Mild Speech Delay Research Articles

Mosaic Potocki-Lupski Syndrome Due to a Supernumerary Marker Chromosome Containing <i>RAI1</i>

Potocki-Lupski syndrome<strong> </strong>(PTLS) is a recurrent microduplication syndrome characterized by developmental delay, behavioral abnormalities, mildly dysmorphic facial features, hypotonia, and sleep disorders. We report here a 3-year-old girl diagnosed with mosaic PTLS harboring a supernumerary marker chromosome containing the <em>RAI1</em> (retinoic acid induced 1) gene. Cytogenetic testing, including chromosomal microarray, karyotype, and FISH analysis, identified a ring chromosome containing portions of chromosomes 14 and 17 in 85% of cells. Clinical features of this individual included atypical facies with frontal bossing, bitemporal narrowing, prominent cupped ears, and mild speech delay. Presented here is a novel case of PTLS associated with mosaic gains of chromosomes 14 and 17. As small supernumerary marker chromosomes (sSMCs) involving non-acrocentric chromosomes are rare, this case contributes to our understanding of phenotypic spectrum associated with sSMC(17).

C8 (Clinical Case) A 10-Month-Old Male with Macrocytic Anemia and Hypoalbuminemia

Abstract Introduction/Background Transcobalamin-II Deficiency (TCII-Deficiency) is a rare autosomal-recessive metabolic condition, resulting in ineffective transport and uptake of Vitamin B12. Clinical features of pancytopenia, failure to thrive, diarrhea, and developmental delay typically present between 1-12 months of age1. Case Description A 10-month-old term, previously well male with a normal newborn screen, presented with a one-month history of decreased energy, failure to thrive, and diarrhea. He had a two-week history of gross motor regression with lower limb and periorbital edema. Examination was notable for perioral rash, severe diaper dermatitis, buccal ulcerations, pallor, and generalised edema including ascites. There was no organomegaly or any dysmorphic features. Investigations revealed macrocytic anemia, thrombocytopenia, worsening neutropenia, hypoalbuminemia, hypertriglyceridemia, and hypogammaglobulinemia (Table 1). Vitamin B12 and B9 levels were normal. Bone marrow biopsy was hypocellular, and ruled out aplastic anemia and leukemia. Intestinal biopsy showed generalized edema from duodenum to rectum with GVHD-like injury pattern, and evidence for protein-losing enteropathy (PLE). Required therapy included numerous RBC, platelet, and albumin transfusions and enteral feeding. A disorder of vitamin B12 metabolism, specifically TCII-Deficiency, was suspected based on clinical presentation with no other clear explanation. Serum MMA was highly elevated at 24,154 nmol/L (0-500 nmol/L) as was homocysteine at 27.3 umol/L (4.7-10.3 umol/L). Whole-exome sequencing identified two mutations in TCN2. Treatment with intramuscular vitamin B12 resulted in reduction of urinary MMA level to 5.6 umol/mmol Cr (< 2 umol/mmol Cr) in 10 days. Discussion Over the next months of treatment with intramuscular hydroxocobalamin, the MMA, homocysteine, albumin and CBC normalized and all clinical complications were resolved. Gross motor skills returned to normal, with only mild persistent speech delay. TCII-Deficiency often presents with a heterogeneous constellation of symptoms. In this case, the differential included several hematologic and gastrointestinal pathologies, including DGAT1 deficiency (due to hypertriglyceridemia, diarrhea, and PLE) and CHAPLE syndrome (due to low immunoglobulins and PLE). MMA and homocysteine levels are often markedly elevated in B12 metabolism defects, and can justify initiation of treatment with cyanocobalamin/hydroxocobalamin (Vitamin B12) while awaiting confirmatory genetic testing2. Conclusion TCII-Deficiency is a rare cause of macrocytic anemia; early consideration and treatment with intramuscular vitamin B12 leads to dramatic symptom improvement and is important for paediatricians to recognize. Clinical Pearls: • Clinicians should consider B12 metabolism defects on their differential in a young child who has macrocytic anemia with normal B12 levels. • Paediatricians can use MMA and homocysteine levels to assess for B12 metabolism defects while awaiting genetic testing.

