17-year-old with white matter signal abnormalities on brain MRI. Dystrophic pathology was observed in skeletal muscle, and the sural nerve manifested a mild degree of segmental demyelination and remyelination. A diffuse, bilateral cobblestone appearance, and numerous points of fusion between adjacent gyri were apparent on gross examination of the cerebrum. Brain histopathology included focal disruptions of the glia limitans associated with abnormal cerebral cortical lamination or arrested cerebellar granule cell migration. Subcortical nodular heterotopia was present within the cerebellar hemispheres. Sampling of the centrum semiovale revealed no light microscopic evidence of leukoencephalopathy. Three additional MDC1A patients were diagnosed with cobblestone malformation on brain MRI. Unlike the autopsied patient whose brain had a symmetric distribution of cobblestone pathology, the latter patients had asymmetric involvement, most severe in the occipital lobes. These cases demonstrate that cobblestone malformation may be an important manifestation of the brain pathology in MDC1A and can be present even when patients have a structurally normal brain MRI.

Purpose Food insecurity has far-reaching consequences for health and well-being, especially during pregnancy and postpartum periods. This study examines a food-is-medicine approach that aimed to reduce food insecurity, maternal stress, depression, anxiety, preterm labor, and low birthweight.Design Pre-post interventional study of FreshRx: Nourishing Healthy Starts, a pregnancy focused food-is-medicine program led by a local hunger relief organization and obstetrics department.Setting St. Louis, Missouri, a Midwestern U.S. city with higher-than-average infant mortality, low birthweight, and preterm birth rates.Sample Participants (N = 125) recruited from a local obstetrics clinic had pregnancies earlier than 24 weeks gestation; spoke English; and were enrolled in Medicaid. At baseline, 67.0% reported very low food security and none reported high food security, while 34.7% indicated depressive symptoms.Intervention FreshRx included weekly deliveries of fresh food meal kits, nutrition counseling and education, care coordination, and supportive services.Measures 18-Question U.S. Household Food Security Survey, Edinburgh Postnatal Depression Scale, birthweight, gestational age.Analysis Single arm pre-post analysis.Results Average gestational age of 38.2 weeks (n = 84) and birthweight of 6.7 pounds (n = 81) were higher than rates for the general population in the area. For study participants who completed a sixty-day post-partum assessment, 13% (n = 45) indicated maternal depression (P< .01).Conclusion Food-is-medicine interventions may be an efficient, effective, and equitable tool for improving birth and maternal health outcomes.

Background:Smoking during pregnancy has detrimental effects on mother and fetus. Text messaging has been utilized to improve patient care. Objective:To evaluate the impact of text messaging on smoking cessation rates among pregnant women in addition to standard of care (SOC) smoking cessation services. Our SOC includes pharmacist-driven education with or without nicotine patch or bupropion. Methods:This randomized, open-label, prospective trial was conducted at a maternal fetal care center from May 2014 to January 2016. Pregnant patients in the preparation stage of change were randomized to text messaging or SOC. The primary outcome was smoking cessation verified with exhaled carbon monoxide levels (eCO) 2 weeks from quit date. All received clinical pharmacist weekly calls for 3 weeks and biweekly visits until pharmacotherapy completion. The text messaging group also received predetermined motivational messages. Results:Of 49 randomized patients, 13 withdrew, and 6 were lost to follow-up. The remaining included 14 texting and 16 SOC patients. eCO-verified cessation was achieved by 57.1% in the texting group versus 31.3% in the control (P= 0.153). Overall, 64.3% of the texting group achieved an eCO below 8 ppm at ≥1 visit versus 37.5% in the control group (P= 0.143). No difference was found in birth outcomes. The study was underpowered because of slow enrollment and high drop-out rates. Conclusions and Relevance:Text messaging had minimal impact on improving smoking cessation rates in the obstetric population. However, further research is warranted because of the underpowered nature of this trial. Given the detrimental effects of smoking in pregnancy, more comprehensive cessation strategies are warranted.

