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Background: Semaphorins and plexins are ligands and cell surface receptors that regulate multiple neurodevelopmental processes such as axonal growth and guidance. PLXNA3 is a plexin gene located on the X chromosome that encodes the most widely expressed plexin receptor in fetal brain, plexin-A3. Plexin-A3 knockout mice demonstrate its role in semaphorin signaling in vivo. The clinical manifestations of semaphorin/plexin neurodevelopmental disorders have been less widely explored. This study describes the neurological and neurodevelopmental phenotypes of boys with maternally inherited hemizygous PLXNA3 variants. Methods: Data-sharing through GeneDx and GeneMatcher allowed identification of individuals with autism or intellectual disabilities (autism/ID) and hemizygous PLXNA3 variants in collaboration with their physicians and genetic counselors, who completed questionnaires about their patients. In silico analyses predicted pathogenicity for each PLXNA3 variant. Results: We assessed 14 boys (mean age, 10.7 [range 2 to 25] years) with maternally inherited hemizygous PLXNA3 variants and autism/ID ranging from mild to severe. Other findings included fine motor dyspraxia (92%), attention-deficit/hyperactivity traits, and aggressive behaviors (63%). Six patients (43%) had seizures. Thirteen boys (93%) with PLXNA3 variants showed novel or very low allele frequencies and probable damaging/disease-causing pathogenicity in one or more predictors. We found a genotype-phenotype correlation between PLXNA3 cytoplasmic domain variants (exons 22 to 32) and more severe neurodevelopmental disorder phenotypes (P < 0.05). Conclusions: We report 14 boys with maternally inherited, hemizygous PLXNA3 variants and a range of neurodevelopmental disorders suggesting a novel X-linked intellectual disability syndrome. Greater understanding of PLXNA3 variant pathogenicity in humans will require additional clinical, computational, and experimental validation.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is characterized by triad of progressive cerebellar ataxia, progressive spasticity, and axonal/demyelinating peripheral neuropathy. Other manifestations include dysarthria, weakness in lower extremities and distal muscle wasting, foot deformities, retinal striation, prolapse of the mitral valve and rarely intellectual disability, hearing loss, and myoclonic epilepsy. We describe a patient who developed peripheral sensorimotor neuropathy in the absence of spasticity on initial presentation. He had nerve root enhancement on magnetic resonance imaging (MRI) lumbar spine, and nerve conduction studies were suggestive of demyelinating polyneuropathy. Patient had mild cerebellar atrophy on MRI and some delay of motor milestones. Over the course of several months, he developed spasticity, and genetic analysis together with clinical presentation was consistent with ARSACS. He was noted to have a pathogenic mutation c.8108GA (p. Arg2703His) inherited from mother and a variant of uncertain significance c.7216TC (p. Ser2406Pro) inherited from his father in

The US risdiplam expanded access program (EAP; NCT04256265) was opened to provide individuals with Type 1 or 2 spinal muscular atrophy (SMA) who had no satisfactory treatment options access to risdiplam prior to commercial availability. The program was designed to collect safety data during risdiplam treatment.Patients were enrolled from 23 non-preselected sites across 17 states and treated with risdiplam orally once daily. Eligible patients had a 5q autosomal recessive Type 1 or 2 SMA diagnosis, were aged ≥2 months at enrollment, and were ineligible for available and approved SMA treatments or could not continue treatment due to a medical condition, lack/loss of efficacy, or the COVID-19 pandemic.Overall, 155 patients with Type 1 (n = 73; 47.1%) or 2 SMA (n = 82; 52.9%) were enrolled and 149 patients (96.1%) completed the EAP (defined as obtaining access to commercial risdiplam, if desired). The median treatment duration was 4.8 months (range, 0.3-9.2 months). The median patient age was 11 years (range, 0-50 years), and most patients (n = 121; 78%) were previously treated with a disease-modifying therapy. The most frequently reported adverse events were diarrhea (n = 10; 6.5%), pyrexia (n = 7; 4.5%), and upper respiratory tract infection (n = 5; 3.2%). The most frequently reported serious adverse event was pneumonia (n = 3; 1.9%). No deaths were reported.In the EAP, the safety profile of risdiplam was similar to what was reported in pivotal risdiplam clinical trials. These safety data provide further support for the use of risdiplam in the treatment of adult and pediatric patients with SMA.