Proximal 15q11.2 Microduplication: A Case Report of Variable Expressivity

The four highly conserved and non- imprinted genes (NIPA1, NIPA2, CYFIP1 and TUBGCP5) are located on the proximal 15q in the region between BP1 and BP2 which spans approximately 500 kb. Here, we report on a paternally inherited 15q11.2 breakpoint 1-2 microduplication carrier with epilepsy, near-normal neurodevelopment, mild intellectual disability and speech delay. The father had a normal phenotype, suggesting the variable expressivity. Proximal 15q breakpoint 1-2 region copy number variants may not warrant a clinical outcome since the phenotypic variability and low penetrance. We believe that greater understanding of the possible underlying molecular, genetic, and environmental modifying factors of the copy number variants in this susceptibility locus will aid in our clinical approach.

An atypically mild case of ethylmalonic encephalopathy with pathogenic ETHE1 variant

Ethylmalonic encephalopathy (EE) is a rare, severe, autosomal recessive condition caused by pathogenic variants in ETHE1 leading to progressive encephalopathy, hypotonia evolving to dystonia, petechiae, orthostatic acrocyanosis, diarrhea, and elevated ethylmalonic acid in urine. In this case report, we describe a patient with only mild speech and gross motor delays, subtle biochemical abnormalities, and normal brain imaging found to be homozygous for a pathogenic ETHE1 variant (c.586G>A) via whole exome sequencing. This case highlights the clinical heterogeneity of ETHE1 mutations and the utility of whole-exome sequencing in diagnosing mild cases of EE.

P594: A 3.9 Mb triplication within 11p14.1p13 containing ELP4 and PAX6 in a patient with congenital nystagmus and mild speech delay

P594: A 3.9 Mb triplication within 11p14.1p13 containing ELP4 and PAX6 in a patient with congenital nystagmus and mild speech delay

THE ROLE OF VITAMIN D IN THE COURSE AND DEVELOPMENT OF SOME NEUROLOGICAL SYNDROMES

Over the past decade, many reports addressed the importance of vitamin D in the development of neurological, neurodegenerative and mental diseases. Nevertheless, there are many controversial and unresolved problems, contradictory opinions and data. The aim of the study was to determine the importance of vitamin D deficiency in the development and course of some neurological syndromes in children and adolescents. 150 patients aged 1 to 16 years were studied. According to the clinic, they were divided into following groups: A - mild mental and speech delay (17 patients); В - behavioral disorder (18); B1 - autistic spectrum disorder (13); C - Attention Deficit Hyperactivity Disorder (17); D - frequent headache (24); E - fatigue (19); F - insomnia (23); G - seizures (19). The research resulted in a couple of conclusions: 40% of patients with attention deficit hyperactivity disorder had got significantly lower levels of Vitamin D in each age group. Administering vitamin D (Aquadetrim) during 2.5 months reduced hyperactivity, aggression, improved memory and speech skills. 38% of patients with epilepsy who had been taking antiepileptic drugs for more than 3 years had low levels of vitamin D in their blood (11.4 to 16.5 ng / ml). However, prescribing high doses of vitamin D in combination with anticonvulsants might develop side effects, which makes it necessary to control vitamin D level during treatment. Low levels of vitamin D (13,4-18.8 ng / ml) were found in 28% of practically healthy children aged 6 to 16 years (control group). A detailed study of the anamnesis revealed frequent fatigue, periodic headaches, insomnia. Vitamin D deficiency has an important role in the pathogenesis of somatic and as well as neurological diseases, and its deficiency is difficult to diagnose due to polysymptomatic clinical manifestations, we consider it necessary to include vitamin D research in a routine (mandatory) analysis to determine its role in both acute and chronic diseases.

Storybook Literacy Method Increasing Language Development in Children with Speech Delay

Children's speaking ability is very important in their development. Stages in a child's language development sometimes experience delays and can become a nuisance. The most common and easily recognizable language disorder is speech delay, which means the child's level of speech development is not appropriate for his age. One of the actions that can be taken for children who have speech delays is the storybook literacy method. This method can help develop and train children's language skills and through stories children are required to be active in developing language. The purpose of the study was to determine the effectiveness of the storybook literacy method on language development in children with speech delay. This study uses the One Group pre-test and post-test design. Sampling technique using non-probability sampling saturated sampling type. The sample is 10 children with mild speech delay. The research instrument was using the Stimulation of Early Intervention Detection of Growth and Development (SDIDTK) instrument through the KPSP form. The analysis used is the T-Test. The results of the T-Test test obtained a p-value of 0.000, which means that there is an influence of the storybook literacy method on children's language development with speech delay. Storybook literacy method is effective to improve language development in children with speech delay.

