Delayed Speech Development Research Articles

Features of neurological status in children with autism spectrum disorders

The article analyzes the features of the neurological status, characterizes group differences in motor functions in children with autism spectrum disorders depending on the presence and severity of delayed psychological and speech development.Material and methods. The analysis of data on the neurological status of children with autism spectrum disorders was based on 51 patients records for the period from 2016 to 2021; 43 boys (84%) and 8 girls (16%) aged 3 to 10 years. All patients were divided into 2 groups according to the criterion of the presence or absence of a severe delay in psychological and speech development. The first group included children with severe forms of delayed psychological and speech development — 23 (45%), the second — 28 (55%) patients with mild forms or without delayed psychological and speech development.Results. The children in the first group were characterized by the predominance of diffuse muscular hypotension (96%); stereotypies manifested in movements looking like «wings» (22%), other stereotyped movements (48%); disorders such as echolalia, ataxia, pyramidal insufficiency syndrome, and strabismus were equally common in both groups.Conclusion. Analysis of the data showed the predominance of several neurological disorders in children with autism spectrum disorders who have a severe delay in psychological and speech development and made it possible to identify neurological characteristics of children with autism spectrum disorders regardless of the level of psychological and speech development.

Neonatal management and outcome in complicated monochorionic twins: What have we learned in the past decade and what should you know?

Monochorionic (MC) twin pregnancies are at increased risk of neonatal morbidity and mortality due to the shared placenta with vascular connections that can give rise to various complications, including twin-twin transfusion syndrome, twin anemia polycythemia sequence (TAPS), selective fetal growth restriction, and other hematological imbalances at birth. Each complication presents its own challenges and considerations in the neonatal period. Measurement of hemoglobin levels and reticulocyte count is required to establish a correct diagnosis. Placenta dye injection is needed to properly distinguish between the various conditions. Risk factors for adverse outcome in MC twins include prematurity, severe cerebral injury, and the type of MC pregnancy complication. We, therefore, recommend cerebral ultrasound examinations in all complicated MC twins at birth to rule out a severe brain injury. Lastly, we strongly encourage screening for hearing loss using automated auditory brainstem response in all spontaneous TAPS donors to prevent permanent speech development delay.

Provider Perspectives: Identification and Follow-up of Infants who Are Deaf or Hard of Hearing.

Without timely screening, diagnosis, and intervention, hearing loss can cause significant delays in a child's speech, language, social, and emotional development. In 2019, Texas had nearly twice the average rate of loss to follow-up (LFU) or loss to documentation (LTD; i.e., missing documentation of services received) among infants who did not pass their newborn hearing screening compared to the United States overall (51.1 vs. 27.5%). We aimed to identify factors contributing to LFU/LTD among infants who do not pass their newborn hearing screening in Texas. Data were collected through semistructured qualitative interviews with 56 providers along the hearing care continuum, including hospital newborn hearing screening program staff, audiologists, primary care physicians, and early intervention (EI) program staff located in three rural and urban public health regions in Texas. Following recording and transcription of the interviews, we used qualitative data analysis software to analyze themes using a conventional content analysis approach. Frequently cited barriers included problems with family access to care, difficulty contacting patients, problems with communication between providers and referrals, lack of knowledge among providers and parents, and problems using the online reporting system. Providers in rural areas more often mentioned problems with family access to care and contacting families compared to providers in urban areas. These findings provide insight into strategies that public health professionals and health care providers can use to work together to help further increase the number of children identified early who may benefit from EI services. · Infants with suspected hearing loss may not receive timely diagnosis or early intervention.. · We interviewed healthcare providers in Texas along the hearing care continuum.. · Findings suggest strategies to increase the number of children with hearing loss identified early..

