Delayed Psychomotor Development Research Articles

A vegetable fat-based diet delays psychomotor and cognitive development compared with maternal dairy fat intake in infant gray mouse lemurs

Dairy fat has a unique lipid profile; it is rich in short- and medium-chain saturated fatty acids that induce ketone production and has a balanced ω6/ω3 ratio that promotes cognitive development in early life. Moreover, the high consumption of vegetable oils in pregnant and lactating women raises concerns regarding the quality of lipids provided to offspring. Here, we investigate maternal dairy fat intake during gestation and lactation in a highly valuable primate model for infant nutritional studies, the gray mouse lemur (Microcebus murinus). Two experimental diets are provided to gestant mouse lemurs: a dairy fat-based (DF) or vegetable fat-based diet (VF). The psychomotor performance of neonates is tested during their first 30 days. Across all tasks, we observe more successful neonates born to mothers fed a DF diet. A greater rate of falls is observed in 8-day-old VF neonates, which is associated with delayed psychomotor development. Our findings suggest the potential benefits of lipids originating from a lactovegetarian diet compared with those originating from a vegan diet for the psychomotor development of neonates.

Epidemiological, Clinical and Therapeutic Aspects of Neuropaediatric Emergencies in Children Aged 1 Month to 15 Years in the Paediatric Emergency Department of CHU-Gabriel Toure

Introduction: Paediatric neurological emergencies are a major public health problem worldwide, in Africa and in Mali. Despite the scale and complexity of paediatric neurological emergencies, there is little data in the literature in Africa and particularly in Mali on these neurological disorders in paediatrics. Aim: The aim of our study was to examine the epidemiological, clinical and therapeutic aspects of neuropaediatric emergencies in children aged between 1 month and 15 years in the paediatric department of the CHU-Gabriel Touré in 2021. Patients and Methods: This was a cross-sectional study conducted over a twelve-month period (01 January to 31 January 2021) in children aged 1 month to 15 years hospitalised in the paediatric emergency department for a neurological emergency. Results: The frequency of hospitalization was 18.35%. The age group 12 to 60 months accounted for 43.7%. The sex ratio was 1.44. Convulsion was the most frequent reason for hospitalisation (49.3%). Delayed psychomotor development was noted in 4%. Around 3% of the children had not been vaccinated. On clinical neurological examination, the signs observed were : Altered consciousness (88.3%), convulsion (61%), and axial hypotonia (29%). Focal convulsions accounted for 59%, and 45.7% were febrile. The main diagnoses were neuromalaria, hyperpyretic convulsion and meningitis (68.3%, 7% and 6.3% respectively). The death rate within the first 24 hours was 48%. The average length of hospitalisation was 5.03 +/-4.5 days, with extremes of 1 and 21 days. Conclusion: Neuropaediatric emergencies are a major paediatric health problem. They are frequent and contribute substantially to infant and child mortality in our context.

First-trimester fetal size, accelerated growth in utero, and child neurodevelopment in a cohort study.

Early pregnancy is a critical window for neural system programming; however, the association of first-trimester fetal size with children's neurodevelopment remains to be assessed. This study aimed to explore the association between first-trimester fetal size and children's neurodevelopment and to examine whether intrauterine accelerated growth could compensate for the detrimental effects of first-trimester restricted growth on childhood neurodevelopment. The participants were from a birth cohort enrolled from March 2014 to March 2019 in Wuhan, China. A total of 2058 fetuses with crown to rump length (CRL) (a proxy of first-trimester fetal size) measurements in the first trimester and neurodevelopmental assessment at age 2 years were included. We measured the first-trimester CRL and defined three fetal growth patterns based on the growth rate of estimated fetal weight from mid to late pregnancy. The neurodevelopment was assessed using the Bayley Scales of Infant Development of China Revision at 2 years. Each unit (a Z score) increase of first-trimester CRL was associated with increased scores in mental developmental index (MDI) (adjusted beta estimate = 1.19, (95% CI: 0.42, 1.95), P = 0.03) and psychomotor developmental index (PDI) (adjusted beta estimate = 1.36, (95% CI: 0.46, 2.26), P < 0.01) at age 2 years, respectively. No significant association was observed between fetal growth rate and PDI. For children with restricted first-trimester fetal size (the lowest tertile of first-trimester CRL), those with "intrauterine accelerated growth" pattern (higher growth rates) had significantly higher MDI (adjusted beta estimate = 6.14, (95% CI: 3.80, 8.49), P < 0.001) but indistinguishable PDI compared to those with "intrauterine faltering growth" pattern (lower growth rates). Main limitations of this study included potential misclassification of gestational age due to recall bias of the last menstrual period and residual confounding. The current study suggests that restricted first-trimester fetal size is associated with mental and psychomotor developmental delay in childhood. However, in children with restricted first-trimester fetal size, intrauterine accelerated growth was associated with improved mental development but had little effect on psychomotor development. Additional studies are needed to validate the results in diverse populations.