A Congenital Muscular Dystrophy (CMD) Working Group (WG) consisting of international experts reviewed common data elements (CDEs) previously developed for other neuromuscular diseases (NMDs) and made recommendations for all types of studies on CMD. To develop a comprehensive set of CDEs, data definitions, case report forms and guidelines for use in CMD clinical research to facilitate interoperability of data collection, as part of the CDE project at the National Institute of Neurological Disorders and Stroke (NINDS). One working group composed of ten experts reviewed existing NINDS CDEs and outcome measures, evaluated the need for new elements, and provided recommendations for CMD clinical research. The recommendations were compiled, internally reviewed by the CMD working group, and posted online for external public comment. The CMD working group and the NIH CDE team reviewed the final version before release. The NINDS CMD CDEs and supporting documents are publicly available on the NINDS CDE website (https://www.commondataelements.ninds.nih.gov/CMD.aspx#tab=Data_Standards). Content areas include demographics, social status, health history, physical examination, diagnostic tests, and guidelines for a variety of specific outcomes and endpoints. The CMD CDE WG selected these documents from existing versions that were generated by other disease area working groups. Some documents were tailored to maximize their suitability for the CMD field. Widespread use of CDEs can facilitate CMD clinical research and trial design, data sharing and retrospective analyses. The CDEs that are most relevant to CMD research are like those generated for other NMDs, and CDE documents tailored to CMD are now available to the public. The existence of a single source for these documents facilitates their use in research studies and offers a clear mechanism for the discussion and update of the information as knowledge is gained.

Duchenne muscular dystrophy (DMD) is a severe, progressive, and rare neuromuscular, X-linked recessive disease. Dystrophin deficiency is the underlying cause of disease; therefore, mutation-specific therapies aimed at restoring dystrophin protein production are being explored. We aimed to assess the efficacy and safety of ataluren in ambulatory boys with nonsense mutation DMD.

Background:Asthma complicates 4% to 8% of pregnancies. The impact of clinical pharmacists providing asthma management and education to obstetric patients is unknown. Objective:Evaluate the impact of and patient satisfaction with clinical pharmacy services on asthma in pregnancy. Methods:This prospective quasi-experimental study enrolled 30 pregnant patients with asthma and assessed perceived asthma understanding, control, and inhaler technique before and after a clinical pharmacist visit and education. The primary outcome was change in pre- and postsurvey scores. Items were rated on a 5-point Likert-type scale; higher scores represented higher perceived knowledge or satisfaction. Secondary outcomes included inhaler technique scores, asthma control, correlating patient-specific factors with the primary outcome, and level of patient satisfaction with clinical pharmacy services. Results:Perceived knowledge of asthma in pregnancy median score (maximum score 50) significantly increased with clinical pharmacy education (37.5 pre vs 49 post, P= .001). Prior to clinical pharmacy services, patients highly rated their perceived knowledge of asthma in pregnancy with median scores on 7 of 10 items between 4 and 5. Despite this, significant changes were observed on 9 items. The proportion of patients with controlled asthma significantly increased after the pharmacist visit (33.3% vs 90%, P< .001). Satisfaction with clinical pharmacy services was overwhelmingly positive with average scores on all items 4.5 to 5. Inhaler technique scores significantly increased from baseline to follow-up (4 vs 7, P= .001). Conclusions:Pharmacists significantly improved patient perceived knowledge about asthma, asthma control, and inhaler technique. Patients were overwhelmingly satisfied with the care provided by the pharmacist.