Cytogenetic techniques in current biomedical research. PART III: numerical alterations of human karyotype

Numerical abnormalities of karyotype are the result of genome mutations. Unlike gene and chromosomal abnormalities, genome mutations do not disrupt the structure of DNA or chromosomes. The cause of numerical changes in the karyotype is a violation of the mechanism of chromosome segregation during meiosis or mitosis. Like other mutations, genome mutations are a natural mechanism for increasing of genetic diversity in offspring. At the same time, humans usually have negative effects of any numerical deviations from the norm, for this reason, cytogenetic examination of aneuploidies is an important diagnostic tool in medical genetics.A change in the number of sex chromosomes is usually not lethal. The spectrum of detected deviations in the carrier is from inconstant impairment of reproduction but a normal phenotype to malformations of some internal organs, infertility and severe intellectual disabilities. Aneuploidies of autosomes are always a threat to life and health. Only autosomal trisomies on chromosomes 13, 18, 21 and 22 are compatible with live birth, there are solitary reports of the birth of children with polyploidies. At the same time, the prognosis of life is relatively favorable only in the case of trisomy 21, leading to the formation of Down syndrome. Other aneuploidies usually lead to spontaneous termination of pregnancy in the early stages and are discovered in samples of abortion material.In this regard, cytogenetic analysis of chromosomal aneuploidies is used to establish the genetic cause of anomalies and malformations in the postnatal period, delays in speech and psychomotor development, reproduction disorders in adults. Of particular importance is the cytogenetic analysis of the karyotype of embryos in the prenatal period. The proposed lecture analyzes the mechanism of formation of genomic mutations and their diversity. The possible medical consequences of the presence of various types of aneuploidies are considered. To the reader attention is offered syndromes associated with a change in the number of chromosomes in the karyotype. The description is illustrated by real images of patient karyotypes.The lecture is aimed primarily at students of medical and biological specialties, young specialists who plan to use cytogenetic research methods in their practical activities, and doctors who are faced with the need to analyze and interpret the results of cytogenetic analysis. To assimilate the material under discussion, it is recommended to familiarize yourself with the previous lecture of the cycle.

Artificial Neural Network in Prediction of Language Delay in Children Under 1 Year: Preliminary Results

Background: the delay in language development is characterized by qualitative and quantitative underdevelopment of the vocabulary and the lack of formation of expressive speech. This violation belongs to the mildest speech pathologies, however, there is a high probability of the presence of concomitant mental pathology and the occurrence of adaptation problems at school age. In the etiology of delayed language development, its multifactorial nature has been established. Thus, there is a need to develop a tool that predicts the formation of a delay in speech development in children for the timely implementation of preventive measures.Aim of the study: to develop a tool for predicting speech development delay in children under one year old using artificial intelligence algorithms.Patients and methods: 196 children were examined. The mean age was 26.9 months (SD ± 5.5 months). The sample was divided into two groups: the first included patients with delayed speech development (n = 98), the second included children with normal speech development (n = 98). Speech status was assessed using a questionnaire to determine the speech development of a child aged 18 to 36 months (Language Development Survey). In assessing the risk factors for the occurrence of speech development delay, the “Anamnestic Card of the child” was used. To create a neural network that predicts speech delay in children under one year old, a model was developed and trained using the Keras library for the Python 3.0 programming language.Results: the analysis of the accuracy of the neural network showed a high result — 89% of the cases during the training of the model were identified correctly. At the same time, the sensitivity of the model on the test sample was 100%, and the specificity was 90%.Conclusions: the developed method can be used to create a tool for predicting speech development delay in children up to 3 years of age, which will allow for differentiated therapeutic and preventive measures that contribute to the harmonious development of the child.

