History Of Developmental Delay Research Articles

Clinical phenotypes of individuals with Chung-Jansen syndrome across age groups.

Pathogenic variants in pleckstrin homology domain interacting protein (PHIP) are associated with Chung-Jansen syndrome characterized by developmental delay, intellectual disability, behavioral challenges, hypotonia, obesity, and dysmorphic features. We report phenotypes and genotypes of 47 individuals with likely pathogenic/pathogenic PHIP variants. Variants were de novo in 61.7%, unknown inheritance in 29.8%, and inherited in 8.5%. The median age of the individuals was 10.9 years, approximately equally divided by sex. Individuals in this cohort frequently had a history of developmental delay (85.1%), attention-deficit/hyperactivity disorder (51.1%), anxiety (46.8%), depression (27.7%), and sleep difficulties (42.6%). Depression was significantly higher in the older age group (>12 years old). Most individuals had moderately low adaptive functioning based on the Vineland-3 (mean = 76.8, standard deviation = 12.0). Overall, 55.8% of individuals were obese/overweight. The percentage of obese individuals was greater in the older age group (>12 years old) and evolves over time. Other common symptoms were hypotonia (78.7%), constipation (48.9%), visual problems (66%), and cryptorchidism (39.1% of males). Our findings provide additional natural history data for Chung-Jansen syndrome and provide opportunities for early intervention of healthy eating habits and awareness of developing mood and behavioral challenges over the life course.

THU168 PRMT7 Gene Mutation—A Rare Genetic Syndrome With Novel Endocrine Associations

Abstract Disclosure: K. Nutakki: None. S. Nalla: None. P. Deb: None. A. Vulpala: None. Background: Causes of short stature in children include pathologic causes (genetic diseases, underlying systemic disease, or growth hormone deficiency) and non-pathological variants such as familial and constitutional short stature. Genetic causes include Turner’s syndrome, SHOX mutations, Noonan’s syndrome and Silver- Russel syndrome besides others. Homozygous/compound heterozygous mutations in Protein Arginine Methyltransferase 7 (PRMT7) can result in Short Stature, Brachydactyly, Intellectual Developmental Disability and Seizures syndrome (SBIDDS) . Here, we report a child with SBIDDS syndrome who has associated endocrine manifestations of growth hormone deficiency and primary hypothyroidism. Case report: A 9-year-old male child, twin A of dichorionic diamniotic gestation, presented to the Endocrine OPD with short stature. There was a history of developmental delay, seizure disorder and mild intellectual deficit. Excessive weight gain was observed since 4 years of age. On examination, he was short with abdominal obesity, brachydactyly, simian crease and macroglossia. Height was below 3rd centile and weight at the 97th percentile. SMR was pre-pubertal. Investigations confirmed primary hypothyroidism.GH deficiency (peak GH after clonidine stimulation was less than 4 microgram/L) and reduced IGF-I levels were also found. Twin B was noted to have a normal height percentile. In both, skeletal maturation was consistent with chronological age. Twin A was treated with rGH and levothyroxine and responded well to rGH treatment. Whole exome sequencing revealed homozygosity for PRMT7 mutation in twin A with both parents heterozygous for the same gene mutation. His twin sibling, twin B was also found to be homozygous for the mutation, but he did not display any characteristics of the syndrome. Discussion: To the best of our knowledge, this is only the second reported case of SBIDDS syndrome (PRMT7 mutation) with documented growth hormone deficiency and only case with documented primary hypothyroidism. Height gain observed over the period of rGH treatment is suggestive of a possible role of GH/IGF-I axis alterations as contributors of growth impairment in these children. PRMT7 encodes for an arginine methyltransferase, involved in several biological processes, such as DNA transcription and repairing, RNA splicing, cell differentiation. We would like to propose that children with SBIDDS syndrome may be tested for GH deficiency as part of their overall assessment. Likewise, it should be further explored if PRMT7 gene mutation testing should be recommended in a child presenting with short stature and one or more manifestations of SBIDDS syndrome. Presentation: Thursday, June 15, 2023

Novel RAB39B variant associated intellectual disability and levodopa-responsive young-onset parkinsonism

We report a 37-year-old Caucasian male with history of developmental delay, childhood onset Intellectual Disability (ID) and attention deficit hyperactivity disorder (ADHD) who presented at the age of 34 with tremor-dominant parkinsonism. Next Generation Sequencing (NGS) revealed pathogenic hemizygous sequence variant, c.200G > T, in the RAB39B gene. This report expands the number of described individuals with young onset PD associated with RAB39B mutation.

