Research

Jump to: Other

22 pages, 1571 KiB

Open AccessArticle

Qualitative Insights into Key Angelman Syndrome Motor Related Concepts Reported by Caregivers—A Thematic Analysis of Semi-Structured Interviews

by Miranda Rogers, Stéphane Motola, Yacine Bechichi, Céline Cluzeau, Tanguy Terray, Allyson Berent, Jennifer Panagoulias, Jessica Duis, Damien Eggenspieler and Laurent Servais

Children 2023, 10(9), 1462; https://doi.org/10.3390/children10091462 - 28 Aug 2023

Viewed by 1141

Abstract

Previous patient-centered concept models of Angelman syndrome (AS) are integral in developing our understanding of the symptoms and impact of this condition with a holistic perspective and have highlighted the importance of motor function. We aimed to develop the motor and movement aspects [...] Read more.

Previous patient-centered concept models of Angelman syndrome (AS) are integral in developing our understanding of the symptoms and impact of this condition with a holistic perspective and have highlighted the importance of motor function. We aimed to develop the motor and movement aspects of the concept models, to support research regarding motor-related digital outcomes aligned with patients’ and caregivers’ perspectives. We conducted a qualitative analysis of semi-structured interviews of 24 caregivers to explore AS motor-related features, factors influencing them and their impact on patients and caregivers.The most impacted motor features were gait, walking and stair-climbing. Half of caregivers ranked motor symptoms as one of the most burdensome symptoms of AS. Caregivers frequently reported physical therapy, motivation, medical management and age as factors influencing motor function in AS and reported that impaired motor function affected both patients and caregivers. Measures of lower-limb motor function were identified as relevant to monitor drug effectiveness in AS. Caregivers discussed expected benefits of a digital outcome and potential issues with wearable technology in the context of AS. We propose a new motor function patient-centered concept model, providing insights for the development of relevant, motor-related, digital outcomes in AS. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

► Show Figures

Figure 1

14 pages, 602 KiB

Open AccessArticle

The Diagnostic Process for Children with Autism Spectrum Disorder: A Preliminary Study of Jordanian Parents’ Perspectives

by Mizyed Hyassat, Ahmad Al-Makahleh, Zahraa Rahahleh and Nawaf Al-Zyoud

Children 2023, 10(8), 1394; https://doi.org/10.3390/children10081394 - 15 Aug 2023

Cited by 1 | Viewed by 1319

Abstract

Although extensive research has been conducted worldwide to investigate the diagnostic process of Autism Spectrum Disorder (ASD), Jordanian parents’ experiences have been overlooked. This study explored parents’ journeys toward receiving diagnoses for their children with ASD. In particular, it aimed to provide a [...] Read more.

Although extensive research has been conducted worldwide to investigate the diagnostic process of Autism Spectrum Disorder (ASD), Jordanian parents’ experiences have been overlooked. This study explored parents’ journeys toward receiving diagnoses for their children with ASD. In particular, it aimed to provide a clear picture of the process for obtaining these diagnoses for children in Jordan. Methods: Eighteen semi-structured interviews were carried out with 12 mothers and six fathers of children with ASD aged 5 to 11 years old. Results: The coding process was based on a thematic analysis method and resulted in the identification of three overlapping themes: dissatisfaction with professionals’ abilities to approach parents, an unstructured diagnostic process, and perspectives on diagnosis tools. Conclusions: Our data upheld the idea that parental satisfaction with the diagnostic process is influenced by the duration of the process, the information provided, the support offered, and the communication approach used by professionals. Within the local cultural context, parents were significantly impacted by the societal stigma associated with disability when they sought diagnoses for their children with ASD. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

► Show Figures

Figure 1

11 pages, 550 KiB

Open AccessArticle

Prospective One-Year Follow-Up of Sensory Processing in Phelan–McDermid Syndrome

by Sergio Serrada-Tejeda, Patricia Sánchez-Herrera-Baeza, Rosa M. Martínez-Piédrola, Nuria Máximo-Bocanegra, Nuria Trugeda-Pedrajo, M.ª Pilar Rodríguez-Pérez, Gemma Fernández-Gómez and Marta Pérez-de-Heredia-Torres

Children 2023, 10(6), 1086; https://doi.org/10.3390/children10061086 - 20 Jun 2023

Viewed by 1051

Abstract

Background: Phelan–McDermid syndrome (PMS) is caused by the loss (deletion) of a small portion of chromosome 22 in a region designated q13.3 (22q13.3 deletion). PMS is one of the most common genetic forms of autism spectrum disorder (ASD) in which sensory reactivity difficulties [...] Read more.