INTRODUCTION: Data on combining molecular therapies that increase survival motor neuron protein for spinal muscular atrophy type 1 (SMA1) is lacking. METHODS: This was a retrospective study describing our centers' experiences in treating SMA1 patients with combination therapy. RESULTS: Five children received nusinersen and onasemnogene abeparvovec-xioi (onasemnogene). Four were receiving nusinersen prior to onasemnogene. Nusinersen was continued in three. Marked liver enzyme elevations resulted in prolonged corticosteroid treatment in two patients with hospitalization and liver biopsy in one; milder liver enzyme elevations were noted in the other two. One patient received onasemnogene first, and then nusinersen. No adverse effects were noted. All patients improved. DISCUSSION: Combination molecular therapy is tolerated in SMA1 patients. Further studies are needed to determine whether there are circumstances in which combination therapy would be more efficacious than either monotherapy. Prolonged corticosteroid use and liver toxicity monitoring may be necessary with onasemnogene therapy. This article is protected by copyright. All rights reserved.

Bcl-2-associated athanogene 3 (BAG3) myopathy is a rare myofibrillar myopathy characterized by toe walking and clumsiness in the first decade with rapid progression to cardiomyopathy and restrictive lung disease in the second decade. Most patients (18 patients) have the c.626C >T (p.Pro209Leu) mutation. We describe BAG3 myopathy due to p.Pro209Leu in a 13-year-old girl with initial prominent neuropathic phenotype and no cardiac or respiratory involvement. Parents reported toe walking and clumsiness since 3 years old. Examination at the age of 13 years showed findings suggestive of Charcot-Marie-Tooth disease. Nerve conduction studies revealed demyelinating polyneuropathy. Next-generation sequencing panel for inherited neuropathies was unrevealing. Whole exome sequencing identified a de novo mutation in BAG3. Muscle biopsy confirmed myofibrillar myopathy. No cardiac involvement or symptoms of respiratory involvement at the age of 14 years. This case emphasizes the phenotypic variability of BAG3 myopathy and the importance of thorough electrophysiological examination and muscle pathology for establishing a precise diagnosis.

A 74-year-old man with no relevant medical history presented with 5 years of slowly progressive bilateral foot drop. He had used ankle foot orthoses for 3 years prior to presentation. There was no report of upper extremity weakness, numbness, paresthesia, myalgias, muscle cramps, or stiffness. He had attained age-appropriate developmental milestones as a child and was athletic, keeping up with his peers. His mother had bilateral foot drop, ankle contractures, and difficulty with ambulation. His brother, 2 daughters, and a son lacked similar symptoms. Neurologic examination showed bilateral distal lower extremity weakness (Medical Research Council grade 0/5 ankle dorsiflexion and eversion and grade 4/5 ankle plantar flexion and inversion), symmetric distal leg and intrinsic foot muscle wasting, absent patellar and Achilles tendon reflexes, and a steppage gait. Tone was reduced at bilateral ankles. Sensory examination including light touch, pinprick, vibration, and proprioception was intact. Mild bilateral pes cavus and hammertoes were noted. The remainder of the neurologic and physical examination was normal.