ETIOLOGICAL REVIEW OF BRAIN INJURIES ON CT SCANNING IN THE ASSESSMENT OF PSYCHOMOTOR DEVELOPMENT DELAY IN CHILDREN UNDER FIVE (5) YEARS OF AGE AT THE LUXEMBOURG MOTHER-CHILD CHU

Objective: Our workaimed to describe the scan semiology of lesionsencountered in delayedpsychomotordevelopment (DPMD) in childrenunder 5 yearsold at the Mother-Child University Hospital Center Le Luxembourg Methodology:This is a prospective analytical and descriptive studycarried out over a period of 18 months (from April 15, 2021 to September 15, 2022) in the radiologydepartment of the CHU-ME Mère et Enfant Le Luxembourg. It concerned all patients aged 0 to 5 yearsadmitted to the medicalimagingdepartment of the Luxembourg Mother and Child University Hospital for psychomotordelaywhohadundergone a brain scan. Childrenwithoutpsychomotordelaywereexcludedfromourstudy. Results:Weretained 150 cases of psychomotordelayduringourstudyperiod. The age group of 0 to 02 yearswas the majority (67%) with an average of 1.33 years, an extreme of 1 month to 5 years and standard deviation of 5.807. The male genderwas in the majoritywith (55%) with a sex ratio of 1.22.The mostcommon type of deliverywas normal deliverywith a frequency of 62.0%. Prematuritywas the mostrepresentedobstetricrisk factor (18.0%).Convulsion was the mostrepresentedneonatalrisk factor (16.7%).Epilepsywas the mostcommon postnatal neurologicalantecedent (6.7%). The scan resultwasabnormalin 75% of our patients. The lesionsfoundwere:anoxo-ischemicleukoencephalopathy (47%), hydrocephalus (17%), malformative lesions (7%), sequelae of brain infections(3%) and tuberoussclerosis of Bourneville (1%) Conclusion: ChildhoodDPMDrepresents a major healthproblemwith a relatively high prevalence. This studydemonstrates the diagnostic value of CT in the exploration of RPM in children. Of the 150 patients explored, brain CT revealed a lesionin 75.0% of cases.

Evaluation of academic performance and social integration of children operated for hydrocephalus in Cameroon.

Low intelligence quotient (IQ) and delayed psychomotor development (DPD) are formidable complications of hydrocephalus. The aim of this study was to evaluate the academic performance and social integration of children operated on for hydrocephalus in Cameroon. The authors present a cross-sectional study with retrospective data collection from January 2010 to May 2020. All children less than 10years of age who had undergone surgery for a ventriculo-peritoneal shunt indicated for hydrocephalus with a post-operative evolution of 7 to 10years and who were attending school were included. Academic performance was assessed using the Wechsler Intelligence Scale for Children IV (WISC IV), and social integration was assessed using the Vineland II score. Of the 45 children aged 7 to 10years who attended school and were followed-up, the sex ratio was 1.25 in favor of males. 77.8% of these children had a malformation with paralysis being the most common functional sequela (29%). 73.3% of our patients had good social integration. Fifty-three percent of patients had reduced academic performance, with non-verbal performance being the most frequent (62.2%). Long-term memory was the most impaired, with 73.3% having a very low speed of information processing. Non-verbal performance was the most affected (62.2%) particularly long-term memory. Forty percent had an IQ below 70. The statistically significant determinants of social integration were age, sex, malformative etiology, and good psychomotor development, and the statistically significant determinants of educational delay were age, malformative etiology, IQ below 70, and time to care. Academic performance was reduced in more than half of our patients, but most of them had good social integration. Early diagnosis and management improve the chances of good psychomotor development and IQ.