Follow-up for a Preterm Infant with Beckwith-Wiedemann Syndrome.

Follow-up for a Preterm Infant with Beckwith-Wiedemann Syndrome.

MEIS2 (15q14) gene deletions in siblings with mild developmental phenotypes and bifid uvula: documentation of mosaicism in an unaffected parent

MEIS2 (Meis homeobox 2) encodes a homeobox protein in the three amino acid loop extension (TALE) family of highly conserved homeodomain-containing transcription regulators important for development. MEIS2 deletions/mutations have been associated with cleft lip/palate, dysmorphic facial features, cardiac defects, as well as intellectual disability at a variable severity. Here we report on one familial case that two affected siblings carry the same non-mosaic ~ 423 kb genomic deletion at 15q14 encompassing the entirety of CDIN1 and the last three exons (ex. 10, 11, 12) of the MEIS2 gene, while their unaffected father is mosaic for the same deletion in about 10% lymphocytes. Both siblings presented with mild developmental delay and bifid uvula, while no congenital cardiac abnormalities were identified. The elder sister also showed syncopal episodes and mild speech delay and the father had atrial septal defects. This is the first report showing multiple family members inherit a genomic deletion resulting in a MEIS2 partial truncation from a mosaic parent. Taken all together, this study has important implications for genetic counseling regarding recurrence risk and also points to the importance of offering MEIS2 gene tests covering both point mutations and microdeletions to individuals with milder bifid uvula and developmental delay.

A Novel Multi-Exon Deletion of PACS1 in a Three-Generation Pedigree: Supplements to PACS1 Neurodevelopmental Disorder Spectrum.

PACS1 neurodevelopmental disorder (PACS1-NDD) is a category of rare disorder characterized by intellectual disability, speech delay, dysmorphic facial features, and developmental delay. Other various physical abnormalities of PACS1-NDD might involve all organs and systems. Notably, there were only two unique missense mutations [c.607C > T (p.Arg203Trp) and c.608G > A (p.Arg203Gln)] in PACS1 that had been identified as pathogenic variants for PACS1-NDD or Schuurs-Hoeijmakers syndrome (SHMS). Previous reports suggested that these common missense variants were likely to act through dominant-negative or gain-of-function effects manner. It is still uncertain whether the intragenic deletion or duplication in PACS1 will be disease-causing. By using whole-exome sequencing, we first identified a novel heterozygous multi-exon deletion covering exons 12–24 in PACS1 (NM_018026) in four individuals (two brothers and their father and grandfather) in a three-generation family. The younger brother was referred to our center prenatally and was evaluated before and after the birth. Unlike SHMS, no typical dysmorphic facial features, intellectual problems, and structural brain anomalies were observed among these four individuals. The brothers showed a mild hypermyotonia of their extremities at the age of 3 months old and recovered over time. Mild speech and cognitive delay were also noticed in the two brothers at the age of 13 and 27 months old, respectively. However, their father and grandfather showed normal language and cognitive competence. This study might supplement the spectrum of PACS1-NDD and demonstrates that the loss of function variation in PACS1 displays no contributions to the typical SHMS which is caused by the recurrent c.607C > T (p.Arg203Trp) variant.

Teaching NeuroImage: Dorsal Medullary Lesions in Juvenile-Onset Alexander Disease.

A 6-year-old boy presented with dysphagia, vomiting, and weight loss. Early developmental milestones were notable for mild gross motor and speech delay. Hypotonia was present on examination. Brain MRI revealed bilateral enhancing dorsal medullary lesions (figure, contrast not shown). The differential diagnosis included a leukodystrophy or mitochondrial disease. Alexander disease was confirmed genetically (de novo variant in GFAP -targeted testing: p.Arg-376-Gly). Typical features also include hypernasal speech with subsequent motor difficulties and autonomic dysfunction over time.2 GFAP sequencing should be considered in patients with unilateral or bilateral dorsal medullary lesions with localizing symptoms (e.g., vomiting and dysphagia).

