Global developmental delay (GDD) and intellectual disability (ID) are relatively common neurodevelopmental disorders that significantly impact affected children, their families, and society. The etiology of GDD/ID is notably diverse, encompassing both genetic and acquired factors. Although the precise cause of most GDD/ID cases remains unclear, an estimated half of all cases can be attributed to genetic factors. Thus, a detailed medical history and comprehensive physical examination remain pivotal for guiding diagnostic investigations into the underlying causes of GDD/ID. Advancements in genetic testing have supplanted traditional methods such as karyotyping and fluorescence in situ hybridization with chromosomal micro arrays, which are now the primary genetic tests for children with idiopathic GDD/ID. Moreover, the evaluation of Fragile X and Rett syndrome should be an integral component of initial diagnostic assessments. In recent years, whole-exome sequencing and whole-genome sequ-encing have emerged as important diagnostic tools for evaluating children with GDD/ID and have substantially enhanced the diagnostic yield rates. Gene therapy has emerged as a promising avenue and is poised to become a cornerstone in addressing various genetic developmental and epilepsy disorders. Early intervention facilitated by a proficient multidisciplinary team can markedly enhance the prognosis and outcomes of GDD/ID, particularly when parents or caregivers are actively engaged in the interventional process. This review discusses risk factors and common underlying causes, explores recent evidence and recommendations for genetic evaluation, and offers management strategies for children with GDD/ID.

Global developmental delay (GDD) and intellectual disability (ID) are relatively common neurodevelopmental disorders that significantly impact affected children, their families, and society. The etiology of GDD/ID is notably diverse, encompassing both genetic and acquired factors. Although the precise cause of most GDD/ID cases remains unclear, an estimated half of all cases can be attributed to genetic factors. Thus, a detailed medical history and comprehensive physical examination remain pivotal for guiding diagnostic investigations into the underlying causes of GDD/ID. Advancements in genetic testing have supplanted traditional methods such as karyotyping and fluorescence in situ hybridization with chromosomal micro arrays, which are now the primary genetic tests for children with idiopathic GDD/ID. Moreover, the evaluation of Fragile X and Rett syndrome should be an integral component of initial diagnostic assessments. In recent years, whole-exome sequencing and whole-genome sequ-encing have emerged as important diagnostic tools for evaluating children with GDD/ID and have substantially enhanced the diagnostic yield rates. Gene therapy has emerged as a promising avenue and is poised to become a cornerstone in addressing various genetic developmental and epilepsy disorders. Early intervention facilitated by a proficient multidisciplinary team can markedly enhance the prognosis and outcomes of GDD/ID, particularly when parents or caregivers are actively engaged in the interventional process. This review discusses risk factors and common underlying causes, explores recent evidence and recommendations for genetic evaluation, and offers management strategies for children with GDD/ID.

Global developmental delay (GDD) and intellectual disability (ID) are relatively common neurodevelopmental disorders that significantly impact affected children, their families, and society. The etiology of GDD/ID is notably diverse, encompassing both genetic and acquired factors. Although the precise cause of most GDD/ID cases remains unclear, an estimated half of all cases can be attributed to genetic factors. Thus, a detailed medical history and comprehensive physical examination remain pivotal for guiding diagnostic investigations into the underlying causes of GDD/ID. Advancements in genetic testing have supplanted traditional methods such as karyotyping and fluorescence in situ hybridization with chromosomal micro arrays, which are now the primary genetic tests for children with idiopathic GDD/ID. Moreover, the evaluation of Fragile X and Rett syndrome should be an integral component of initial diagnostic assessments. In recent years, whole-exome sequencing and whole-genome sequ-encing have emerged as important diagnostic tools for evaluating children with GDD/ID and have substantially enhanced the diagnostic yield rates. Gene therapy has emerged as a promising avenue and is poised to become a cornerstone in addressing various genetic developmental and epilepsy disorders. Early intervention facilitated by a proficient multidisciplinary team can markedly enhance the prognosis and outcomes of GDD/ID, particularly when parents or caregivers are actively engaged in the interventional process. This review discusses risk factors and common underlying causes, explores recent evidence and recommendations for genetic evaluation, and offers management strategies for children with GDD/ID.