Epileptic encephalopathy caused by 1p36 deletion: literature review and case series

1p36 deletion syndrome (OMIM: 607872) is an autosomal dominant disease caused by a terminal deletion of the short arm of chromosome 1, characterized by specific craniofacial dysmorphism, delayed speech development and epilepsy. The severity of epilepsy is related to the size of the mutation.Objective: to study the clinical and electroencephalographic picture of the disease.We have analyzed 3 cases (male patients from 2 to 6 years old), including anamnesis of life and disease, electroencephalography data in dynamics and genetic analysis data.All three patients are united by a combination of epilepsy, mental retardation and cerebral palsy-like movement disorders. The epilepsy manifestations varied from severe with absolutely pharmacoresistant epileptic spasms (cases 1 and 2) to mild course with febrile seizures only (case 3). This is probably due to the presence of a shorter mutation in patient 3. Cases 1 and 2 had epileptic encephalopathy, epilepsy with continuing epileptiform discharges on the EEG and a gross delay in speech and mental development. These patients could not speak and not understand the speech addressed, do not follow instructions. Patient 3’ self-care and play activities are developed by age, speech understanding is fully formed, but there is a complete absence of expressive speech.1p36 deletion syndrome is a developmental and epileptic encephalopathy.

Small number enumeration processes of deaf or hard-of-hearing students: A study using eye tracking and artificial intelligence.

Students who are deaf or hard-of-hearing (DHH) often show significant difficulties in learning mathematics. Previous studies have reported that students who are DHH lag several years behind in their mathematical development compared to hearing students. As possible reasons, limited learning opportunities due to a lesser incidental exposure to numerical ideas, delays in language and speech development, and further idiosyncratic difficulties of students who are DHH are discussed; however, early mathematical skills and their role in mathematical difficulties of students who are DHH are not explored sufficiently. In this study, we investigate whether students who are DHH differ from hearing students in their ability to enumerate small sets (1–9)—an ability that is associated with mathematical difficulties and their emergence. Based on a study with N = 63 who are DHH and N = 164 hearing students from third to fifth grade attempting 36 tasks, we used eye tracking, the recording of students' eye movements, to qualitatively investigate student enumeration processes. To reduce the effort of qualitative analysis of around 8,000 student enumeration processes (227 students x 36 tasks), we used Artificial Intelligence, in particular, a clustering algorithm, to identify student enumeration processes from the heatmaps of student gaze distributions. Based on the clustering, we found that gaze distributions of students who are DHH and students with normal hearing differed significantly on a group level, indicating differences in enumeration processes, with students who are DHH using advantageous processes (e.g., enumeration “at a glance”) more often than hearing students. The results indicate that students who are DHH do not lag behind in small number enumeration as compared to hearing students but, rather, appear to perform better than their hearing peers in small number enumeration processes, as well as when conceptual knowledge about the part-whole relationship is involved. Our study suggests that the mathematical difficulties of students who are DHH are not related to difficulties in the small number enumeration, which offers interesting perspectives for further research.

Особливості клінічного дослідження причин затримки мовленнєвого розвитку.

The article contains a study of the causes of speech delay in young children. The symptoms of this disorder, clinical and hardware methods of studying the manifestations of this disorder in children from birth to three years are described. The description of pedagogical manifestations of speech development delay and features of reflection of pathological changes in the structure and functioning of the brain and its trunks is given. Examples of clinical description of pathological symptoms on echoencephalogram, neurosonographic and Doppler examination are given. The causes of speech developmental delay, which include cerebral hypoxia / ischemia, CNS birth trauma, CNS infections, systemic dysmetabolic and toxic-metabolic disorders, are highlighted. The connection between the manifestations of speech developmental delay and the data of X-ray examination of disorders of the integrity and functionality of the cervical spine has been studied. Neurosonographic data confirm problems with harmonious blood supply and maintenance of typical cerebrospinal fluid dynamics in the vessels and ventricles of the brain. The study presents the results of deciphering the results of echoencephalography in relation to the passage of waves of different frequencies through the structures of the brain, identified pathological conditions accompanied by non-normative indicators of frequency and changes in the amplitude of the waves. The reactions of children to auditory stimuli that accompanied the study with the help of audiometry and echoencephalography were studied, and the features of subcortical evoked potentials in the dominant and nondominant hemispheres were determined