Hearing and Neurodevelopmental Outcomes of Young Infants with Parechovirus-A and Enterovirus Meningitis: Cohort Study in Singapore Children and Literature Review

Abstract Parechovirus-A (PeV-A) and Enterovirus (EV) commonly cause childhood aseptic meningitis. Bacterial meningitis in children has been associated with devastating long-term sequelae. However, developmental outcomes are unclear in Parechovirus meningitis. This study aims to review the clinical findings and developmental outcomes of infants with PeV-A and EV meningitis. We performed a retrospective study of infants aged 90 days or younger being admitted to our hospital with PeV-A meningitis between November 2015 and July 2017, with positive cerebrospinal fluid (CSF) PeV-A PCR and negative blood and CSF bacterial cultures. Hearing and neurodevelopmental outcomes were compared with a previous cohort of infants aged 90 days or younger with EV meningitis admitted from January 2015 to December 2015. A total of 161 infants were included in our study, of which 68 infants (42.2%) had PeV-A meningitis and 93 infants (57.8%) had EV meningitis. We assessed their developmental outcome at 6 months, 1 year, and 2 years post-meningitis. At 2 years post-meningitis, three infants with PeV-A meningitis had developmental delay (5.5%), whereas none with EV meningitis had developmental delay. One patient had speech delay and autism spectrum disorder, while two had mild speech delay. When compared with our cohort of EV meningitis ≤90 days old, children with PeV-A meningitis ≤90 days old were more likely to have developmental delay 2 years post-meningitis (odds ratio 2.4, 95% confidence interval 2.0–3.0, p = 0.043). None of the patients with PeV-A or EV meningitis had sensorineural hearing loss or neurological sequelae, such as cortical blindness, oropharyngeal dysphagia, hydrocephalus, epilepsy, or cerebral palsy. Infants with PeV-A meningitis had a significant risk of developmental delay 2 years post-meningitis compared with those with EV meningitis. It is important to follow-up the developmental milestones of infants diagnosed with PeV-A meningitis for at least 2 years; and when they develop developmental delay, to ensure that they receive appropriate intervention.

Sotos syndrome with a novel mutation in the NSD1 gene associated with congenital hypothyroidism

Childhood overgrowth syndromes are relatively rare. A generalized overgrowth syndrome should be suspected when tall stature and macrocephaly are present, after ruling out nutritional excess and endocrinopathies. Sotos syndrome is a well-described overgrowth syndrome due to haploinsufficiency of the NSD1 gene. We present a case of an infant with permanent congenital hypothyroidism, who had tall stature and macrocephaly by 7 months of age. He was noted to have typical facial features, mild gross motor and speech delay, and scoliosis by 13 months of age. Gene sequencing revealed a heterozygous novel c6076_6087del12: p.Asn2026_Thr2029del variant in exon 20 of the NSD1 gene, pathogenic for Sotos syndrome. Congenital hypothyroidism with Sotos syndrome has been infrequently reported and may expand the spectrum of disease characteristics. Early diagnosis of overgrowth syndromes is important for developmental follow up and multidisciplinary care coordination.

A new 1p36.13-1p36.12 microdeletion syndrome characterized by learning disability, behavioral abnormalities, and ptosis.

Two 1p36 contiguous gene deletion syndromes are known so far: the terminal 1p36 deletion syndrome and a 1p36 deletion syndrome with a critical region located more proximal at 1p36.23-1p36.22. We present even more proximally located overlapping deletions from seven individuals, with the smallest region of overlap comprising 1 Mb at 1p36.13-1p36.12 (chr1:19077793-20081292 (GRCh37/hg19)) defining a new contiguous gene deletion syndrome. The characteristic features of this new syndrome are learning disability or mild intellectual disability, speech delay, behavioral abnormalities, and ptosis. The genes UBR4 and CAPZB are considered the most likely candidate genes for the features of this new syndrome.