Background: Phelan–McDermid syndrome (PMS) is caused by the loss (deletion) of a small portion of chromosome 22 in a region designated q13.3 (22q13.3 deletion). PMS is one of the most common genetic forms of autism spectrum disorder (ASD) in which sensory reactivity difficulties have been described on limited occasions. Methods: The objective of this study is to identify whether changes in sensory reactivity skills occur after one year of follow-up in a group of 44 participants diagnosed with PMS. All participants completed the Short Sensory Profile (SSP). Two-factor ANOVA tests were performed with repeated measures for the study of the evolution of the scores. Results: Participants with PMS showed significant changes after one year of follow-up in sensory reactivity skills associated with tactile hyperreactivity (p = 0.003). The rest of the study variables did not show significant differences compared to the baseline assessment, showing definite differences associated with patterns of hypo-responsiveness and sensory seeking, low/weak energy, and difficulties in auditory filtering. Conclusions: Understanding the evolution of sensory reactivity skills can facilitate the adjustment to behavioral changes in people with PMS and design-targeted interventions to address sensory reactivity challenges. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

► Show Figures

Graphical abstract

Other

Jump to: Research

7 pages, 1043 KiB

Open AccessCase Report

Mimicking Hypoxic-Ischemic Encephalopathy in a Newborn with 21q Deletion Originating from Ring Chromosome 21

by Ja Un Moon and Sook Kyung Yum

Children 2023, 10(9), 1461; https://doi.org/10.3390/children10091461 - 27 Aug 2023

Viewed by 1073

Abstract

Partial deletion of the long arm (q) in chromosome 21 is an extremely rare condition with various phenotypes, including microcephaly, neurodevelopmental delay, dysmorphic features, and epileptic seizures. Neonatal hypoxic-ischemic encephalopathy (HIE) is an encephalopathy associated with a hypoxic-ischemic event in the brain where [...] Read more.

Partial deletion of the long arm (q) in chromosome 21 is an extremely rare condition with various phenotypes, including microcephaly, neurodevelopmental delay, dysmorphic features, and epileptic seizures. Neonatal hypoxic-ischemic encephalopathy (HIE) is an encephalopathy associated with a hypoxic-ischemic event in the brain where seizures usually occur in the earliest days of life. Neonatal encephalopathy is a distinct entity resulting from metabolic disorders, congenital infections or genetic abnormalities that could often mimic HIE features, leading to a misdiagnosis of HIE. Here, we present a case of a newborn who was initially misdiagnosed with HIE due to HIE-like features, and eventually was diagnosed to have a de novo ring chromosome 21 with 21q microdeletion. Clinical findings, including severe hypotonia with respiratory/feeding difficulties and intractable seizures, and radiologic findings of ischemic encephalopathy were discovered. Subsequent atypical findings of the clinical presentation ultimately led to her undergoing genetic testing confirming that she had a neonatal encephalopathy with a genetic abnormality. Our case highlights the importance of identifying non-HI neonatal encephalopathy by careful and structured evaluation for current history with a clinical course and a multidisciplinary approach including genetic testing, to provide an accurate diagnosis, treat curable inherited disorders, and develop future genetic counseling. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

► Show Figures

Graphical abstract

9 pages, 240 KiB

Open AccessCase Report

Occupational Therapy Intervention in the Child with Leukodystrophy: Case Report

by Rachele Simeon, Anna Berardi, Donatella Valente, Tiziana Volpi, Samuele Vagni and Giovanni Galeoto

Children 2023, 10(7), 1257; https://doi.org/10.3390/children10071257 - 21 Jul 2023

Viewed by 1022

Abstract

Background: There are many different types of Leukodystrophies. Specifically, children with hypomyelination and congenital cataract syndrome (HCC) in addition to motor retardation development, hypotonia and progressive spastic paraplegia, associated with cerebellar ataxia and peripheral neuropathy, have early bilateral cataracts and intellectual disability as [...] Read more.

Background: There are many different types of Leukodystrophies. Specifically, children with hypomyelination and congenital cataract syndrome (HCC) in addition to motor retardation development, hypotonia and progressive spastic paraplegia, associated with cerebellar ataxia and peripheral neuropathy, have early bilateral cataracts and intellectual disability as pathognomonic symptoms. HCC rehabilitation treatment is not well defined, but a significant amount of evidence in the literature has demonstrated the effectiveness of occupational therapy (OT) treatment in children with similar symptomatology. For this reason, the aim of this study was to describe the improvement in the autonomies and social participation of a child with HCC following OT treatment. Methods: A.E. was a 9-year-old child with HCC with severe intellectual disability. OT intervention lasted 3 months biweekly and each session lasted 45 min. Each session was divided into two parts: The first part aimed to increase the child’s active involvement through activities; the second part involved training in Activities of Daily living (ADL). The outcome measures were: ABILHAND-Kids; Pediatric Evaluation of Disability Inventory; Comprehensive OT Evaluation Scale; ADL and Instrumental Activities of Daily Living. Results: A.E.’s outcome measure reported an improvement from an autonomy standpoint and in the child’s general activity participation; there was also an increase in A.E.’s interpersonal skills. Conclusion: OT treatment improved A.E.’s autonomy. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