Comparative analysis of long-term results of surgical treatment of children with basal encephaloceles

Basal encephaloceles (skull base hernias) are a rare pathology manifested by prolapse of altered membranes and brain tissue through a bone defect of the skull base. Endoscopic access is safer and is currently used as the method of choice in the treatment of this pathology. Available literature studies do not cover the quality of life of these patients at follow-up. There is a controversy regarding the impact of endoscopic access on the growth centers of the facial skeleton. Material and methods. A retrospective analysis of a series of 100 patients aged 0 to 18 years with basal encephaloceles who underwent surgical treatment at the N. N. Burdenko National Medical Research Center of Neurosurgery from 2005 to 2022 was carried out to determine the effectiveness and safety of the endoscopic method in the treatment of patients with basal encephaloceles and identify factors affecting the quality of life of these patients. Results and conclusions. Endoscopic endonasal access in the treatment of children with basal encephaloceles is effective and safe. Patients have a high quality of life (&gt;85 points) at follow-up. After the operation, there is an improvement in nasal breathing and an increase in the degree of psychomotor development. Patients have a high quality of life (&gt;85 points) at follow-up. A lower quality of life at follow-up was observed in children with delayed psychomotor development before surgery (OR=0.6; p=0.003). The follow-up study of the dynamics of craniometric parameters did not reliably show any disturbances in the growth of the bones of the facial skeleton in patients after endoscopic surgery.

Clinical and molecular cytogenetic studies of five new patients with 20q11q12 deletion and review of the literature: Proposition of two critical regions.

Deletions of the long arm of chromosome 20 (20q) are rare, with only 16 reported patients displaying a proximal interstitial 20q deletion. A 1.62 Mb minimal critical region at 20q11.2, encompassing three genes GDF5, EPB41L1, and SAMHD1, is proposed to be responsible for this syndrome. The leading clinical features include growth retardation, intractable feeding difficulties with gastroesophageal reflux, hypotonia and psychomotor developmental delay. Common facial dysmorphisms including triangular face, hypertelorism, and hypoplastic alae nasi were additionally reported. Here, we present the clinical and molecular findings of five new patients with proximal interstitial 20q deletions. We analyzed the phenotype and molecular data of all previously reported patients with 20q11.2q12 microdeletions, along with our five new cases. Copy number variation analysis of patients in our cohort has enabled us to identify the second critical region in the 20q11.2q12 region and redefine the first region that is initially identified. The first critical region spans 359 kb at 20q11.2, containing six MIM genes, including two disease-causing genes, GDF5 and CEP250. The second critical region spans 706 kb at 20q12, encompassing four MIM genes, including two disease-causing genes, MAFB and TOP1. We propose GDF5 to be the primary candidate gene generating the phenotype of patients with 20q11.2 deletions. Moreover, we hypothesize TOP1 as a potential candidate gene for the second critical region at 20q12. Of note, we cannot exclude the possibility of a synergistic role of other genes involved in the deletion, including a contiguous gene deletion syndrome or position effect affecting both critical regions. Further studies focusing on patients with proximal 20q deletions are required to support our hypothesis.

Autosomal recessive primary microcephaly type 2 associated with a novel WDR62 splicing variant that disrupts the expression of the functional transcript.

Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized primarily by congenital microcephaly and intellectual disability but without extra-central nervous system malformations. This investigation aimed to elucidate the genetic underpinnings of microcephaly in a patient from a Chinese consanguineous family. A comprehensive clinical assessment, including brain magnetic resonance imaging (MRI), electroencephalogram (EEG), and genetic analyses, was conducted to evaluate the patient's condition. Whole-exome sequencing (WES) was employed to identify the causative gene, followed by Sanger sequencing, to confirm the mutation and its segregation within the family. Reverse transcript polymerase chain reaction (RT-PCR) was utilized to detect changes in splicing. Western blot was employed to reveal the difference of protein expression level between the wild-type and mutant WDR62 in vitro. The patient exhibited classic MCPH symptoms, including microcephaly, recurrent epilepsy, delayed psychomotor development, and intellectual disability. Additionally, asymmetrical limb length was noted as a prominent feature. MRI findings indicated reduced brain volume with cortical malformations, while EEG demonstrated heightened sharp wave activity. A molecular analysis uncovered a novel homozygous variant c.4154-6 C > G in the WDR62 intron, and a functional analysis confirmed the pathogenicity of this mutation, resulting in the formation of an abnormal transcript with premature termination codons. This study enhances our understanding of the genetic heterogeneity associated with MCPH and highlights the pivotal role of genetic testing in the diagnosing and managing of rare neurodevelopmental disorders. Furthermore, it highlights the potential of emerging genetic therapies in treating conditions such as MCPH2.

Perinatal depression trajectories and child development at one year: a study in China

BackgroundThe objective of the current study was to investigate the correlation between trajectories of maternal perinatal depression (PND) spanning from early pregnancy to one year postpartum and developmental delays observed in one-year-old children.MethodsThe dataset under examination encompassed 880 women who took part in a mother-child birth study conducted in China. Latent class growth analysis (LCGA) was employed to identify patterns in Edinburgh Postnatal Depression Scale (EPDS) scores of women, spanning from early pregnancy to one year postpartum. To assess the neurodevelopment of one-year-old children, a Chinese version of the Bayley Scale of Infant Development (BSID-CR) was employed. Logistic regression was employed to explore the association between PND trajectories and developmental delays in children, with appropriate covariate adjustments.ResultsThe trajectories of maternal PND identified in this study included a minimal-stable symptom group (n = 155), low-stable symptom group (n = 411), mild-stable symptom group (n = 251), and moderate-stable symptom group (n = 63). Logistic regression analysis revealed that mothers falling into the moderate-stable symptom group exhibited a notably heightened risk of having a child with psychomotor developmental delays at the age of one year.ConclusionsThe findings drawn from a representative sample in China provide compelling empirical evidence that bolsters the association between maternal PND and the probability of psychomotor developmental delays in children. It is imperative to develop tailored intervention strategies and meticulously design mother-infant interactive intervention programs for women with PND.

Синдром микроцефалии с капиллярными мальформациями: клинический случай

ABSTRACT INTRODUCTION. Microcephaly-capillary malformation syndrome (MIC-CAP syndrome; OMIM: 614261) is a rare severe autosomal recessive disorder characterized mainly by congenital microcephaly, multiple small capillary malformations of the skin, and drugresistant epilepsy with early onset. The disease results from a mutation in the STAMBP gene. To date, the worldwide prevalence is less than 1:1000000 and less than 30 cases have been described. CASE PRESENTATION. We present a case of MIC-CAP syndrome in a child with a homozygous mutation NC_000002.12: g.73831044A&gt;G (c.188A&gt;G, p.Tyr63Cys) in the STAMBP gene. In the clinical picture: congenital microcephaly, multiple capillary malformations, drug-resistant epilepsy with early onset, gross psycho-motor developmental delay. CONCLUSION. The presented case has all the main characteristic symptoms of the clinical picture of MIC-CAP syndrome. The peculiarity of the case can be considered the presence of renal multicystosis, which has not been previously described in this syndrome. In antiepileptic therapy, the best effect was obtained on duotherapy with valproate and vigabatrin with course addition of clobazam. Given the typical symptom complex of this syndrome, it is advisable to immediately search for a mutation in the STAMBP gene. KEYWORDS: microcephaly, capillary malformations, STAMBP gene, drug-resistant epilepsy