Relationship Between Pericallosal Lipoma and Neuropsychiatric Symptoms: A Case Report.

Intracranial lipomas are extremely rare fat-containing lesions that occur due to the abnormal differentiation of embryonic meninges. Interhemispheric lipomas that are closely related to the corpus callosum are also referred to as pericallosal lipomas and are the most common subtype. Pericallosal lipomas are associated with varying degrees of dysgenesis of the corpus callosum and therefore have a broad clinical presentation. Herein, we describe a case of a 15-year-old man who presented with a history of developmental delay and psychiatric symptoms and was incidentally found to have a pericallosal lipoma on magnetic resonance imaging, prompting clinical correlation.

Hyaline protoplasmic astrocytopathy in epilepsy.

Hyaline protoplasmic astrocytopathy (HPA) describes a rare histologic finding of eosinophilic, hyaline cytoplasmic inclusions in astrocytes, predominantly in the cerebral cortex. It has mainly been observed in children and adults with a history of developmental delay and epilepsy, frequently with focal cortical dysplasia (FCD), but the nature and significance of these inclusions are unclear. In this study, we review the clinical and pathologic features of HPA and characterize the inclusions and brain tissue in which they are seen in surgical resection specimens from five patients with intractable epilepsy and HPA compared to five patients with intractable epilepsy without HPA using immunohistochemistry for filamin A, previously shown to label these inclusions, and a variety of astrocytic markers including aldehyde dehydrogenase 1 family member L1 (ALDH1L1), SRY-Box Transcription Factor 9 (SOX9), and glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) proteins. The inclusions were positive for ALDH1L1 with increased ALDH1L1 expression in areas of gliosis. SOX9 was also positive in the inclusions, although to a lesser intensity than the astrocyte nuclei. Filamin A labeled the inclusions but also labeled reactive astrocytes in a subset of patients. The immunoreactivity of the inclusions for various astrocytic markers and filamin A as well as the positivity of filamin A in reactive astrocytes raise the possibility that these astrocytic inclusions may be the result of an uncommon reactive or degenerative phenomenon.

A Modern Artillery to put off the Electric Storm of the Brain–A case report of aborting seizure with brivaracetam 2-minute intravenous bolus in a patient with a compromised airway. (P8-7.004)

<h3>Objective:</h3> A case report of successful seizure treatment using bolus administration of intravenous brivaracetam over 2 minutes in a patient with compromised airway. <h3>Background:</h3> As time is brain, it is paramount to rapidly treat seizures and status epilepticus to avoid permanent neuronal injuries. Benzodiazepines are the recommended first-line antiepileptic medications, but with initial and repetitive dosing, airway compromise can occur even before seizure resolution. Alternative fast-acting antiepileptics that can minimize this effect could lead to better outcomes and decreased ICU stays. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> Our patient is a 47-year-old male with a history of developmental delay and chronic ventriculomegaly was successfully extubated after external ventricular drain weaning. While his mentation improved, he had ongoing difficulties clearing secretions requiring a heated high-flow nasal cannula and repeated nebulizer treatments. The following day, the patient acutely had a seizure, manifesting as obtundation, whole body rigidity, and left lateral forced gaze deviation. Given ongoing respiration issues, lorazepam was held, and he was given a 2-minute bolus of intravenous brivaracetam 100mg instead. Post administration, patient’s mentation improved with the resolution of the gaze deviation. Continuous video electroencephalogram did not show any electrographic seizures. Patient was continued on brivaracetam 100 mg twice daily. <h3>Conclusions:</h3> Brivaracetam with high lipophilicity of 1.04 and T-max of less than 5 minutes can be given intravenously as a rapid 2-minute bolus. While there are no high-quality studies substantiating the efficacy of brivaracetam as a first-line medication, its pharmacokinetic/pharmacodynamic properties could make it a reasonable alternative to benzodiazepines as the first-line anti seizures medication, especially in pre-existing tenuous airways to avoid further compromise and reduce ICU and hospital length of stay. The benefits of its fast onset of action and efficacy may mitigate the major barriers of ready accessibility and cost. <b>Disclosure:</b> Dr. Tang has nothing to disclose. Prathyankara Premkumar has nothing to disclose.