Introduction Clinical trials data concerning use of nusinersen in older spinal muscular atrophy (SMA) patients is lacking. We describe our center's experience in using intrathecal nusinersen for older patients in the clinical setting. Methods Retrospective study. Results Twelve patients (12-52 years old) were treated with nusinersen. Mean follow-up duration was 17.4 months (range, 4-26 months). All patients had scoliosis; 10 had spinal fusion/instrumentation. All procedures (30 cervical and 57 lumbar punctures) were technically successful. The only side effects were postprocedural headache (9%) and site pain (5.7%). Functional assessments showed stability in 6/9 patients and improvement in 3/9 patients. Subjective improvements in endurance, hand strength, and bulbar functioning critical for activities of daily living were reported in 8/12 patients. None of the patients has discontinued treatment so far. Discussion Intrathecal nusinersen can be safely delivered in older SMA patients. Available functional outcome measures are not adequate to capture meaningful subjective improvements.

Foot drop is common in chronic inflammatory demyelinating polyneuropathy (CIDP), but its prognosis is uncertain.CIDP patients with less than anti-gravity strength (3/5 power) of ankle dorsiflexion (ADF) on Medical Research Council manual muscle testing on presentation at our center were identified by retrospective review. After initiation of standard treatment, ADF power was serially tabulated, and predictors of recovery were determined.Of the 27 identified patients, ADF power at presentation was3/5 in 48/54 legs. At 1 y after treatment, ADF power improved to/= 3/5 in 17/27 patients in one (N = 6) or both (N = 11) legs. On multi-variate analysis, predictors of recovery of ADF power were tibialis anterior compound muscle action potential amplitude at presentation, shorter disease duration, and female gender.Foot drop improves to anti-gravity power in most treated CIDP patients depending in part on the severity of fibular motor axon loss at onset of treatment.

A 6-year-old biracial (Black and White) boy presented with worsening muscle twitching and stiffness. He had normal birth and development. His family noticed muscle twitching involving his thighs when he was 3 years old. Over the next 3 years, twitching spread to involve shoulders, chest, lower back, arms, and lower legs. The patient would feel muscle twitching underneath his skin and at times, these could be visible. His symptoms were worse with cold exposure. Recently, he started experiencing difficulties with fine motor activities such as writing, holding pencils, tying shoelaces, and buttoning. The patient denied myalgia, weakness, rhabdomyolysis, and paresthesias. Medical history includes well-controlled asthma, allergic rhinitis, right hydrocelectomy, and a small bowel intussusception. Family history was unremarkable. Neurologic examination revealed increased appendicular muscle tone, fasciculations involving upper and lower extremities, anterior chest, and paraspinal muscles, mild difficulty releasing hand grip, nasal dysarthria, and bilateral tight heel cords. Sensory examination, reflexes, and gait including heel and toe walking were normal.

The prevalence of coronavirus disease 2019 (COVID‐19) is lower in children compared to adults. Children contribute to 1‐5% of all COVID‐19 cases (1) . A recent study from China reported that 171(12.3%) of 1391 children with suspected disease had confirmed COVID‐19 infection (2) . As of May 15, 2020, there are 33,241 children with COVID‐19 in the United States (3) . The most common symptoms in children with confirmed and suspected COVID‐19 include fever and cough followed by diarrhea, and abdominal pain.

The coronavirus disease 2019 (COVID‐19) pandemic has resulted in the reorganization of health‐care settings affecting clinical care delivery to patients with Duchenne and Becker muscular dystrophy (DBMD) as well as other inherited muscular dystrophies. The magnitude of the impact of this public health emergency on the care of patients with DBMD is unclear as they are suspected of having an increased risk for severe manifestations of COVID‐19. In this article, the authors discuss their consensus recommendations pertaining to care of these patients during the pandemic. We address issues surrounding corticosteroid and exon‐skipping treatments, cardiac medications, hydroxychloroquine use, emergency/respiratory care, rehabilitation management, and the conduct of clinical trials. We highlight the importance of collaborative treatment decisions between the patient, family, and health‐care provider, considering any geographic or institution‐specific policies and precautions for COVID‐19. We advocate for continuing multidisciplinary care for these patients using telehealth.