Global developmental delay (GDD) and intellectual disability (ID) are relatively common neurodevelopmental disorders that significantly impact affected children, their families, and society. The etiology of GDD/ID is notably diverse, encompassing both genetic and acquired factors. Although the precise cause of most GDD/ID cases remains unclear, an estimated half of all cases can be attributed to genetic factors. Thus, a detailed medical history and comprehensive physical examination remain pivotal for guiding diagnostic investigations into the underlying causes of GDD/ID. Advancements in genetic testing have supplanted traditional methods such as karyotyping and fluorescence in situ hybridization with chromosomal micro arrays, which are now the primary genetic tests for children with idiopathic GDD/ID. Moreover, the evaluation of Fragile X and Rett syndrome should be an integral component of initial diagnostic assessments. In recent years, whole-exome sequencing and whole-genome sequ-encing have emerged as important diagnostic tools for evaluating children with GDD/ID and have substantially enhanced the diagnostic yield rates. Gene therapy has emerged as a promising avenue and is poised to become a cornerstone in addressing various genetic developmental and epilepsy disorders. Early intervention facilitated by a proficient multidisciplinary team can markedly enhance the prognosis and outcomes of GDD/ID, particularly when parents or caregivers are actively engaged in the interventional process. This review discusses risk factors and common underlying causes, explores recent evidence and recommendations for genetic evaluation, and offers management strategies for children with GDD/ID.

Midazolam is generally effective and safe to be widely used in the management of seizures, procedural sedation, and anxiolytic. However, paradoxical reactions, though rare, present clinical challenges. Flumazenil is the preferred option for reversing the reactions. Additionally, ketamine, physostigmine, and haloperidol have been successfully used to counteract the adverse effects (AEs). Herein, we report an 11-year-old girl with epilepsy who was brought to the emergency department with a breakthrough seizure. Approximately 10 minutes after a midazolam administration, she developed increased agitation, confusion, uncontrollable crying, and excessive random movements. Despite receiving 4 doses of flumazenil, no improvement was observed. However, the AEs ceased following the administration of ketamine. This report may increase awareness of the uncommon AEs and equip clinicians to effectively handle such occurrences.

Midazolam is generally effective and safe to be widely used in the management of seizures, procedural sedation, and anxiolytic. However, paradoxical reactions, though rare, present clinical challenges. Flumazenil is the preferred option for reversing the reactions. Additionally, ketamine, physostigmine, and haloperidol have been successfully used to counteract the adverse effects (AEs). Herein, we report an 11-year-old girl with epilepsy who was brought to the emergency department with a breakthrough seizure. Approximately 10 minutes after a midazolam administration, she developed increased agitation, confusion, uncontrollable crying, and excessive random movements. Despite receiving 4 doses of flumazenil, no improvement was observed. However, the AEs ceased following the administration of ketamine. This report may increase awareness of the uncommon AEs and equip clinicians to effectively handle such occurrences.

Midazolam is generally effective and safe to be widely used in the management of seizures, procedural sedation, and anxiolytic. However, paradoxical reactions, though rare, present clinical challenges. Flumazenil is the preferred option for reversing the reactions. Additionally, ketamine, physostigmine, and haloperidol have been successfully used to counteract the adverse effects (AEs). Herein, we report an 11-year-old girl with epilepsy who was brought to the emergency department with a breakthrough seizure. Approximately 10 minutes after a midazolam administration, she developed increased agitation, confusion, uncontrollable crying, and excessive random movements. Despite receiving 4 doses of flumazenil, no improvement was observed. However, the AEs ceased following the administration of ketamine. This report may increase awareness of the uncommon AEs and equip clinicians to effectively handle such occurrences.

Midazolam is generally effective and safe to be widely used in the management of seizures, procedural sedation, and anxiolytic. However, paradoxical reactions, though rare, present clinical challenges. Flumazenil is the preferred option for reversing the reactions. Additionally, ketamine, physostigmine, and haloperidol have been successfully used to counteract the adverse effects (AEs). Herein, we report an 11-year-old girl with epilepsy who was brought to the emergency department with a breakthrough seizure. Approximately 10 minutes after a midazolam administration, she developed increased agitation, confusion, uncontrollable crying, and excessive random movements. Despite receiving 4 doses of flumazenil, no improvement was observed. However, the AEs ceased following the administration of ketamine. This report may increase awareness of the uncommon AEs and equip clinicians to effectively handle such occurrences.

Metoclopramide and domperidone are dopamine antagonists that can cause an acute dystonic reaction. Metoclopramide is a rare but major contributor to serotonin syndrome, particularly when used with other serotonergic agents. Serotonin syndrome is a rare, potentially life-threatening adverse reaction characterized by a triad of altered mental status, autonomic dysfunction, and neuromuscular hyperactivity that typically results from exposure to serotonergic agents. Herein, we report a previously healthy 9-year-old girl who was brought to the emergency department with an alteration in the level of conscious and involuntary repetitive movements after approximately 24 hours of receiving a therapeutic dose of metoclopramide and domperidone. Physical examination showed tachycardia, hyperthermia, and a Glasgow Coma Scale score of 11, as well as mydriasis and hyperreflexia. In addition to resolving the symptoms after administering midazolam and diphenhydramine, the diagnosis of serotonin syndrome was made based on the classical symptoms and signs, which met the Hunter criteria. This case indicates the need for clinical awareness of the life-threatening syndrome and caution with medications having potential interactions with metoclopramide.