424 Clinical Translational Approach to Targeted Therapy in SLC6A1-related Neurodevelopmental Disorder

OBJECTIVES/GOALS: SLC6A1-Related Neurodevelopmental Disorder (SLC6A1-NDD) is a leading genetic cause of epilepsy and autism. Haploinsufficiency of SLC6A1 leads to reduced uptake of GABA from the synaptic cleft, and increased extracellular GABA in mice. It is a candidate for gene transfer therapy, but translational read outs are needed. EEG is a promising biomarker. METHODS/STUDY POPULATION: The SLC6A1-NDD program includes a specialty clinic and prospective cohort study run in parallel with pre-clinical gene therapy development. Characterization and pre-clinical testing of a homozygous knock-out, heterozygous knock-out, and two humanized knock-in models are on-going, including EEG analyses before and after treatment. Patients with a confirmed diagnosis of SLC6A1-NDD are seen annually in a specialty clinic and a subset participate in the cohort study which collects standardized questionnaires, EEGs, and MR Spectroscopy to measure glutamate and GABA. Gene Therapy Program investigators meet weekly to discuss progress on pre-clinical and clinical trial readiness on SLC6A1-NDD and to align efforts on translational read outs, including EEG, in both humans and the pre-clinical models. RESULTS/ANTICIPATED RESULTS: We have enrolled the full cohort of 20 participants in the prospective SLC6A1-NDD cohort study. Preliminary results have shown that all but 1 individual has a history of developmental delay, and 8 of the 24 individuals in our clinical cohort had at least one episode of developmental regression. Over 90% have epilepsy, and 17/20 in the cohort study have intermittent rhythmic delta activity on EEG. The full knock out mice have behavioral and learning deficits and abnormal electrical brain activity on telemetry, including bursts of spike trains, analogous to epileptiform activity seen in humans. Next steps include quantitative analysis of both mouse and human EEG to develop a translational brain-based biomarker. We plan to assess delta power and investigate genotype-phenotype correlations in mice and humans. DISCUSSION/SIGNIFICANCE: With targeted therapies in development for SLC6A1-NDD, translational biomarkers that demonstrate engagement with the brain are critical. With clinical heterogeneity in SLC6A1-NDD, biomarkers can objectively capture change. Collaborative translational projects may improve efficiency in rare disease research to facilitate early phase trials.

Outcomes of two different unbalanced segregations from a maternal t(4;10)(q33;p15.1) translocation

BackgroundUnbalanced translocations can cause developmental delay (DD), intellectual disability (ID), growth problems, dysmorphic features, and congenital anomalies. They may arise de novo or may be inherited from a parent carrying a balanced rearrangement. It is estimated that 1/500 people is a balanced translocation carrier. The outcomes of different chromosomal rearrangements have the potential to reveal the functional consequences of partial trisomy or partial monosomy and can help guide genetic counseling for balanced carriers, and other young patients diagnosed with similar imbalances.MethodsWe performed clinical phenotyping and cytogenetic analyses of two siblings with a history of developmental delay (DD), intellectual disability (ID) and dysmorphic features.ResultsThe proband, a 38-year-old female, has a history of short stature, dysmorphic features and aortic coarctation. She underwent chromosomal microarray analysis, which identified partial monosomy of 4q and partial trisomy of 10p. Her brother, a 37-year-old male, has a history of more severe DD, behavioral problems, dysmorphic features, and congenital anomalies. Subsequently, karyotype confirmed two different unbalanced translocations in the siblings: 46,XX,der(4)t(4;10)(q33;p15.1) and 46,XY,der(10)t(4;10)(q33;p15.1), respectively. These chromosomal rearrangements represent two possible outcomes from a parent who is a carrier for a balanced translocation 46,XX,t(4;10)(q33;p15.1).ConclusionTo our knowledge, this 4q and 10p translocation has not been described in literature. In this report we compare clinical features due to the composite effects of partial monosomy 4q with partial trisomy 10p and partial trisomy 4q with partial monosomy 10p. These findings speak to the relevance of old and new genomic testing, the viability of these segregation outcomes, and need for genetic counseling.

Risk factors for seizure recurrence after initial withdrawal of anti-seizure medications in children with epilepsy at Aga Khan University Hospital, Nairobi, Kenya.