Comprehensive assessment of the speech development of children conceived by IVF

Introduction. The high frequency of the use of assisted reproductive technologies and the inconsistency of information about the parameters of the cognitive development of IVF children determined the formulation of the research problem.The purpose of the work is to assess the originality of the speech development of children and adolescents conceived using the IVF procedure. The age of the children at the time of the survey was from 5 to 15 years.Methods and materials. A sample of 51 children (29 boys), mean age (7.9±2.8) years, 14 children had psychiatric diagnoses (ASD, mental retardation, etc.). Research methods: speech therapy assessment of speech development, neuropsychological diagnostics according to L.S. Tsvetkova, WICS, descriptive statistics, correlation analysis.Results. 41% of children had mild variants of speech development delay under 3 years old, 59 % of children had normal speech development. With age, the frequency of detected deviations in speech development decreases, so that in older age group (from 11 to 15 years old), 85 % have normotypical development of speech. Correlation analysis showed the originality of the correlations of the parameters of speech development, neuropsychological assessment, and scores on Wechsler subtests.Conclusions. An unambiguous conclusion about the violation of speech development in children conceived by IVF cannot be drawn, however, in the presence of mental pathology and taking into account the age of the mother and the number of ART procedures, attention should be paid to the provision of speech therapy and neuropsychological correction from an early age.

Proton magnetic resonance spectroscopy in children with delayed mental and speech development associated with focal temporal lobe epilepsy

Background. The delays in mental and speech development are caused by epilepsy, and a special place among the forms of which is focal temporal epilepsy. The study of biomarkers of the considered pathological condition using proton magnetic resonance spectroscopy as indicators amenable to objective assessment and measurement determines the practical relevance of this work.
 Aim. The aim of the study was to determine the role and place of proton magnetic resonance spectroscopy in clinical practice in children with mental and speech retardation associated with temporal lobe epilepsy.
 Materials and methods. 37 children aged 2 to 10 years were studied. Of these, 15 children with a diagnosis of mental and speech development delay, structural focal temporal epilepsy were included in the first comparison group. The second comparison group consisted of 12 children without CNS pathology undergoing 1H-MRI examination to exclude somatic diseases. The third comparison group consisted of 10 children with structural focal temporal epilepsy, without mental and speech development delay.
 Discussion. Multivoxel proton magnetic resonance spectroscopy (method PRESS) was used to determine the concentration of neurometabolites in the brain tissues of patients. In patients with mental and speech development delay associated with temporal epilepsy, a decrease in the ratio of NAA/Cr concentrations (p 0.05) was revealed in the postcentral gyrus on the right, temporal lobe on the right and hippocampus and inner capsule on both sides, due to a decrease in the concentration of N-acetylaspartate; an increase in the ratio of Cho/Cr concentrations (p 0.05) in the prefrontal cortex, postcentral gyrus and inner capsule on both sides, due to an increase in the concentration of choline. Two patients also showed lipid peaks on the lesion side when compared with EEG data.
 Conclusions. The revealed metabolic changes in patients with delayed mental and speech development associated with temporal lobe epilepsy may be useful as an additional method of differential diagnosis with other forms of mental and speech development delay.

Varieties of Comorbid Disorders in Children with Mental Retardation

The subject of the study is comorbid disorders of children with mental retardation. The object of the study is the frequency of comorbid disorders of the children with mental retardation. Using a retrospective analysis of medical records, the authors examine in detail the neuropsychiatric manifestations and behavioral stereotypes that frequently occur in the study sample of children. These behavioral stereotypes or comorbid disorders were noted by parents or health care professionals who interacted with the children. The total sample included 1,000 preschool and young children (from 1.5 to 7 years old) with various neuropsychiatric speech diagnoses - delayed speech development, autism spectrum disorders, delayed psycho speech development, and other unspecified speech diagnoses. The main finding of this study is that a list of the most common comorbid disorders was compiled. Using this list of the most common behavioral disorders, it is possible to make a screening assessment of mental development and identify the degree of its delay on the basis of the formed behavioral and speech patterns. This will help specialists (psychologists, speech therapists, defectologists and neuropsychologists) working with children to provide them with the necessary assistance in a timely manner. The scientific novelty of the study lies in the fact that previously no comprehensive list of the most common behavioral disorders of the children with mental retardation was compiled. This list made it possible to differentiate the primary diagnosed child into one or another group according to the belonging to the diagnosis, with subsequent more thorough verification of the diagnosis.