Objective:To evaluate physician satisfaction with clinical pharmacy services in an obstetrics teaching clinic. Study Design:A 35-question survey was created to evaluate demographics and provider satisfaction with clinical pharmacy services using 5-point Likert scale and open response questions. Surveys were administered to all clinic attendings, maternal fetal medicine fellows, and OB/Gyn residents in June 2014 via Survey Monkey. Results:Thirty-one physicians (83.8%) completed the survey. The first set of questions utilized a 5-point Likert-type scale ranging from “poor” (1) to “excellent” (5) and evaluated respondents’ impressions of the clinical pharmacists’ clinical knowledge and professional behavior. The median score was 5 (“excellent”) on all items in the survey, and many demonstrated an average response of 4.81 to 4.9 or higher, demonstrating that almost all respondents chose “excellent.” The next set of questions assessed the clinical pharmacist’s role with the clinic’s multidisciplinary team and asked respondents to answer questions based on a 5-point Likert-type scale ranging from “strongly disagree” (1) to “strongly agree” (5). The majority of responses to questions in this section were between 4.19 and 4.84. Reasons for referring patients to the clinical pharmacist were smoking cessation, asthma management, psych medication use/issues, adherence/polypharmacy, medication reconciliation, counseling on medication safety in pregnancy, insulin/heparin administration, and substance abuse. Conclusions:Overall, the survey identified a positive response and high level of physician satisfaction with clinical pharmacy services. Clinical pharmacy has the capacity to enhance pregnancy care and should be more routinely integrated into the prenatal care team.

Background:Facioscapulohumeral dystrophy is the third most common muscular dystrophy and the one most likely to present primarily in the head and neck.Methods:In this report, we present a case of a young child with subtle progressive bilateral facial weakness whose workup ultimately led to this diagnosis. Paralysis in this disorder is secondary to worsening muscle atrophy, which typically progresses in a cephalad to caudad direction. Despite facial paralysis being a key and early component of this illness, no prior descriptions in the otolaryngology literature exist.Discussion:The case described is unusual in that the patient initially presented to a community otolaryngologist. In addition to workup, the disease characteristics, head and neck manifestations, and prognosis are discussed.

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.

To describe the hearing loss in facioscapulohumeral muscular dystrophy (FSHD) and examine the relationship to genotype.

Mutations in the X-linked gene encoding dystrophin cause skeletal and cardiac muscle diseases in men. Female “carriers” also can develop overt disease. The purpose of this study was to ascertain the prevalence of cardiac contractile abnormalities in dystrophinopathy carriers.

Parsimony-based phylogenetic analyses of the neotropical tribe Helieae (Gentianaceae) are presented, including 22 of the 23 genera and 60 species. This study is based on data from morphology, palynology, and seed micromorphology (127 structural characters), and DNA sequences (matK, trnL intron, ITS). Phylogenetic reconstructions based on ITS and morphology provided the greatest resolution, morphological data further helping to tentatively place several taxa for which DNA was not available (Celiantha, Lagenanthus, Rogersonanthus, Roraimaea, Senaea, Sipapoantha, Zonanthus). Celiantha, Prepusa and Senaea together appear as the sister clade to the rest of Helieae. The remainder of Helieae is largely divided into two large subclades, the Macrocarpaea subclade and the Symbolanthus subclade. The first subclade includes Macrocarpaea, sister to Chorisepalum, Tachia, and Zonanthus. Irlbachia and Neblinantha are placed as sisters to the Symbolanthus subclade, which includes Aripuana, Calolisianthus, Chelonanthus, Helia, Lagenanthus, Lehmanniella, Purdieanthus, Rogersonanthus, Roraimaea, Sipapoantha, and Symbolanthus. Generic-level polyphyly is detected in Chelonanthus and Irlbachia. Evolution of morphological characters is discussed, and new pollen and seed characters are evaluated for the first time in a combined morphological-molecular phylogenetic analysis.

BACKGROUND: This report focuses on the common protocol developed by the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) for population‐based surveillance of Duchenne and Becker muscular dystrophy (DBMD) among 4 states (Arizona, Colorado, Iowa, and New York).METHODS: The network sites have developed a case definition and surveillance protocol along with software applications for medical record abstraction, clinical review, and pooled data. Neuromuscular specialists at each site review the pooled data to determine if a case meets the case criteria. Sources of potential cases of DBMD include neuromuscular specialty clinics, service sites for children with special healthcare needs, and hospital discharge databases. Each site also adheres to a common information assurance protocol. RESULTS: A population‐based surveillance system for DBMD was created and implemented in participating states. CONCLUSIONS: The development and implementation of the population‐based system will allow for the collection of information that is intended to provide a greater understanding of DBMD prevalence and health outcomes. Birth Defects Research (Part A) 2006. © 2006 Wiley‐Liss, Inc.