10 pages, 1970 KiB

Open AccessCase Report

Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in RTTN Gene: A Seckel Syndrome Case Report

by Behjat Ul Mudassir and Zehra Agha

Children 2023, 10(6), 1027; https://doi.org/10.3390/children10061027 - 08 Jun 2023

Cited by 1 | Viewed by 1625

Abstract

The RTTN gene encodes centriole biogenesis, replication, symmetry and cohesion, basal body organization and has recently been associated with the appearance of microcephaly syndromes. RTTN-related neurological defects including microcephaly, intellectual disability, congenital dwarfism, ophthalmic manifestations, and epilepsy are mainly due to abnormal [...] Read more.

The RTTN gene encodes centriole biogenesis, replication, symmetry and cohesion, basal body organization and has recently been associated with the appearance of microcephaly syndromes. RTTN-related neurological defects including microcephaly, intellectual disability, congenital dwarfism, ophthalmic manifestations, and epilepsy are mainly due to abnormal brain development pathways and loss-of-function protein mutations. We present a consanguineous Pakistani family clinically suspected of Seckel syndrome with severe microcephaly, severe intellectual disability, short stature, absence of speech, pointed nose, narrow face and bilateral cataract in two siblings residing in the suburbs of Islamabad. Forty cases of Seckel syndrome have been reported to date in the literature due to mutations in the ATR, TRAIP, RBBP8, NSMCE2, NIN, CENPJ, DNA2, CEP152 and CEP63 genes. The objective of the study was to perform a clinical diagnosis, genetic analysis, and pathophysiology of Seckel syndrome in the proband. Whole-exome sequencing discovered NM_173630.4: c.57G > T(pGlu19Asp) missense variant in exon 2 of the RTTN gene that co-segregates in the family. This novel variant, to the best of our knowledge, is pathogenic and with autosomal recessive inheritance expressed as Seckel syndrome in the affected members of the family. The present study has expanded the genetic knowledge of novel RTTN gene variants associated with Seckel syndrome and has broadened its phenotype spectrum in the Pakistani population, which comprises diverse ethnicities. We hope that our study will open new horizons for individual molecular diagnosis and therapeutics to improve the life of patients with this congenital syndrome. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

► Show Figures

Graphical abstract

9 pages, 500 KiB

Open AccessCase Report

A Novel Family with Demyelinating Charcot–Marie–Tooth Disease Caused by a Mutation in the PMP2 Gene: A Case Series of Nine Patients and a Brief Review of the Literature

by Margherita Baga, Susanna Rizzi, Carlotta Spagnoli, Daniele Frattini, Francesco Pisani and Carlo Fusco

Children 2023, 10(5), 901; https://doi.org/10.3390/children10050901 - 19 May 2023

Viewed by 1252

Abstract

Introduction: Charcot–Marie–Tooth (CMT) is a group of inherited peripheral neuropathies characterized by wide genotypic and phenotypic variability. The onset is typically in childhood, and the most frequent clinical manifestations are predominantly distal muscle weakness, hypoesthesia, foot deformity (pes cavus) and areflexia. In the [...] Read more.

Introduction: Charcot–Marie–Tooth (CMT) is a group of inherited peripheral neuropathies characterized by wide genotypic and phenotypic variability. The onset is typically in childhood, and the most frequent clinical manifestations are predominantly distal muscle weakness, hypoesthesia, foot deformity (pes cavus) and areflexia. In the long term, complications such as muscle-tendon retractions, extremity deformities, muscle atrophy and pain may occur. Among CMT1, demyelinating and autosomal dominant forms, CMT1G is determined by mutations in the PMP2 myelin protein. Results: Starting from the index case, we performed a clinical, electrophysiological, neuroradiological and genetic evaluation of all family members for three generations; we identified p.Ile50del in PMP2 in all the nine affected members. They presented a typical clinical phenotype, with childhood-onset variable severity between generations and a chronic demyelinating sensory-motor polyneuropathy on the electrophysiologic examination; the progression was slow to very slow and predominant in the lower limbs. Our study reports a relatively large sample of patients, members of the same family, with CMT1G by PMP2, which is a rare form of demyelinating CMT, highlighting the genetic variability of the CMT family instead of the overlapping clinical phenotypes within demyelinating forms. To date, only supportive and preventive measures for the most severe complications are available; therefore, we believe that early diagnosis (clinical, electrophysiological and genetic) allows access to specialist follow-up and therapies, thereby improving the quality of life of patients. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