Alloparental Support and Infant Psychomotor Developmental Delay

Receiving social support from community and extended family has been typical for mothers with infants in human societies past and present. In non-industrialised contexts, infants of mothers with extended family support often have better health and higher survival through the vulnerable infant period, and hence shared infant care has a clear fitness benefit. However, there is scant evidence that these benefits continue in industrialised contexts. Better infant health and development with allocare support would indicate continued evolutionary selection for allocare. The research reported here used multiple logistic regression analysis to test whether a lack of family and other social support for mothers was associated with an increased risk of developmental delay in 9-month-old infants in the UK Millennium Cohort (analysis sample size, 15,696 infants). Extended family-based childcare during work hours and more maternal time spent with friends were the most influential kin and social support variables: infants of mothers with kin-based childcare versus all other childcare arrangements had a lower risk of developmental delay (OR = 0.61, 95% CIs: 0.46–0.82). Infants of mothers who spent no time with friends when compared with those who saw friends every day had double the odds of delay. Greater paternal involvement in infant care was associated with a lower odds of developmental delay. In conclusion, shared care of infants and social support for mothers may influence fitness-related traits in industrialised societies rather than being factors that influenced selection only in the past and in societies which retain close kin networks and a strong local community focus.

Neurodevelopmental outcomes after prenatal exposure to lamotrigine monotherapy in women with epilepsy: a systematic review and meta-analysis

BackgroundLamotrigine has become one of the most commonly prescribed antiseizure medications (ASM) in epileptic women during pregnancy and therefore requires regular updates regarding its safety. The aim of this study was to estimate the association between in utero exposure to lamotrigine monotherapy and the occurrence of neurodevelopmental outcomes.MethodsAll comparative studies assessing the occurrence of neurodevelopmental outcomes after epilepsy-indicated lamotrigine monotherapy exposure during pregnancy were searched. First, references were identified through a snowballing approach, then, through electronic databases (Medline and Embase) from 2015 to June 2022. One investigator evaluated study eligibility and extracted data and a second independent investigator reviewed the meta-analysis (MA). A systematic review and random-effects model approach were performed using a collaborative WEB-based meta-analysis platform (metaPreg.org) with a registered protocol (osf.io/u4gva).ResultsOverall, 18 studies were included. For outcomes reported by at least 4 studies, the pooled odds ratios and 95% confidence interval obtained with the number of exposed (N1) and unexposed children (N0) included were: neurodevelopmental disorders as a whole 0.84 [0.66;1.06] (N1 = 5,271; N0 = 22,230); language disorders or delay 1.16 [0.67;2.00] (N1 = 313; N0 = 506); diagnosis or risk of ASD 0.97 [0.61;1.53] (N1 = at least 5,262; N0 = 33,313); diagnosis or risk of ADHD 1.14 [0.75;1.72] (N1 = at least 113; N0 = 11,530) and psychomotor developmental disorders or delay 2.68 [1.29–5.56] (N1 = 163; N0 = 220). The MA of cognitive outcomes included less than 4 studies and retrieved a significant association for infants exposed to lamotrigine younger than 3 years old but not in the older age groups.ConclusionPrenatal exposure to lamotrigine monotherapy is not found to be statistically associated with neurodevelopmental disorders as a whole, language disorders or delay, diagnosis or risk of ASD and diagnosis or risk of ADHD. However, the MA found an increased risk of psychomotor developmental disorders or delay and cognitive developmental delay in less than 3 years old children. Nevertheless, these findings were based exclusively on observational studies presenting biases and on a limited number of included children. More studies should assess neurodevelopmental outcomes in children prenatally exposed to lamotrigine.

"Molar Tooth" Sign Pathognomonic of Joubert Syndrome

Joubert syndrome is a rare autosomal disorder characterised by abnormal respiratory patterns, delayed psychomotor development, visual disturbances and renal and hepatic involvement. We report the case of a 7-year-old girl who presented with delayed psychomotor development. Neurological examination revealed hypotonia. No respiratory disorders were observed in our case. Magnetic resonance imaging revealed the pathognomonic sign of the molar tooth in the posterior cerebral fossa.

PTCHD1 gene mutation/deletion: the cognitive-behavioral phenotyping of four case reports.