The coronavirus disease 2019 (COVID‐19) pandemic has resulted in reorganization of healthcare settings affecting the delivery of clinical care to patients with spinal muscular atrophy (SMA). There is a concern that patients with SMA may be at increased risk of manifesting severe symptoms of COVID‐19. Currently approved therapies for SMA improve survival and motor function; however, their delivery requires an increased exposure to the health system and a dedicated healthcare team. In this study, we discuss consensus recommendations pertaining to care of SMA patients during the pandemic. We highlight that SMA treatments should not be perceived as elective. Decisions regarding the delay of treatments should be made with consideration of the potential risks of COVID‐19 exposure and the risk of that delay. We emphasize the importance of collaborative treatment decisions between the patient, family, and healthcare provider, considering any geographic‐ or institution‐specific policies and precautions for COVID‐19.

We describe a 10-month-old boy with early-onset epileptic encephalopathy who was found to have a hemizygous deletion in 9q33.3-q34.11 involving STXBP1 and SPTAN1 genes. He presented at the age of 2.5 months with frequent upper extremity myoclonus, hypotonia, and facial dysmorphisms. Interictal EEG showed multifocal polyspike and wave during wakefulness and sleep. Ictal EEG revealed low-amplitude generalized sharp slow activity, followed by diffuse attenuation. Metabolic testing was unrevealing. Brain MRI showed thinning of the corpus callosum with an absence of rostrum. This patient is the second reported case with 9q33.3-q34.11 deletion involving STXBP1 and SPTAN1 genes associated with epileptic encephalopathy and myoclonic seizures. Larger case series are needed to better delineate this association.

Background Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder involving brainstem, pons in particular, characterized by a predominant T-cell pathology and responsiveness to glucocorticosteroids. We describe a difficult 6 year course of this rare syndrome in a 10-year-old girl. Case report Our patient presented with diplopia, spastic paraparesis, and unsteady gait. MRI showed characteristic punctate hyper-intensities with enhancement in the brain stem, cerebellar peduncles, and optic chiasm and diffuse nodular enhancement throughout the cervical and thoracic spinal cord. Brain biopsy revealed perivascular inflammatory lesions compatible with CLIPPERS. Pulse intravenous methylprednisolone followed by oral prednisolone resulted in significant clinical improvement. She had multiple clinical relapses associated with new brain and/or spinal cord lesions despite sequential maintenance methotrexate and rituximab with low dose steroids. Each relapse responded to pulse steroids. Conclusion Her overall clinical course was progressive but responsive to pulse steroids. Long-term treatment remains challenging.

Objective: Cranial computed tomography (CT) is not recommended in the routine evaluation of children with first afebrile seizure due to its low yield. The objective was to assess the current practice in our pediatric emergency department regarding the use of head CT in children with first afebrile seizure and to identify the factors that lead to ordering a head CT. Methods: Medical records of patients between 1 month and 18 years old evaluated at our emergency department for presentation of first afebrile seizure between 2010 and 2014 were retrospectively reviewed. Data extracted include age, gender, seizure type, single or multiple seizures at presentation, seizure duration, predisposing conditions to seizures (ie, history of developmental delay), and whether a head CT was performed. Contingency tables with chi-square analyses were used to determine which variables were associated with increased use of head CT. Results: Of 155 patients (88M/67F) included in the study, 72 (46.5%) underwent head CT and only 3 had clinically significant findings that did not require acute management. There were no differences in CT use by age, sex, seizure type, seizure number, seizure risk factors, or findings on physical examination. Head CT was performed more frequently in cases with seizures ≥5 minutes and unknown seizure duration ( P = .04). Conclusion: Despite existing evidence, the emergent head CT rate was high in our cohort. Children with seizure duration of ≥5 minutes or of unknown duration were more likely to undergo head CT in our emergency department.