We sought to determine risk factors associated with seizure recurrence following initial withdrawal of anti-seizure medications (ASM) among children with epilepsy. This was a retrospective observational study of children aged between 2 and 18years with a diagnosis of epilepsy who underwent withdrawal of anti-seizure medication following remission of seizures. All eligible medical records between January 2011 and December 2019 were included. Demographic, clinical, imaging and electroencephalography data of all eligible patients were analyzed against seizure remission within 24months after withdrawal of ASM, using appropriate parametric and non-parametric tests. A total of 49 records of children who underwent withdrawal of ASM out of a total of 613 patients on follow up during the same period were included. The median age at ASM withdrawal was 70months (IQR 52-112months) and 14 (28.6%) were female. Thirteen patients (26.5%) had seizure recurrence within 24months following withdrawal of ASM. Focal onset seizure type was associated with significant risk of seizure recurrence (OR 13.7; 95% CI 0.97, 193.54; P value=0.011). Age at epilepsy diagnosis, abnormal EEG at initiation of treatment and at the time of de-escalation, abnormal MRI findings, first or second degree relative with epilepsy, history of developmental delay, seizure burden, use of 2 or more ASMs and duration of seizure-freedom before de-escalation of ASM were not associated with increased risk of relapse. Focal onset seizure type is associated with increased with risk of seizure recurrence in this cohort.

Novel PGM3 mutation in two siblings with combined immunodeficiency and childhood bullous pemphigoid: a case report and review of the literature

BackgroundBullous pemphigoid is the most common autoimmune subepidermal blistering disorder with a low incidence in childhood. Combined immunodeficiencies (CIDs) are a group of monogenic inborn errors of immunity (IEIs) characterized by T- and B-cell dysfunction leading to recurrent infections, lymphoproliferation, predisposition to malignancy, and autoimmunity. Here, we report two Afghan siblings with a diagnosis of CID and extremely rare manifestation of diffuse bullous pemphigoid skin lesions.Case presentationThe older sibling (patient 1) was a 32-month-old male with facial dysmorphism, protracted diarrhea, failure to thrive, recurrent oral candidiasis, recurrent otitis media with tympanic membrane perforation, who had been previously diagnosed with CID. While he was under treatment with intravenous immunoglobulin (IVIg), he developed extensive blistering lesions, which were diagnosed as childhood bullous pemphigoid. Methylprednisolone and azathioprine were added to the regimen, which resulted in a remarkable improvement of the skin lesions and also the feeding condition. However,2 weeks later, he was re-admitted to the intensive care unit (ICU) and eventually died due to fulminant sepsis. Later, his 12-month-old sister (patient 2) with similar facial dysmorphism and a history of developmental delay, food allergy, recurrent oral candidiasis, and respiratory tract infections also developed blistering skin lesions. She was under treatment for occasional eczematous lesions, and had been receiving IVIg for 3 months due to low levels of immunoglobulins. Further immunologic workup showed an underlying CID and thus treatment with IVIg continued, gradually improving her clinical condition. The genetic study of both siblings revealed a novel homozygous mutation in exon 7 of the PGM3 gene, c.845 T > C (p.Val282Ala).ConclusionsDermatologic disorders may be the presenting sign in patients with CID and mutated PGM3. This case report further extends the spectrum of skin manifestations that could be observed in PGM3 deficiency and emphasizes the importance of considering CIDs during the assessment of skin disorders, particularly if they are extensive, recurrent, refractory to treatment, and/or associated with other signs of IEIs.

ODP472 Creation of the Anaplastic Care Team (ACT) protocol: Establishing a Benchmark for Timely Access to Care for Anaplastic Thyroid Cancer Patients