X-linked PTCHD1 gene has recently been pointed as one of the most interesting candidates for involvement in neurodevelopmental disorders (NDs), such as intellectual disability (ID) and autism spectrum disorder (ASD). PTCHD1 encodes the patched domain-containing protein 1 (PTCHD1), which is mainly expressed in the developing brain and adult brain tissues. To date, major studies have focused on the biological function of the PTCHD1 gene, while the mechanisms underlying neuronal alterations and the cognitive-behavioral phenotype associated with mutations still remain unclear. With the aim of incorporating information on the clinical profile of affected individuals and enhancing the characterization of the genotype-phenotype correlation, in this study, we analyze the clinical features of four individuals (two children and two adults) in which array-CGH detected a PTCHD1 deletion or in which panel for screening non-syndromal XLID (X-linked ID) detected a PTCHD1 gene variant. We define the neuropsychological and psychopathological profiles, providing quantitative data from standardized evaluations. The assessment consisted of clinical observations, structured interviews, and parent/self-reported questionnaires. Our descriptive analysis align with previous findings on the involvement of the PTCHD1 gene in NDs. Specifically, our patients exhibited a clinical phenotype characterized by psychomotor developmental delay- ID of varying severity. Interestingly, while ID during early childhood was associated with autistic-like symptomatology, this interrelation was no longer observed in the adult subjects. Furthermore, our cohort did not display peculiar dysmorphic features, congenital abnormalities or comorbidity with epilepsy. Our analysis shows that the psychopathological and behavioral comorbidities along with cognitive impairment interfere with development, therefore contributing to the severity of disability associated with PTCHD1 gene mutation. Awareness of this profile by professionals and caregivers can promote prompt diagnosis as well as early cognitive and occupational enhancement interventions.

A novel 11 base pair deletion in KMT2C resulting in Kleefstra syndrome 2.

Haploinsufficiency of the Lysine Methyltransferase 2C (KMT2C) gene results in the autosomal dominant disorder, Kleefstra syndrome 2. It is an extremely rare neurodevelopmental condition, with 14 previous reports describing varied clinical manifestations including dysmorphic features, delayed psychomotor development and delayed growth. Here, we describe a female with global developmental delay, attention deficit disorder, dyspraxia, short stature and subtle non-specific dysmorphic features. To identify causative mutations, whole exome sequencing was performed on the proband and her younger brother with discrete clinical presentation. Whole exome sequencing identified a novel de novo heterozygous 11 bp deletion in KMT2C (c.1759_1769del), resulting in a frameshift mutation and early termination of the protein (p.Gln587SerfsTer7). This variant is the second-most N-terminal reported mutation, located 4171 amino acids upstream of the critical enzymatically active SET domain (required for chromatin modification and histone methylation). The majority of the other reported mutations are frameshift mutations upstream of the SET domain and are predicted to result in protein truncation. It is thought that truncation of the SET domain, results functionally in an inability to modify chromatin through histone methylation. This report expands the clinical and genetic characterisation of Kleefstra syndrome 2.

Long-term consequences of acute toxic prenatal hypoxia induced by sodium nitrite in rat experiments

Introduction. Gestational hypoxia plays an important role in fetal development, as it causes the development of oxidative stress and delayed psychomotor development. The aim of the study was to evaluate the prenatal effect of sodium nitrite on indices characterizing orienting and exploratory activity, mental activity and the degree of hypoxia in rat offspring. Materials and methods. Acute hypoxia was modeled by administration of sodium nitrite at a dose of 30 mg/kg intramuscularly to five pregnant rats during 16–19 days of gestation. Five females constituted a control group. In 50 born rats, orientation and exploration activity, cognitive functions, intensity of lipid peroxidation and glycolysis were studied. Results. The offspring of females that underwent acute hypoxia significantly lagged behind in the positive dynamics of body weight gain compared to control individuals. Thirty-day-old rats showed a pronounced disorder of the structure of behavioral pattern, learning process and long-term memory, increased content of diene conjugates, malonic dialdehyde and the level of lactate dehydrogenase activity in blood. Discussion. It was found that offspring whose mothers suffered acute hypoxia of toxic genesis developed pronounced behavioral disorders of psychomotor agitation and cognitive dysfunction characterized by decreased learning ability and impaired long-term memory. The content of primary and secondary products of lipid peroxidation and lactate dehydrogenase was increased in rats. The development of cellular oxidative stress under conditions of intrauterine hypoxia leads to oxygen deficiency in the fetus and a switch from tissue respiration to glycolysis, which underlies CNS damage. Conclusion. It was shown that sodium nitrite administration during the period from the 16th to the 19th day of gestation caused hyperactivity, depressed emotional status, and decreased orienting and exploratory activity and the ability to learn and retain a memory trace in rat offspring. Increased levels of diene conjugates and malonic dialdehyde, lactate dehydrogenase activity were observed in rats.