Nonketotic Hyperglycinemia is an autosomal recessive disorder characterized by defects in the mitochondrial glycine cleavage system. Most patients present soon after birth with seizures and hypotonia, and infants that survive the newborn period often have profound intellectual disability and intractable seizures. Here we present a case report of a 4-year-old girl with NKH as well as hyperammonemia, an uncommon finding in NKH. Genetic analysis found a previously unreported homozygous mutation (c.878–1 G > A) in the AMT gene. Maximum Entropy Principle modeling predicted that this mutation most likely breaks the splice site at the border of intron 7 and exon 8 of the AMT gene. Treatment with L-Arginine significantly reduced both the proband’s glycine and ammonia levels, in turn aiding in control of seizures and mental status. This is the first time the use of L-Arginine is reported to successfully treat elevated glycine levels.

ObjectiveTo report our experience delivering intrathecal nusinersen through cervical puncture in patients with spinal muscular atrophy (SMA) with no lumbar access.BackgroundSMA is a neuromuscular disorder characterized by profound muscle weakness, atrophy, and paralysis due to degeneration of the anterior horn cells. Nusinersen, the first Food and Drug Administration–approved treatment for SMA, is administered intrathecally via lumbar puncture; however, many patients with SMA have scoliosis or solid spinal fusion with hardware that makes lumbar access impossible. Studies in primates have demonstrated better spinal cord tissue concentration with intrathecal injections than with intracerebral ventricular injections. Therefore we have used C1/C2 puncture as an alternative to administer nusinersen.MethodRetrospective chart review.ResultsIntrathecal nusinersen via cervical puncture was given to 3 patients who had thoracic and lumbosacral spinal fusion: a 12-year-old girl with type 1 SMA and 2 17-year-old girls with type 2 SMA. Cervical puncture was performed without deep sedation under fluoroscopic guidance using a 25-G or a 24-G Whitacre needle in the posterior aspect of C1-C2 interspace and full dose of nusinersen (12 mg/5 mL) was injected after visualizing free CSF flow. Patients completed their 4 loading doses and first maintenance dose of nusinersen, and 15 procedures were successful and well-tolerated.ConclusionCervical puncture is a feasible alternative delivery route to administer intrathecal nusinersen in patients with longstanding SMA and spine anatomy precluding lumbar access when done by providers with expertise in this procedure.

Summary Purpose There is a gap in our knowledge of the factors that modulate the predisposition to seizures following perinatal hypoxia. Herein, we investigate in a mouse model the effects of two distinct factors: developmental stage after the occurrence of the perinatal insult, and the presence of a seizure predisposing mutation. Methods Effects of age: P6 (postnatal day 6) mouse pups were subjected to acute hypoxia down to 4% O2 over the course of 45 min. Seizure susceptibilities to flurothyl-induced seizures (single exposures) and to flurothyl kindling were determined at specific subsequent ages. Effects of mutation: Heterozygote mice, with deletion of one copy of the Kcn1a gene, subjected to P6 hypoxia were compared as adults to wild-type mice with respect to susceptibility to a single exposure to flurothyl and to the occurrence of spontaneous seizures as detected by hippocampal electroencephalography (EEG) and video recordings. Key Findings Effects of age: As compared to controls, wild-type mice exposed to P6 hypoxia had a shortened seizure latency in response to a single flurothyl exposure at P50, but not at P7 or P28 (p