Abstract Introduction Novel Coronavirus 19 (COVID19) has been shown to involve multiple organs. Its reported effects on the endocrine system have been via subacute thyroiditis, functional hypopituitarism, and triggering type 1 diabetes with ketosis. We describe a case of COVID19 infection presenting as adrenal insufficiency. Case A 35-year-old female with a history of developmental delay, anxiety, and hypothyroidism presented to the emergency department (ED) from her group home with complaints of abdominal pain and 2-3 episodes of nausea and vomiting per day for one week. She denied any changes in bowel habits, chest pain, shortness of breath. On physical examination, there was mild diffuse abdominal tenderness without any skin hyperpigmentation. In the ED, her vitals showed blood pressure 99/56, heart rate 94, respiratory rate 23, saturating at 100% on room air. Laboratory tests were remarkable for hyponatremia (sodium 123), hypokalemia (potassium 1.9), hypochloremia (chloride 88), hypophosphatemia (phosphorus 2), metabolic acidosis with bicarbonate of 14. Her COVID19 test was positive. She was admitted to the intensive care unit as her blood pressure continued to drop to as low as 76/37. Potassium, phosphorus was replaced, and normal saline infusion was started at 75ml/hr with minimal improvement in blood pressure to 94/53 and sodium to 126 in 24 hours. Urine electrolytes showed sodium &amp;lt;15, making SIADH less likely. On day 3, we suspected adrenal insufficiency due to persistent hypotension. Results showed am cortisol of 1 and ACTH of 10. ACTH stimulation test was unable to be done. She was started on hydrocortisone which improved her blood pressure as well as electrolytes. CT abdomen showed no adrenal abnormality. She was able to be tapered off the steroids in 2 weeks. Conclusion COVID19 associated hypocortisolism presents both as primary and transient secondary adrenal insufficiency (via suppression of the hypothalamic-pituitary-adrenal axis, like in our case). Similar reversible hypocortisolism post-SARS infection was observed in 24 of 61 patients (39.3%) during the 2005 outbreak. Autopsy studies on patients with COVID19 showed adrenal necroptosis of the adrenal cortex. Although critical illness-related cortical insufficiency is not a new concept, the cortisol levels in COVID19 critically ill patients have been shown to be lower than non-COVID19 critically ill patients. Prompt addition of stress dose steroids can be lifesaving in critically ill COVID patients, especially when associated with resistant hypotension. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

THROMBOCYTOPENIA, HYPOGAMMAGLOBULINEMIA, AND POOR VACCINE RESPONSE IN A PATIENT WITH TAKENOUCHI-KOSAKI SYNDROME

<h3>Introduction</h3> Takenouchi-Kosaki Syndrome (TKS) is a rare congenital developmental disorder characterized by thrombocytopenia, facial abnormalities, and varied multisystemic anomalies including immunodeficiency. Heterozygous deficiency of CDC42, an intracellular signaling GTPase, has been found in all TKS patients described to date. The immunological phenotypes of TKS patients are heterogeneous: recurrent infections have been noted in some patient series but with variable penetrance. Herein we describe a case of TKS causing hypogammaglobulinemia, B-cell lymphopenia, and poor vaccine response. <h3>Case Description</h3> A fifteen-year-old girl with history of developmental delay, multiple congenital defects, and lymphedema was referred to the immunology clinic for evaluation of recurrent ear infections that began at 3 months of age requiring tympanostomy tube placement at 18 months. Her physical exam was notable for abnormal facies, scoliosis, strabismus, abnormal thumbs, and unilateral lymphedema. Her laboratory evaluation revealed macrothrombocytopenia, mild leukopenia with low T-cells and markedly low B-cells by flow cytometry, and notably low IgA (11.7, RR 69 – 309) and IgG (423, RR 613 – 1295). She had a poor response to a full course of PCV7 with PPSV23 booster (9 of 23 > 1.3). Whole exome sequencing identified a heterozygous p.Y64C mutation in CDC42 consistent with TKS. <h3>Discussion</h3> The Y64C mutation in CDC42 is a TKS Group I lesion causing ineffective intracellular signaling, resulting in <i>in vitro</i> defects including abnormal cellular proliferation and disruption of cell polarity. Actin remodeling disorders such as Wiskott-Aldrich Syndrome and TKS should be considered in patients with immunodeficiency and congenital thrombocytopenia.