A Rare Cause of Hypotonia: 49,XXXXX (Pentasomy X)

Pentasomy X syndrome is a very rare sex chromosome numerical anomaly of unknown frequency. The karyotype consists of 49,XXXXX. Musculoskeletal, craniofacial, cardiac, and kidney anomalies accompany psychomotor developmental delays. This report describes, a 16-month-old girl who presented to the pediatric neurology outpatient clinic with complaints of joint laxity and inability to hold her head upright from the age of 3-4 months. The patient exhibited dysmorphic facial features and hand-foot deformities. Genetic consultation was requested, and cytogenetic examination revealed a 49,XXXXX chromosomal anomaly. The most prominent clinical feature of 49,XXXXX patients with pentasomy is severe hypotonia. This article emphasizes the importance of cytogenetic analysis in the evaluation of hypotonicity.

Schizencephaly: A Case Report

Schizencephaly is a rare anomaly of embryonic development characterized by the presence of linear fissures containing cerebrospinal fluid and lined with dysplastic gray matter, extending from the pial surface of the cerebral hemisphere to the ependymal surface of the lateral ventricle. Schizencephaly can affect one or both cerebral hemispheres, leading to a variety of neurological symptoms such as epilepsy, motor deficits and psychomotor retardation. An antenatal diagnosis can be made; treatment is based on rehabilitation, antiepileptic drugs and supportive psychotherapy.&#x0D; We report the case of a 3-year-old child admitted to our department for a generalized tonicoclonic convulsive seizure resistant to antiepileptic treatment. The child's antecedents included a well-monitored pregnancy carried to term, and a vaginal delivery with no evidence of neonatal distress. The parents are not consanguineous, but there have been two deaths in the siblings (at 15 days and 40 days) of unknown origin. The child also showed delayed psychomotor development.&#x0D; An MRI scan revealed a type 1 right schizencephaly with a closed cleft, but biology revealed no abnormalities, and genetic studies are still in progress.&#x0D; Management to date is based on antiepileptic drugs, psychomotor rehabilitation and sometimes surgery.

Infantile Metachromatic Leukodystrophy: Case Report

Metachromatic Leukodystrophy (MLD) is typically characterized by the accumulation of sulfatide in various organs, including the central nervous system. This accumulation leads to neurological and mental symptoms. A case of a two-year-old male patient with a history of psychomotor retardation, developmental delay, and poor overall performance is reported. The patient’s imaging findings are compatible with Leukodystrophy. The aim of this case report is to identify the clinical presentation and typical MRI features that can help diagnose MLD, even in the absence of an enzyme assay or gene mutation investigation.

PMPCA-Related Encephalopathy: Novel Variants, Phenotype Extension, and Mitochondrial Morphology.

The PMPCA gene encodes the α-subunit of mitochondrial processing peptidase (α-MPP), an enzyme responsible for cleavage of nuclear-encoded mitochondrial precursor proteins after their import into mitochondria. Mutations in this gene have been described in patients with nonprogressive or slow progressive cerebellar ataxia, with variable age at onset and severity. Cerebellar atrophy and striatum changes were found in severe cases. The patient was diagnosed using whole exome sequencing. Skin fibroblasts were used for confirmation of α-MPP levels using western blot and mitochondrial morphology assessment of immunofluorescent confocal microscopy images. Two novel compound heterozygous variants in the PMPCA gene (p.Tyr241Ser and p.Met251Val) were identified in an 8-year-old proband with progressive spastic quadriparesis, delayed psychomotor development, and intellectual disability, with onset at 13 months. The brain imaging showed cortical and cerebellar atrophy, reduced volume of basal ganglia with striatum hyperintensity, and periventricular white matter changes. The patient's fibroblasts showed a decreased α-MPP level and reduced and fragmented mitochondria. The described case contributes to the number of patients with progressive PMPCA-related disease with a severe intermediate phenotype. Moreover, we extend the phenotype to Leigh-like white matter changes that have not been described in previously reported cases.