West syndrome in patients with Kabuki syndrome (literature review and case report)

Kabuki syndrome (KS) is a rare genetic disorder that has facial phenotypic descriptors, retarded growth, various malformations and different degrees of intellectual disability. Objective: to study the characteristic features of KS comorbid with West syndrome according to literature review and data collection together with KS described clinically, and treatment success rates by the clinical case study research. There was conducting literature review on the topic in the databases OMIM, PubMed, Scopus, and e-library. The articles describing cases of epilepsy in patients with KS were analyzed. We conducted our own observation of KS in the male patient with epilepsy and West syndrome in a patient with KS was analyzed by the clinical case study research. Kabuki syndrome comorbid with West syndrome increases neurological deficits and leads to the formation of a marked delay in mental and speech development and psychomotor development retardation. Peculiarities of the treatment of KS comorbid with West syndrome are the lack of efficacy of antiepileptic drugs, and the very visible effectiveness of the ketogenic diet, together with an atypical response to hormone replacement therapy in the form of distinct positive dynamics – a clinically meaningful reduction in seizure frequency along with elevated liver enzymes.

Small Interstitial Deletion at Chromosome 12q21.33q22 in an Individual with Pronounced Delay in Speech Development

Small Interstitial Deletion at Chromosome 12q21.33q22 in an Individual with Pronounced Delay in Speech Development

Motor proficiency of children with developmental speech and language disorder and typically developing children aged 4–7 years: A comparative cross-sectional study

Background: Developmental speech and language disorder (DSLD) is characterized by delay in speech and language development in the absence of mental or physical handicap, hearing loss, emotional disorder, or environmental deprivation. Many nonlinguistic factors contribute to the expression of DSLD, one of them is motor proficiency. Some problems with motor proficiency were observed in children with DSLD when they were compared with typically developing children (TDC). Objective: The objective of the study was to assess the performance of DSLD children for motor proficiency using the Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2) and compare it with TDC. Study Design: A comparative, noninterventional, cross-sectional study. Methods: The study included 30 children with DSLD and 30 TDC aged 4–7 years. The study protocol was approved by the Institute Ethical Committee (ECARP/2017/21). A written informed consent form was signed by parents. All composites of BOT-2 were administered on both groups (fine manual control, manual coordination, body coordination, strength and agility). Scores obtained were compared between two groups for total motor composite as well as each subtest. Results: There was a significant difference between the performance of DSLD children and TDC on all the four composites, namely Fine Manual Control, Manual Coordination, Body Coordination, and Strength and Agility of BOT-2. Total motor composite score of DSLD children was significantly different from the scores of TDC at P = 0.000. Conclusion: Motor proficiency is significantly affected in children with DSLD as compared to TDC.

Speech development in children of preschool age with arthrogryposis multiplex congenital with upper limb deformities