Hypomelanosis of Ito: Neurocuteneous Syndrome

A 7-year-old girl, 2nd issue of non-consanguineous parents hailing from Rajshahi got attended to our outpatient department of Pediatrics with the complaints of white patches all over the body since early infancy, poor intelligence, and speech problems. There was history of developmental delay but no history of seizures or visual problems or hearing impairment. She also had dental abnormalities. Family history was not significant. For these she treated with several oral and local antibacterial, antifungal and corticostresoid medications, but no improvement. Examination revealed symmetrical hypopigmented patches involving the trunk and upper limbs, and were following Blaschko’s lines. Anthropometry and others examination were normal. The hearing assessment was normal. There were no ocular abnormalities but have delayed dentation with mal-alignment of teeth with carries. She have moderate level of intellectual disability (ID). Our diagnosis was hypomelanosis of Ito (HI); a rare type of neurocuteneous syndrome. Routine investigations were normal, CT scan of the brain showed mild cortical atrophy, EEG was normal. The parents were counseled about the recent level of intellectual functioning, asked to allow the child for learning self-help skills, and referred to a child development center, child psychologist, and speech therapist. Our patients were well and no complications were observed till writing this report. We like to share our experience of diagnosing and treating this very rare disease of HI. KYAMC Journal Vol. 13, No. 02, July 2022: 120-123

LB1020 Scurvy: A forgotten illness?

Scurvy is classically thought to be a historical disease rarely found in developed countries, thanks to increased awareness of the role of ascorbic acid in this disease. A non-verbal 19-year-old female with a history of developmental delay, G-tube (and by mouth intake), gumline bleeding, and poor dietary intake, presented with bilateral lower extremity non-palpable petechial, perifollicular eruptions. She denied any significant pain, itch, or irritation from the rash. Perifollicular petechiae and scattered corkscrew hairs were found on dermoscopy examination. A suspicion of Scurvy from her history and physical examination was confirmed by the serum levels of vitamin C <0.1 mg/dL. Although, the diagnosis is clinical, a histopathologic examination showed hyperkeratosis with irregular acanthosis of the epidermis and follicular spongiosis with erythrocyte extravasation adjacent to a hair follicle consistent with Scurvy. Scurvy is a well-documented disease caused due to a deficiency in Vitamin C, a known cofactor of enzymes involved in the synthesis of collagen, carnitine and catecholamines, and in gene expression and maintenance. Thorough dermascopic examination will reveal symptoms such as perifollicular petechiae and corkscrew hairs1 - some of the diagnostic clues to lack of functioning collagen, that occur with Scurvy. Other symptoms of collagen dysfunction include gingival bleeding, ecchymosis, epistaxis, and bone hemorrhage. In developed countries, patients with avoidant-restrictive food intake or those with renal imbalances are at risk of acquiring Scurvy. Therefore, it is important to keep Scurvy in the differentials in patients presenting with petechiae and perform a comprehensive physical exam, to avoid misdiagnosis. 1. Hirschmann, J.V. and G.J. Raugi, Adult scurvy. J Am Acad Dermatol, 1999. 41(6): p. 895-906; quiz 907-10. https://doi.org/ 10.1016/s0190-9622(99)70244-6.

MO036: Detection of copy number variations by single-nucleotide-polymorphism array in patients with end-stage renal disease of unknown etiology

Abstract BACKGROUND AND AIMS Establishing the genetic basis of renal disease is pivotal to improve diagnostic and treatment strategies. Pathogenic copy number variations (CNVs) caused by chromosomal imbalances contribute significantly to the pediatric renal disease burden, especially in children with congenital anomalies of the kidney and urinary tract (CAKUT). The role of CNVs in chronic kidney disease of unknown etiology (uCKD) is scarcely investigated, although this group comprises about 20% of adults with end-stage renal disease (ESRD). We screened for causal CNVs in a preliminary sample of patients with ESRD from unknown etiology. METHOD We recruited 94 patients registered with ESRD ≤age 50 from uCKD or hypertension from the Danish Nephrology Registry. Medical records and previous kidney biopsies were initially reviewed, and patients were excluded if a specific cause of kidney disease other than hypertension was identified (n = 35). We performed genome-wide single-nucleotide-polymorphism (SNP) array in 59 patients to identify copy number gains and losses. All CNVs were systematically evaluated as possible causes of kidney disease and broadly classified into three main categories: ‘Normal’, ‘Pathogenic’ or ‘Variant of uncertain significance.’ RESULTS The SNP array results were normal in 57 patients (96.6%). In the remaining two patients (3.4%), we detected pathogenic CNVs with incomplete penetrance in hot spot loci associated with CAKUT: One male patient with ESRD at age 18 was a heterozygous carrier of a 545 kb microdeletion on chromosome 16p11.2 (29.63 Mb to 30.18 Mb). He had left-side renal agenesis and a hypoplastic right kidney at presentation, but no history of developmental delay or dysmorphic features. The microdeletion was considered likely causal, because it included the CAKUT driver gene TBX6 similar to other heterozygous carriers of 16p11.2 microdeletions with isolated renal agenesis or dysplasia. A second patient with ESRD at age 49 had 3.66 Mb duplication on chromosome 1q21.1 (145.43 Mb to 149.09 Mb) in heterozygous form. The patient had no reported CAKUT or other features associated with CNVs in the 1q21.1 loci, and the duplication was therefore deemed unrelated to his renal disease. CONCLUSION Disease-causing CNVs are not frequent in this limited sample of patients with ESRD from unknown etiology. CNV analysis by SNP-array may be most effective in patients with uCKD combined with CAKUT features.