► Show Figures

Figure 1

6 pages, 1909 KiB

Open AccessCase Report

Evaluating Dysfunction in Fever-Induced Paroxysmal Weakness and Encephalopathy

by Fumikazu Sano, Toshimichi Fukao, Hideaki Yagasaki, Hideaki Kanemura, Takeshi Inukai, Yoshimi Kaga and Takaya Nakane

Children 2023, 10(4), 703; https://doi.org/10.3390/children10040703 - 10 Apr 2023

Viewed by 1177

Abstract

Heterozygous variants in the ATP1A3 gene are linked to well-known neurological phenotypes. There has been growing evidence for a separate phenotype associated with variants in residue Arg756—fever-induced paroxysmal weakness and encephalopathy (FIPWE) or relapsing encephalopathy with cerebellar ataxia (RECA). With only about 20 [...] Read more.

Heterozygous variants in the ATP1A3 gene are linked to well-known neurological phenotypes. There has been growing evidence for a separate phenotype associated with variants in residue Arg756—fever-induced paroxysmal weakness and encephalopathy (FIPWE) or relapsing encephalopathy with cerebellar ataxia (RECA). With only about 20 cases being reported, the clinical features associated with mutations at Arg756 have not been fully elucidated. We report a case of FIPWE with a p.Arg756Cys change in the ATP1A3 gene and a comparison of the clinical features, including electrophysiological examination, with previous cases. The 3-year-old male patient had normal psychomotor development, presenting with recurrent symptoms of generalized hypotonia with loss of gait, mutism, and dystonic movements only during febrile illnesses since 19 months of age. At 2.7 years of age, a third neurological decompensation episode occurred, during which electroencephalography (EEG) did not reveal high voltage slow waves or epileptiform discharge. Nerve conduction studies (NCS) also did not show latency delay or amplitude reduction. ATP1A3 exon sequencing showed a heterozygous p.Arg756Cys mutation. While the patient experienced repeated encephalopathy-like episodes, including severe hypotonia during febrile illness, EEG and NCS did not reveal any obvious abnormalities. These electrophysiological findings may represent an opportunity to suspect FIPWE and RECA. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

► Show Figures

Figure 1

8 pages, 1543 KiB

Open AccessCase Report

First Reported Case of Gabriele-de Vries Syndrome with Spinal Dysraphism

by Nenad Koruga, Silvija Pušeljić, Marko Babić, Mario Ćuk, Andrea Cvitković Roić, Vjenceslav Vrtarić, Anamarija Soldo Koruga, Alen Rončević, Višnja Tomac, Tatjana Rotim, Tajana Turk, Domagoj Kretić, Nora Pušeljić, Rebeka Nađ and Ivana Serdarušić

Children 2023, 10(4), 623; https://doi.org/10.3390/children10040623 - 26 Mar 2023

Cited by 2 | Viewed by 1749

Abstract

Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in the Yin Yang 1 (YY1) gene. Individuals with this syndrome present with multiple congenital anomalies, as well as a delay in development and intellectual disability. [...] Read more.

Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in the Yin Yang 1 (YY1) gene. Individuals with this syndrome present with multiple congenital anomalies, as well as a delay in development and intellectual disability. Herein, we report the case of a newborn male patient with a novel de novo pathogenic variant in the Guanine Nucleotide-Binding Protein, Alpha Stimulating (GNAS) gene, which was identified by whole-exome sequencing. Our patient suffered from a large open spinal dysraphism which was treated surgically immediately after birth. During the follow-up, facial dysmorphism, bladder and bowel incontinence, and mildly delayed motor and speech development were observed. Congenital central nervous system disorders were also confirmed radiologically. In this case report, we present our diagnostic and treatment approaches to this patient. To our knowledge, this is the first reported case of Gabriele-de Vries syndrome presenting with spinal dysraphism. Extensive genetic evaluation is the cornerstone in treatment of patients with suspected Gabriele-de Vries syndrome. However, in cases with potentially life-threatening conditions, surgery should be strongly considered. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

► Show Figures

Figure 1

18 pages, 2543 KiB

Open AccessSystematic Review

Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

by Mario Mastrangelo, Valentina Gasparri, Katerina Bernardi, Silvia Foglietta, Georgia Ramantani and Francesco Pisani

Children 2023, 10(3), 553; https://doi.org/10.3390/children10030553 - 15 Mar 2023

Cited by 3 | Viewed by 2274

Abstract

Background: Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects). Patients and methods: We conducted a systematic review of published pediatric cases with [...] Read more.

Background: Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects). Patients and methods: We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected. Results: 497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed. Conclusions: Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG. Full article

(This article belongs to the Special Issue Neurological Diseases in Children and Adolescent)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Neurological Diseases in Children and Adolescent

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (10 papers)

Research

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI