Early Identification of DMD in the Setting of West Syndrome

Duchene muscular dystrophy (DMD) is the most common muscular dystrophy in childhood, affecting ∼1:5000 male live births worldwide. DMD is a genetic disorder with X-linked recessive inheritance pattern characterized by a severe muscular phenotype with progressive muscle weakness and atrophy due to pathogenic variations within the DMD gene. Two cases are reported to date in the literature of individuals with a diagnosis of both DMD and West syndrome; neither of which had the degree of additional genetic abnormalities that our patient demonstrates. We present a male infant with West syndrome, and multiple pathogenic variants, the ominous one being in the DMD gene. This case adds to confirming that West syndrome expands the spectrum of epilepsy that may be present in DMD patients. Additionally, this case can identify how the early use of steroids may shed light on effects of early symptomatic treatment of DMD.

Orthostatic Headaches Associated With Spontaneous Intracranial Hypotension and Autonomic Dysfunction—A Case Series in Young Patients

Background: Orthostatic headaches can be noted in spontaneous intracranial hypotension and orthostatic intolerance. We present a case series of young patients diagnosed with spontaneous intracranial hypotension and were treated for the same but subsequently developed orthostatic intolerance. Methods: We retrospectively reviewed charts for seven young patients with orthostatic headaches related to spontaneous intracranial hypotension and orthostatic intolerance. Results: Patients were diagnosed with spontaneous intracranial hypotension. Diagnosis was confirmed by identifying epidural contrast leakage and three of seven patients were noted to have early renal contrast excretion on computerized tomography myelography. Patients were treated with epidural blood patches. All patients showed persistent symptoms of autonomic dysfunction after treatment of spontaneous intracranial hypotension and orthostatic intolerance was confirmed with head-up tilt table test. Conclusions: Patients with spontaneous intracranial hypotension failing to improve following epidural blood patching should be evaluated for orthostatic intolerance.

Expanding Phenotype of ATP1A3 - Related Disorders: A Case Series

Neurologic disorders caused by mutations in the ATP1A3 gene were originally reported as three distinct rare clinical syndromes: Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP) and Cerebellar ataxia, Areflexia, Pes cavus, Opticus atrophy and Sensorineural hearing loss (CAPOS). In this case series, we describe 3 patients. A mother and her daughter showed an intermediate phenotype different from each other with the same heterozygous missense mutation (p.[R756C]), recently described in literature as Relapsing Encephalopathy With Cerebellar Ataxia (RECA). In addition, a third patient showed an intermediate AHC-RDP phenotype and had a likely pathogenic novel de novo missense mutation (p.[L100 V]). These patients support the growing evidence that AHC, RDP and RECA are part of a continuous ATP1A3 mutation spectrum that is still expanding. Three common features were a sudden onset, asymmetrical neurological symptoms, as well as the presence of triggering factors. When present, the authors argue to perform exome sequencing in an early stage.

Novel HSD17B4 Variants Cause Progressive Leukodystrophy in Childhood: Case Report and Literature Review

D-bifunctional protein (DBP) deficiency is a peroxisomal disorder with a high degree of phenotypic heterogeneity. Some patients with DBP deficiency develop progressive leukodystrophy in childhood. We report a 6-year-old boy with moderate hearing loss who presented with developmental regression. Brain magnetic resonance imaging demonstrated progressive leukodystrophy. However, very long chain fatty acids (VLCFAs) in the plasma were at normal levels. Whole-exome sequencing revealed compound heterozygous variants in HSD17B4 (NM_000414.3:c.[350A > T];[394C > T], p.[[Asp117Val]];[[Arg132Trp]]). The c.394C > T variant has been identified in patients with DBP deficiency and is classified as likely pathogenic, while the c.350A > T variant was novel and classified as uncertain significance. Although one of the two variants was classified as uncertain significance, an accumulation of phytanic and pristanic acids was identified in the patient, confirming type III DBP deficiency. DBP deficiency should be considered as a diagnosis in children with progressive leukodystrophy and hearing loss even if VLCFAs are within normal levels.

Pitt Hopkins-Like Syndrome 1 with Novel CNTNAP2 Mutation in Siblings

Pitt Hopkins-like syndrome 1 (PTHLS1, OMIM # 610042) is an ultra-rare autosomal recessive condition with a prevalence of <1/1,000,000. Intragenic deletions of CNTNAP2 has been implicated in PTHLS1, however to our knowledge a compound heterozygous deletion of exon 4 and a c.1977_1989del13; p.V660Ffsx9 frameshift variant have not been published previously. In this case report, the proband is a seven year old female with PTHLS1, developmental delay, autism spectrum disorder, focal epilepsy, hypotonia, refractory errors, strabismus, and obstructive sleep apnea. Whole exome sequencing analysis revealed biallelic pathogenic variants of the CNTNAP2 gene. Proband has a three year old sister who has who has a similar phenotype including, developmental delay, epilepsy, gait abnormality, refractory errors, strabismus. Family variants were tested and she shared the same CNTNAP2 variants as her sister. The sisters described highlight two novel variants leading to PTHLS1. Genetic workup is essential in identification and management guidance in these populations.

Patients With Extreme Early Onset Juvenile Huntington Disease Can Have Delays in Diagnosis: A Case Report and Literature Review

Huntington disease (HD) is caused by a pathologic cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. Typical adult-onset disease occurs with a minimum of 40 repeats. With more than 60 CAG repeats, patients can have juvenile-onset disease (jHD), with symptom onset by the age of 20 years. We report a case of a boy with extreme early onset, paternally inherited jHD, with symptom onset between 18 and 24 months. He was found to have 250 to 350 CAG repeats, one of the largest repeat expansions published to date. At initial presentation, he had an ataxic gait, truncal titubation, and speech delay. Magnetic resonance imaging showed cerebellar atrophy. Over time, he continued to regress and became nonverbal, wheelchair-bound, gastrostomy-tube dependent, and increasingly rigid. His young age at presentation and the ethical concerns regarding HD testing in minors delayed his diagnosis.

How Providers in Child Neurology Transitioned to Telehealth During COVID-19 Pandemic

To understand child neurology care practices in telehealth (TH), we conducted an online survey interested in identifying which patients should be triaged for in-person evaluations in lieu of telehealth management. We also sought to identify provider and patient/parent limitations of the TH experience. One hundred fourteen clinicians completed the online survey. The majority of child neurologists transitioned within 3 weeks of the pandemic onset and found it inappropriate to evaluate a child under 1 year of age via TH. We identified specific disorders considered inappropriate for initial evaluation via TH, including neuromuscular disease, neuropathy, weakness, autoimmune disease and autism spectrum disorders. Patient and parent technical and economic issues are significant limitations of TH. We suggest quality improvement measures to provide additional training, focusing on particular disorders and increased access for those patients currently excluded from or limited in using or accessing TH.

A Case Report of a Prenatally Missed Mowat-Wilson Syndrome With Isolated Corpus Callosum Agenesis

Mowat–Wilson syndrome (MWS) is an autosomal dominant genetic disorder caused by ZEB2 gene mutations, manifesting with unique facial characteristics, moderate to severe intellectual problems, and congenital malformations as Hirschsprung disease, genital and ophthalmological anomalies, and congenital cardiac anomalies. Herein, a case of 1-year-old boy with isolated agenesis of corpus callosum (IACC) in the prenatal period is presented. He was admitted postnatally with Hirschsprung disease (HSCR), hypertelorism, uplifted earlobes, deeply set eyes, frontal bossing, oval-shaped nasal tip, ‘‘M’’ shaped upper lip, opened mouth and prominent chin, and developmental delay. Hence, MWS was primarily considered and confirmed by the ZEB2 gene mutation analysis. His karyotype was normal. He had a history of having a prenatally terminated brother with similar features. Antenatally detected IACC should prompt a detailed investigation including karyotype and microarray; even if they are normal then whole exome sequencing (WES) should be done.

Keto-Sleuths – An Unusual Cause of Loss of Ketosis?

Ketogenic diets provide a non-pharmaceutical alternative for treatment of refractory epilepsy. When successful in reducing or eliminating seizures, medication numbers or doses may be reduced. Unexpected loss of ketosis is a common problem in management of patients on ketogenic diets and, especially when the diet is an effective treatment, loss of ketosis may be associated with an exacerbation in seizures. Identification of the cause of loss of ketosis is critical to allow rapid resumption of seizure control, and prevention of unnecessarily increased diet restriction or increased medication doses. Here an unusual environmental cause of loss of ketosis is described (contamination with starch-containing drywall dust), illustrating the extent of investigation sometimes necessary to understand the clinical scenario.

A Sense of Humor is Especially Important During Difficult Times

Artist-critic Clive James said: “Common sense and a sense of humor are the same thing, moving at different speeds. A sense of humor is just common sense, dancing. Those who lack humor are without judgment and should be trusted with nothing.”