Supernumerary derivative 22 chromosome resulting from novel constitutional non-Robertsonian translocation: t(20;22)\u2014Case Report

BackgroundMaternal non-Robertsonian translocation-t(20;22)(q13;q11.2) between chromosomes 20 and 22resulting in an additional complex small supernumerary marker chromosome as derivative (22)inherited to the proband is not been reported yet.Case presentationA 4 years old boy with a history of developmental delay, low set ears, and facial dysmorphism was presented to the genetic clinic. Periauricular pit, downward slanting eyes, medially flared eyebrows, downturned mouth corners, and micrognathia were observed. He had congenital heart defect with atrial septal defect (ASD), ventricular septal defect (VSD), and central nervous system (CNS) anomalies with the gross cranium. Karyotype analysis, Fluorescent in-situ hybridization analysis (FISH), and Chromosomal microarray analysis (CMA) were used to determine the chromosomal origin and segmental composition of the derivative 22 chromosome. Karyotype and FISH analyses were performed to confirm the presence of a supernumerary chromosome, and Microarray analysis was performed to rule out copy number variations in the proband's 22q11.2q12 band point. The probands' karyotype revealed the inherited der(22)t(20;22)(q13;q11.2)dmat. Parental karyotype confirmed the mother as the carrier, with balanced non-Robertsonian translocation-46,XX,t(20;22)(q13;q11.2).ConclusionThe mother had a non-Robertsonian translocation t(20;22)(q13;q11.2) between chromosomes 20 and 22, which resulted in Emanuel syndrome in the proband. The most plausible explanation is 3:1 meiotic malsegregation, which results in the child inheriting derivative chromosome. The parental karyotype study aided in identifying the carrier of the supernumerary der(22), allowing future pregnancies with abnormal offspring to be avoided.

A case report on clinical feature, cause and outcome in male pediatric child with cerebral palsy with corpus callosum agenesis with mycosis

Introduction : The most prevalent developmental issue impacting children’s function is cerebral palsy. Brain damage or insult during pregnancy, perinatal, or postnatal periods causes a static, nonprogressive disease. The corpus callosum connects the left and right hemispheres of the brain and is one of the disorders that affect the agenesis of the corpus callosum. The corpus callosum is either absent or substantially absent in ACC. A disruption in brain cell migration during foetal development causes it. Mucormycosis is the third most frequent invasive fungal infection in children, according to recent studies, and its prevalence is increasing. Present complaints and Investigation : A 12-year-old male boy was presented to the hospital with oedema around his eyes, a fever that had been present for three days, respiratory distress, and altered sensorium. He had a history of developmental delay and cerebral palsy. Corpus callosal agenesis is visible on MRI and CT scans of the brain. The lesions have shifted the right orbital muscles. Right eye proptosis is evident. The main diagnosis, therapeutic intervention and outcomes : The doctor diagnosed a case of cerebral palsy with corpus callosal agenesis, retroorbital oedema, and mycosis after a physical examination and inquiry. Vancomycin, MgSO4, and other pharmacological treatments were administered intravenously. For four days, the patient was on CPAP. She received every treatment, but the prognosis was dismal. Her signs and symptoms of respiratory distress were decreased. Conclusion : The thickness of the mid-body of the corpus callosum correlates with the volume of cerebral white matter in children with cerebral palsy and developmental delay, regardless of gestational age or neuromotor outcome.