We describe the electroencephalographic and clinical seizure manifestations of pyridoxal 5'-phosphate-dependent epilepsy (PLP-DE) in two patients [diagnosis confirmed by low cerebrospinal fluid (CSF) PLP, complete resolution of previously intractable seizures with PLP supplementation, negative pyridoxine-dependent epilepsy CSF biomarkers, and/or positive disease causing pyridox(am)ine 5'-phosphate oxidase gene mutation] along with a comprehensive review of the literature. One patient presented with neonatal tonic status epilepticus with subsequent generalized tonic-clonic seizures, and the second, with refractory complex partial seizures starting at 2 years of age. The pretreatment EEG revealed, interictally, burst suppression, multifocal independent sharp waves, and electrical status epilepticus in sleep. Ictally and interictally, it revealed runs of unilateral spike/slow waves. Previously reported features include burst suppression, myoclonus, tonic seizures, clonic seizures, and spasms. In the appropriate clinical scenario, the aforementioned features should raise the possibility of PLP-DE and appropriate treatment should be initiated. The first late-onset case (at 2 years) of PLP-DE is reported.

Seizure semiology and electroencephalographic (EEG) manifestations of autoimmune-mediated cerebral folate deficiency (CFD) before and after therapy have yet to be fully characterized. Here, we report these findings in two such patients. Our first patient presented with the novel manifestation of infantile spasms at the age of 3months, while the second developed the previously reported initial onset of tonic seizures with static developmental delay, but subsequently manifested the novel finding of electrical status epilepticus in sleep at the age of 15years. Awareness of these new manifestations, together with the previously reported manifestations of developmental delay, seizure onset during the first 2years of life, occurrence of tonic, myoclonic-astatic, absence, and generalized tonic-clonic seizures, with an EEG of generalized spike-slow waves and multifocal spikes, is important to increase the index of suspicion of this treatable disorder.

Oxcarbazepine has been reported to precipitate myoclonic, generalised tonic-clonic, absence, and complex partial seizures, and carbamazepine to precipitate absences, myoclonic seizures and spasms. Here, we report a one-year, six-month-old girl with complex partial seizures who developed infantile spasms, developmental regression, and hypsarrhythmia during the two weeks directly following initiation of oxcarbazepine (14 mg/kg/day). All of these resolved within a few days after discontinuation of this medication. Although we cannot rule out that the above association may have been coincidental, or that the improvement may have been due to concurrent therapy, this case raises the possibility that oxcarbazepine, like carbamazepine, may precipitate infantile spasms and West syndrome.

We describe two boys whose distinct and remarkable clinical pictures suggested the possibility of anti-N-methyl-d-aspartate receptor antibody encephalitis. Both patients responded to immunotherapy, but neither manifested that antibody. Patient 1 exhibited florid encephalopathy with psychotic manifestations including inappropriate affect, intermittent delirium, visual hallucinations, severe anorexia, agitation, paranoid ideation, and abnormal electroencephalogram results. He responded to intravenous immunoglobulin, with steady improvement over 3 months to almost complete remission for 1 year, followed by a relapse that again responded, more quickly, to intravenous immunoglobulin. A second relapse occurred 1 month later, and again responded to intravenous immunoglobulin. Patient 2 exhibited progressive, severely debilitating limb dystonia that worsened over 1.5 years, with milder psychiatric symptoms including mood instability, aggressiveness, impulsivity, and depression. When he developed thymic hyperplasia 1.5 years into his illness, he underwent a thymectomy, and improved significantly on a regimen of plasmapheresis and intravenous immunoglobulin. Patients presenting with symptoms suggestive of autoimmune encephalitis, but without antibodies, may still respond to immunotherapy.

We report four patients with no preexisting movement disorders who developed oculogyric crises secondary to lamotrigine toxicity and had resolution of these crises after dose reduction. Episode numbers ranged from 1-20 per day and episode duration from 2 s to several hours. Mean plasma concentration of lamotrigine at the time of oculogyric crisis was 15.5 μg/mL, with a mean dose of 16 mg/kg per day.