A novel 14q13.1\u201321.1 deletion identified by CNV-Seq in a patient with brain-lung-thyroid syndrome, tooth agenesis and immunodeficiency

BackgroundChromosome 14q11-q22 deletion syndrome (OMIM 613457) is a rare genomic disorder. The phenotype heterogeneity depends on the deletion size, breakpoints and genes deleted. Critical genes like FOXG1, NKX2–1, PAX9 were identified.Case presentationWe performed whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) for a patient with mild speech and motor developmental delay, short stature, recurrent pulmonary infections, tooth agenesis and triad of brain-lung-thyroid syndrome. By using CNV-seq, we identified a 3.1 Mb de novo interstitial deletion of the 14q13.2q21.1 region encompassing 17 OMIM genes including NKX2–1, PAX9 and NFKBIA. Our patient’s phenotype is consistent with other published 14q13 deletion patients.ConclusionOur results showed the combination of WES and CNV-seq is an effective diagnostic strategy for patients with genetic or genomic disorders. After reviewing published patients, we also proposed a new critical region for 14q13 deletion syndrome with is a more benign disorder compared to 14q11-q22 deletion syndrome.

First Replication of the Involvement of OTUD6B in Intellectual Disability Syndrome With Seizures and Dysmorphic Features.

Biallelic mutations in the ovarian tumor domain-containing 6B (OTUD6B) gene, coding for a deubiquitinating enzyme, were recently described to cause an intellectual disability syndrome characterized by seizures and dysmorphic features in six families worldwide. We here report on a 6-year-old Italian girl, presenting mild intellectual disability, speech and motor delay, and recurrent seizures, who came to our attention after being screened for genes responsible for Rubinstein–Taybi syndrome, Kabuki syndrome, and epilepsy. We hence submitted the proband’s DNA to whole-exome sequencing, disclosing two candidate heterozygous splicing mutations in the OTUD6B gene: c.324+1G>C and c.405+1G>A. Both variants are reported in the GnomAD database with a frequency lower than the 10−5 and affect the donor splicing site, of exons 2 and 3, respectively. Sanger sequencing confirmed the segregation of the variants in the family, showing that both parents are carriers of one mutation. RT-PCR experiments demonstrated that both variants affect OTUD6B splicing and lead to the production of aberrant transcripts, the major ones being, in both cases, the skipping of the upstream exon. Quantitative analysis performed by competitive-fluorescent RT-PCR on the patient RNA showed that the proband presents less than 1% of wild-type transcripts, further strengthening the causative role of these variants. This represents the first replication of the involvement of the OTUD6B gene in this syndrome and points to the appropriateness of screening OTUD6B in suspected Rubinstein–Taybi syndrome patients with negative results after the screening of the major genes.

Repolarisation anomalies and rhabdomyolysis

Acute rhabdomyolysis is a rare but potentially severe disease in childhood. Inherited metabolic disorders have to be searched for. Significant repolarisation abnormalities have been described in patients with acute rhabdomyolysis and TANGO2 mutation involved in the Golgi apparatus. Between 12/2013 and 01/2017, 4 children (mean age 3,5 years at first crisis) presented in our department with 1 to 3 acute severe rhabdomyolysis crises (CPK > 10,000 UI/L) associated with significant ECG anomalies. All 4 had neurodevelopmental delay (from mild speech delay to spastic tetraparesia, with microcephaly). Rhabdomyolysis occurred after acute viral illnesses or unusual fasting and were associated with neurological deterioration. Cardiac anomalies included significant lengthening of QT and QTc interval in all 4, concomitant bradycardia and life-threatening “torsades de pointe” in patient 1, left bundle branch bloc in patient 3 and ventricular arrhythmia and cardiac arrest in patient 4 ( Fig. 1 ). ECG anomalies were maximal around 10 days after the beginning of crisis and slightly delayed from the peak CPK level. Ventricular dysfunction was associated in patient 2 (mild) and in patient 3 (severe requiring inotrope support). Cardiac anomalies regressed completely in all between the rhabdomyolysis crises. Patient 1 died while admitted for her 3rd rhabdomyolysis crisis, with severe neurological worsening, prolonged QT but no ventricular arrhythmia. TANGO2 mutation was confirmed in patient 1, suspected but not yet confirmed for the 3 others. Ventricular conduction and function have to be explored in children with acute rhabdomyolysis in the setting of neurodevelopmental delay. TANGO2 mutations may be responsible. The cardiac disorders are rapidly progressive, potentially life-threatening but reversible. The mechanism and treatment are poorly defined.