The inherited myopathies are a diverse group of disorders. The understanding of these diseases has grown dramatically in the past 10 years as a result of the rapidi dentification of causative genes. Two of the largest classes of inherited myopathies are the muscular dystrophies and the morphologically defined myopathies, including congenital myopathies. These diseases are typically diagnosed with either genetic testing or muscle biopsy. Treatment is supportive but involves management of multiple systems, including skeletal, cardiac, and respiratory systems.

We investigated attentional outcome after childhood stroke and orthopedic diagnosis in medical controls. Twenty-nine children with focal stroke lesions and individually matched children with clubfoot or scoliosis were studied with standardized attention and neuroimaging assessments. Stroke lesions were quite varied in location and commonly involved regions implicated in Posner's model of attention networks. Children with stroke lesions performed significantly more poorly regarding attention function compared with controls. Performance on the Starry Night, a test demanding alerting and sensory-orienting but not executive attention function, was significantly associated with lesion size in the alerting and sensory-orienting networks but not the executive attention network. Furthermore, earlier age at lesion acquisition was significantly associated with poorer attention function even when lesion size was controlled. These findings support the theory of dissociable networks of attention and add to evidence from studies of children with diffuse and focal brain damage that early insults are associated with worse long-term outcomes in many domains of neuropsychological function. In addition, these results may provide clues towards the understanding of mechanisms underlying attention in children. (JINS, 2004, 10, 976–986.)

We investigated the frequency and neurocognitive correlates of attention deficit hyperactivity disorder and traits of this disorder (ADHD/Traits) after childhood stroke and orthopedic diagnosis in medical controls. Twenty-nine children with focal stroke lesions and individually matched children with clubfoot or scoliosis were studied with standardized psychiatric, intellectual, academic, adaptive, executive, and motivation function assessments. Lifetime ADHD/Traits were significantly more common in stroke participants with no prestroke ADHD than in orthopedic controls (16/28 vs. 7/29; Fisher's Exact p &lt; .02). Lifetime ADHD/Traits in the orthopedic controls occurred exclusively in males with clubfoot (7/13; 54%). Participants with current ADHD/Traits functioned significantly worse (p &lt; .005) than participants without current ADHD/Traits on all outcome measures. Within the stroke group, current ADHD/Traits was associated with significantly lower verbal IQ and arithmetic achievement (p &lt; .04), more nonperseverative errors (p &lt; .005), and lower motivation (p &lt; .004). A principal components analysis of selected outcome variables significantly associated with current ADHD/Traits revealed “impaired neurocognition” and “inattention-apathy” factors. The latter factor was a more consistent predictor of current ADHD/Traits in regression analyses. These findings suggest that inattention and apathy are core features of ADHD/Traits after childhood stroke. This association may provide clues towards the understanding of mechanisms underlying the syndrome. (JINS, 2003, 9, 815–829.)

To evaluate the incidence of the facioscapulohumeral dystrophy (FSHD) 4q35 deletion in patients with facial-sparing scapular myopathy.

Summary: We report on four children who had cerebral vascular events in the first three months after the Fontan procedure for complex cyanotic congenital heart disease. Potential risk factors in these children included congestive heart failure, postoperative thrombocytosis, and cardiac arrhythmias. These cases suggest that children who undergo Fontan surgery may be at increased risk for cerebral infarction.

Facioscapulohumeral dystrophy is an autosomal dominant muscular dystrophy, the gene for which is localized to 4q35. It appears to be caused by deletion of tandem repeats that do not contain an expressed sequence. One current hypothesis is that the deletion affects expression of a centromeric gene (not yet identified) through a position effect. The mouse mutant, myodystrophy (myd, is a candidate model for facioscapulohumeral dystrophy. Mydhas a progressive muscular dystrophy and maps to a segment of mouse chromosome 8 that is syntenic with human 4q31–4q35.