The superior longitudinal fasciculus (SLF) II and cingulum are two white matter tracts important for attention and other frontal lobe functions. These functions are often disturbed in children with drug-resistant (DR) partial epilepsy, even when no abnormalities are seen on conventional MRI. We set out to determine whether abnormalities in these structures might be depicted on diffusion tensor imaging (DTI) studies in the absence of abnormalities on conventional MRI. We compared the DTI findings of 12 children with DR partial epilepsy with those of 12 age- and gender-matched controls. We found that the SLF II fractional anisotropy (FA) values of the patients were significantly lower than those of the controls (means: 0.398±0.057 and 0.443±0.059, respectively, P=0.002). Similarly, apparent diffusion coefficient (ADC) and parallel diffusivity values for SLF II were also significantly lower in the patients. There were no differences in the FA and ADC values of the cingulum. Our findings are consistent with abnormal structural connectivity of the frontal lobe in children with DR partial epilepsy and provide a possible explanation for the previously reported functional abnormalities related to the SLF II in these patients.

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with numerous and variable clinical manifestations including conotruncal heart abnormalities, palatal anomalies, hypoparathyroidism, immune deficiency, and cognitive deficits. The clinical suspicion of this syndrome is often heightened by the presence of characteristic facial features. A previous report highlighted the under-diagnosis of this condition in African Americans, thought to be related to a paucity of typical facial features. We ascertained the largest cohort (n = 50) of African-American individuals with 22q11DS reported thus far, across five genetics centers in the United States and report on their facial and other phenotypic features. About 3/4 of our cohort has at least one dysmorphic facial feature. Auricular abnormalities, especially small ears, are the most common dysmorphic facial feature followed by nasal and ocular abnormalities. Skeletal findings are seen in about 2/3 of our cohort, higher than the typical frequency reported in 22q11DS. Cardiac anomalies, developmental delay, and palatal abnormalities are seen at a lower frequency in our cohort. Thus, it is evident that the features traditionally associated with 22q11DS are difficult to recognize in African-American individuals with this syndrome, due to both altered frequencies of major anomalies and a non-classic facial appearance. Therefore, a high index of suspicion is needed to recognize 22q11DS in African-American individuals.

To report our experience with cephalometry in evaluating velopharyngeal dysfunction (VPD) in velocardiofacial syndrome (VCFS) and its utility in assessing the role of cervical spine abnormalities in VPD, prior to surgical correction of VPD.Clinical charts and cephalometric radiographs done prior to surgery for VPD were retrospectively analyzed to ascertain velopharyngeal measurements and cervical spine abnormalities.Twenty-six patients (age: 6-23 years) with molecularly confirmed VCFS.Wake Forest University Health Sciences (1997-2005).Cranial base angle, nasopharyngeal depth, velum length, and Need ratio at rest, velar dimple location, and velopharyngeal length during phonation; information on presence/absence of submucous cleft palate and cervical spine abnormalities were also obtained. The relationship between C1 anterior arch abnormalities and Need ratio was examined.Seventy-three percent of the VCFS patients had excessive nasopharyngeal depth, 80% had an abnormal Need ratio, 50% had a short velum, 81% had a submucous or occult submucous cleft palate, 90.5% had a cervical spine abnormality (C1 anterior arch abnormalities in 38%) and 11.5% had platybasia. There was a significant difference in the Need ratio between patients with and without C1 anterior arch abnormalities.Cephalometry can be used to delineate factors such as C1 vertebral abnormalities, excessive pharyngeal depth, and short velum that contribute to VPD in VCFS. This would help otolaryngologists better understand the anatomy prior to surgical treatment of VPD. This is the first study to highlight the frequent occurrence of C1 anterior arch abnormalities in VCFS.

We report an adult male with 22q11.2 deletion syndrome and a germline BRCA2 mutation who developed T-cell monoclonal lymphoid proliferation involving the skin and a polyclonal proliferation of a retroperitoneal lymph node without any identifiable infectious and inflammatory causes. This is the first report of reactive lymphoid hyperplasia in the setting of co-occurrence of 22q11.2 deletion syndrome and a BRCA2 mutation. Further cases with a similar presentation should be reported and studies should be directed to identify the possible mechanisms involved.