P.294 - An unclassified congenital myopathy diagnosed as Snyder Robinson syndrome identified through the deciphering developmental disorders study

Snyder Robinson syndrome (SRS) (OMIM #309583) is a rare X-linked intellectual disability syndrome characterised by thin habitus, reduced muscle mass, osteoporosis, kyphoscoliosis, facial asymmetry and intellectual disability. The causative gene is the spermine synthase gene (SMS) located on the X chromosome. Boys with SRS have previously been shown to have a decreased spermine to spermidine ratio. Spermine is a polyamine and its reduction is thought to be responsible for the phenotypic effects associated with SRS. Polyamines have essential roles in cell physiology including gene expression, nucleic acid and protein synthesis and protection from oxidative damage. Less than twenty clinical cases of individuals with SRS have been reported previously in the literature all with novel or familial mutations identified. Boys with SRS have a spectrum of severity with inter-familial variability suggesting some genotype phenotype correlation. We report a new case of Snyder-Robinson Syndrome identified through the Deciphering Developmental Disorders (DDD) study with a missense variant (c.335C>T, P112L) in the SMS gene. This variant has been previously studied, but clinical details are not available. Our patient presented at 6 weeks of age with hypotonia, plagiocephaly and facial asymmetry. At 4 years had myopathic face, high arched palate, marked scoliosis, had an accessory nipple, wide-based gait, Gower's negative and flat feet. At 10 years of age he has a severe thoracic scoliosis, has had femoral fractures, focal seizures, and has mild developmental and speech delay. Standard neurological investigations (EEG abnormal, normal NCS, MRI brain and spine)were done. He has had two muscle biopsies with findings suggestive of congenital myopathy or mitochondrial cytopathy. SRS is likely to be underdiagnosed in the neuromuscular cohort. Next generation sequencing studies are anticipated to identify new cases.

Does the ex utero intrapartum treatment to extracorporeal membrane oxygenation procedure change morbidity outcomes for high-risk congenital diaphragmatic hernia survivors?

PurposeIn high-risk congenital diaphragmatic hernia (CDH), significant barotrauma or death can occur before extracorporeal membrane oxygenation (ECMO) can be initiated. We previously examined ex utero intrapartum treatment (EXIT)-to-ECMO in our most severe CDH patients, but demonstrated no survival advantage. We now report morbidity outcomes in survivors of this high-risk cohort to determine whether EXIT-to-ECMO conferred any benefit. MethodsAll CDH survivors with <15% predicted lung volume (PPLV) from September 1999 to December 2010 were included. We recorded prenatal imaging, defect size, and pulmonary, nutritional, cardiac, and neurodevelopmental outcomes. ResultsSeventeen survivors (8 EXIT-to-ECMO, 9 non-EXIT) had an average PPLV of 11.7%. Eight of 9 non-EXIT received ECMO within 2days. There were no significant defect size differences between groups, mostly left-sided (13/17) and type D (12/17). Average follow-up was 6.7years (0–13years). There were no statistically significant differences in outcomes, including supplemental oxygen, diuretics, gastrostomy, weight-for-age Z scores, fundoplication, pulmonary hypertension, stroke or intracranial hemorrhage rate, CDH recurrence, and reoperation. No survivor in our cohort was neurologically devastated. All had mild motor and/or speech delay, which improved in most. ConclusionsIn this pilot series of severe CDH survivors, EXIT-to-ECMO confers neither significant survival nor long-term morbidity benefit. Level of evidenceLevel III treatment study.

Auto-immune anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis: three case reports

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently identified auto-immune disorder characterised by severe memory deficit, a decreased level of consciousness, seizures, autonomic dysfunction and movement disorders. Three girls with the disorder are reported; they were aged 4 years, 5 years and 10 months. The 10-month-old infant who is one of the youngest patients reported with anti-NMDAR encephalitis worldwide, had MRI features suggestive of herpes simplex encephalitis (known to trigger anti-NMDAR encephalitis), but CSF PCR for herpes simplex was negative. All the patients presented with seizures, behavioural change, regression of speech, dystonia and choreo-athetosis. Anti-NMDAR antibodies were detected in all patients’ sera and cerebrospinal fluid (CSF). Intravenous immunoglobulin, corticosteroids and rituximab were administered at different intervals. Cases 1 and 2 made a full recovery, but case 3 has mild motor and speech delay. Patients who present with encephalopathy, seizures and movement disorders should be tested for anti-NMDAR antibodies in serum and CSF in addition to being screened for herpes simplex encephalitis.