BACKGROUND: The difficulties or gross disturbance in motor development, which are diagnosed in children at an early age, are one of the prognostic markers of further problems in their speech development.
 AIM: This study aimed to determine the speech development of children with arthrogryposis multiplex congenita with upper limb deformities.
 MATERIALS AND METHODS: Speech examination was conducted in 21 children with arthrogryposis multiplex congenita preschool age (average age: 5.16 1.49 years) from 2020 to 2021. Patients were divided into 2 groups: group 1 (10 people) with children of younger and middle preschool age (average age 3.81 0.63 years) and group 2 (11 people) with children of older and preparatory preschool age (average age 6.39 0.78 years). The speech examination results were exposed to statistical analysis.
 RESULTS: The majority of children with arthrogryposis multiplex congenita had speech pathology (90.5%), whereas general speech underdevelopment dominated over speech development delay (78.9% and 21.1%, respectively). A high frequency of perinatal hypoxic-ischemic encephalopathy in children with arthrogryposis multiplex congenita (80.9%), a complicated perinatal anamnesis (57.1%), and a delay in early motor or speech development (100% and 52.4%, respectively) links with speech disorder development in the future. Patients with arthrogryposis have a large percentage of congenital pathology of the articulatory apparatus structure (57.1%). Of the children, 76.2% were with a total form of arthrogryposis multiplex congenita, whereas 23.8% with an isolated upper extremity lesion. No statistically significant differences were determined in the form of speech pathology between patients with various forms of arthrogryposis multiplex congenita. Children of the first age group had speech disorders in 90% of cases, whereas 90.9% in group 2. Based on the form of speech pathology, patients with general speech underdevelopment and speech development delay were determined in group 1 (55.6% and 44.4%, respectively), whereas children with general speech underdevelopment in group 2 (100%). In the clinical form of speech pathology, dysarthria prevailed in children of both age groups (80%).
 CONCLUSIONS: Children with arthrogryposis multiplex congenita with upper limb deformities have a high incidence of speech disorders. Early speech examination and speech therapy eliminated all detected disturbances.

Early diagnosis of mucopolysaccharidosis type III (Sanfilippo syndrome) in the practice of a pediatrician

Mucopolysaccharidosis (MPS) type III (Sanfilippo syndrome) is a lysosomal storage disease inherited in an autosomal recessive manner, it is characterized by the accumulation of heparan sulfate in the cells of the body, which leads to the development of multiple organ failure. It occurs with a frequency of 1: 70 thousand newborns. There are 4 subtypes of the disease: A, B, C, D. Cognitive and neurological disorders are the earliest symptoms of the disease. Delay (loss) of speech development, regression of acquired skills, hyperreactivity, autistic character traits, mental retardation, sleep disturbance, epilepsy are noted; aggressive behavior is formed, the ability to move is impaired, hepatomegaly appears. There are observed the violations of other organs and systems – the organ of vision, bone, respiratory, cardiovascular systems, ENT organs, dental problems. Clinically, the subtypes of mucopolysaccharidosis III are practically indistinguishable. The average age at diagnosis is 2–6 years. Diagnostic search includes qualitative and quantitative determination of glycosaminoglycans in urine. It should be remembered that with mild variants of the disease, these indicators may be within the normal range. In the future, it is necessary to assess the activity of the corresponding enzymes in leukocytes, plasma or serum, in skin fibroblasts. Genetic testing is then performed to identify the mutation of the corresponding defective gene. Differential diagnosis should be carried out with other types of mucopolysaccharidosis, mucolipidosis, gangliosidosis, multiple sulfatase deficiency, some rheumatoid diseases.

Eye-tracking study of joint attention deficits in pre-school age

The article investigates joint attention deficits in various forms of atypical development using eye movement recording. Preschoolers aged 5-7 years from different clinical groups participated in the study: typically developing (n = 20), with mental retardation (ICD-10 class F83) (n = 20), preschoolers with delayed speech development (ICD-10 class R47) (n = 20), with hearing impairment (sensorineural hearing loss, ICD-10 class H90) (n = 10) and with visual impairment (amblyopia and strabismus, IBC-10 class H53) (n = 20). Contrasting group analyses allowed us to identify both specific and universal manifestations of joint attention deficit symptoms in the different forms of atypical development. Gaze tracking was used to analyze fixation duration and frequency, fixation distribution, areas of interest, and to identify markers of joint attention deficits that interfere with the child's productive interaction with an adult. Potential mechanisms of atypical joint attention are described, including atypical direction of gaze, changes in the dynamics of the operative visual field, duration of visual concentration, and accuracy in fixing the object’s elements. It is shown that fixation time in joint attention episodes can be regarded as a prognostic marker of joint attention disorders: joint attention is associated not only with spatial characteristics of areas of interest, but also with fixation duration on the object (decrease/increase in fixation duration).