Case Report : Pregnancy Diet

Introduction : The most prevalent developmental issue impacting children’s function is cerebral palsy. Brain damage or insult during pregnancy, perinatal, or postnatal periods causes a static, nonprogressive disease. The corpus callosum connects the left and right hemispheres of the brain and is one of the disorders that affect the agenesis of the corpus callosum. The corpus callosum is either absent or substantially absent in ACC. A disruption in brain cell migration during foetal development causes it. Mucormycosis is the third most frequent invasive fungal infection in children, according to recent studies, and its prevalence is increasing. Present complaints and Investigation : A 12-year-old male boy was presented to the hospital with oedema around his eyes, a fever that had been present for three days, respiratory distress, and altered sensorium. He had a history of developmental delay and cerebral palsy. Corpus callosal agenesis is visible on MRI and CT scans of the brain. The lesions have shifted the right orbital muscles. Right eye proptosis is evident. The main diagnosis, therapeutic intervention and outcomes : The doctor diagnosed a case of cerebral palsy with corpus callosal agenesis, retroorbital oedema, and mycosis after a physical examination and inquiry. Vancomycin, MgSO4, and other pharmacological treatments were administered intravenously. For four days, the patient was on CPAP. She received every treatment, but the prognosis was dismal. Her signs and symptoms of respiratory distress were decreased. Conclusion : The thickness of the mid-body of the corpus callosum correlates with the volume of cerebral white matter in children with cerebral palsy and developmental delay, regardless of gestational age or neuromotor outcome.

S1857 Gastrointestinal Histoplasmosis in an Immunocompetent Adult in a Non-Endemic Region

Introduction: Histoplasma capsulatum is an endemic fungus and infection is rarely seen in the United States outside of the Ohio and Mississippi River regions. Disseminated infection is typically seen in immunocompromised patients and primary gastrointestinal involvement is rare. We report the case of an immunocompetent adult who was diagnosed with disseminated histoplasmosis with primarily gastrointestinal symptoms. Case description/methods: A 34-year-old male with history of developmental delay and prior seizures presented with seven months of intermittent bloody diarrhea, abdominal pain, fever and chills. He had a similar presentation previously at another hospital and underwent colonoscopy with evidence of multiple ulcers throughout the colon. He was empirically treated with antibiotics but re-presented due to persistent symptoms. Patient was intermittently febrile on admission. Exam showed diffuse abdominal tenderness to palpation. Labs were notable for Hgb 9.1 g/dL and, WBC 12.3 × 10^9 cells/L Stool calprotectin 1570 mcg/g. CT abdomen showed diffuse colonic thickening. Colonoscopy showed discontinuous scattered non-bleeding deep ulcers throughout the entire colon (Figure 1) which were biopsied. Pathology showed histiocytes with intracellular fungal elements. Even duodenal biopsies showed intracellular fungal elements though the duodenal mucosa appeared normal aside from some lymphoid aggregates on upper endoscopy. Urine histoplasma galactomannan antigen was positive. He had no evidence of pulmonary disease. Further history revealed that the patient had never traveled outside of California but did have some close contact with relatives from Minnesota prior to the onset of symptoms. Other infectious work-up including Aspergillus, HIV, CMV, Coccidiomycosis, Cryptococcus were all normal. He was initially treated with oral itraconazole with no improvement of his symptoms, however symptom resolved after initiating IV amphotericin. Genetic testing is pending for underlying immunodeficiency. Discussion: This unique case illustrates disseminated histoplasmosis with mainly gastrointestinal symptoms in a seemingly immunocompetent adult in a non-endemic area. The patient had diffuse small bowel and colonic involvement led to symptoms mimicking inflammatory bowel disease and he even had a markedly elevated calprotectin. Prior case series of disseminated histoplasmosis have reported 100% mortality when untreated. Endoscopic biopsies were crucial to help make the diagnosis and appropriate therapy.Figure 1.: Deep, non-bleeding ulcerations found in transverse colon on colonoscopy.Table 1.: EGD and colonoscopy biopsy results.

A Very Large Bowel

Question: A 60-year-old woman with a history of developmental delay and seizures was brought from a nursing home facility to the emergency department for evaluation of a change in mental status and hypoxemia. On examination, her temperature was 98.2 °F; heart rate, 78/min; blood pressure, 171/88 mm Hg; and respiratory rate, 20/min with oxygen saturation 97% on 3 L of oxygen. She was lethargic and only responded to painful stimuli. The abdomen was significantly distended but nontender with hypoactive bowel sounds.