Hypertensive encephalopathy is an uncommon but recognized complication of malignant hypertension in children. We reviewed the clinical course, laboratory studies, and outcomes of 12 patients with hypertensive encephalopathy seen at the University of Iowa Hospitals and Clinics between 1979 and 1994. The most common presenting symptoms were seizures, headache, and vision changes. Laboratory studies were nonspecific and in some patients were normal. Hypertensive encephalopathy is a clinical diagnosis. Management consists of recognition of this syndrome and aggressive treatment of hypertension. The neurologic outcome in our series was good. (J Child Neurol1996;11:193-196).

Cerebellar hypoplasia is found in association with a variety of neurologic and systemic disorders. It is the primary finding in the uncommonly reported condition of autosomal recessive cerebellar hypoplasia. We describe two siblings with cerebellar hypoplasia documented in both by magnetic resonance imaging (MRI) and review the clinical features of previously reported cases of autosomal recessive cerebellar hypoplasia. The most common findings in this disorder are nonprogressive ataxia, strabismus, mental retardation, and speech delay with dysarthria. Previously reported cases have been confirmed by autopsy, pneumoencephalography, or computed tomographic (CT) scans. MRI clearly documents diffuse cerebellar hypoplasia and aids in distinguishing autosomal recessive cerebellar hypoplasia from other disorders. The pathophysiology of this disorder is uncertain, however studies of the weaver mutant mouse (an animal model of autosomal recessive cerebellar hypoplasia) suggest that an abnormality of the Bergmann glia may lead to the observed granule cell layer deficiency in these patients. This diagnosis should be considered for children with nonprogressive ataxia and families should be made aware of the 25% recurrence risk. (JChild Neurol 1989;4:189-193).

Limb-girdle muscular dystrophy (LGMD) has been linked to 15 chromosomal loci, 7 autosomal-dominant (LGMD1A to E) and 10 autosomal-recessive (LGMD2A to J). To determine the distribution of subtypes among patients in the United States, 6 medical centers evaluated patients with a referral diagnosis of LGMD. Muscle biopsies provided histopathology and immunodiagnostic testing, and their protein abnormalities along with clinical parameters directed mutation screening. The diagnosis in 23 patients was a disorder other than LGMD. Of the remaining 289 unrelated patients, 266 had muscle biopsies sufficient for complete microscopic evaluation; 121 also underwent Western blotting. From this combined evaluation, the distribution of immunophenotypes is 12% calpainopathy, 18% dysferlinopathy, 15% sarcoglycanopathy, 15% dystroglycanopathy, and 1.5% caveolinopathy. Genotypes distributed among 2 dominant and 7 recessive subtypes have been determined for 83 patients. This study of a large racially and ethnically diverse population of patients with LGMD indicates that establishing a putative subtype is possible more than half the time using available diagnostic testing. An efficient approach to genotypic diagnosis is muscle biopsy immunophenotyping followed by directed mutational analysis. The most common LGMDs in the United States are calpainopathies, dysferlinopathies, sarcoglycanopathies, and dystroglycanopathies.

Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant disease of unknown pathogenesis which is characterized by weakness of the face and shoulder girdle. It is associated with a sensorineural hearing loss which may be subclinical. FSHD has been mapped to the distalmost portion of 4q35, although the gene has not yet been identified. Distal 4q has homology with a region of mouse chromosome 8 to which a mouse mutant, myodystrophy (myd), has been mapped. Muscle from homozygotes for the myd mutation appears dystrophic, showing degenerating and regenerating fibers, inflammatory infiltrates, central nuclei, and variation in fiber size. Brainstem auditory evoked potentials reveal a sensorineural hearing loss in myd homozygotes. Based on the homologous genetic map locations, and the phenotypic syndrome of dystrophic muscle with sensorineural hearing loss, we suggest that myd represents an animal model for the human disease FSHD.