Risk factors for delayed speech development in children of early and preschool age

Speech is the most critical component of the neuropsychic development of a child. Over the past decade, an increase in the prevalence of delayed speech development (DSD) in children has been recorded worldwide. Timely diagnosis and correction of DSD at the early stages can lead to good results and minor violations of speech development in the future. Objective. To execute a comparative analysis of risk factors and the leading causes of the DSD development in children of early and preschool age in the Belgorod region from 2019 to 2021. Materials and methods. The analysis of 165 medical records of children examined and treated at the Belgorod Medical Center for the period from 2019 to 2021 was carried out. Results. DSD was found to be more common in children aged 1.5 to 3 years (79.5%), much less common in children over the age of 4 years (6.6%).DSD in boys (69.7%) occurs more than two times more common than girls (30.9%). The average age of mothers of DSD children ranged from 30 to 35 years. More than 50% of all DSD children are premature babies. All mothers of the examined patients had a complicated pregnancy and delivery in their history. Children living in the city (62.5%) had a 25% higher probability of DSD occurrence than children from rural areas (37.5%). According to the results of the study, lesions of the visual organs, residual and perinatal lesions of the central nervous system were the most common forms of pathology in DSD children. Conclusion. It is necessary to improve the early diagnosis and prevention of the DSD in children. Early detection of deviations in the child’s speech development will allow timely drug therapy and comprehensive systematic corrective work.

Mutation in the CREBBP Gene in the Girl with Toe Walking Syndrome: Clinical Case

Baclground. Pathogenic variants of the CREBBP gene have been revealed in patients with Rubinstein-Taybi and Menke-Hennekam syndromes, however, the toe walking symptom was not mentioned in these pathologies.Clinical Case Description. The pathogenic nucleotide variant c.5600G>A in heterozygous state in the CREBBP gene was revealed in our 9-year-old female patient with refractory toe walking and developmental speech delay. There were no abnormalities typical for Rubinstein-Taybi syndrome, but there were several signs of Menke-Hennekam syndrome.Conclusion. The genetic anomaly associated with toe walking is described. This observation allows us to critically relate to the hypothesis about the idiopathic genesis of this form of gait disorder at the absence of obvious neurological or orthopedic causes of its development.

Wide Fontanels, Delayed Speech Development and Hoarse Voice as Useful Signs in the Diagnosis of KBG Syndrome: A Clinical Description of 23 Cases with Pathogenic Variants Involving the ANKRD11 Gene or Submicroscopic Chromosomal Rearrangements of 16q24.3.

KBG syndrome is a neurodevelopmental autosomal dominant disorder characterized by short stature, macrodontia, developmental delay, behavioral problems, speech delay and delayed closing of fontanels. Most patients with KBG syndrome are found to have a mutation in the ANKRD11 gene or a chromosomal rearrangement involving this gene. We hereby present clinical evaluations of 23 patients aged 4 months to 26 years manifesting clinical features of KBG syndrome. Mutation analysis in the patients was performed using panel or exome sequencing and array CGH. Besides possessing dysmorphic features typical of the KBG syndrome, nearly all patients had psychomotor hyperactivity (86%), 81% had delayed speech, 61% had poor weight gain, 56% had delayed closure of fontanel and 56% had a hoarse voice. Macrodontia and a height range of −1 SDs to −2 SDs were noted in about half of the patients; only two patients presented with short stature below −3 SDs. The fact that wide, delayed closing fontanels were observed in more than half of our patients with KBG syndrome confirms the role of the ANKRD11 gene in skull formation and suture fusion. This clinical feature could be key to the diagnosis of KBG syndrome, especially in young children. Hoarse voice is a previously undescribed phenotype of KBG syndrome and could further reinforce clinical diagnosis.