Early Psychomotor Development Research Articles

Early psychomotor development and growth hormone therapy in children with Prader-Willi syndrome: a review.

Prader-Willi syndrome (PWS) is a rare genetic disorder caused by the loss of imprinted gene expression on the paternal chromosome 15q11-q13. PWS is characterized by varying degrees of early psychomotor developmental deficits, primarily in cognition, language, and motor development. This review summarizes the early mental cognitive development, language development, and motor development in patients with PWS, compares the correlation of genotype with phenotype, and provides an update regarding the effects and concerns related to potential main side effects of treatment with recombinant human growth hormone on early psycho-cognitive and motor function development along with the linear growth and body composition of children with PWS.Conclusion: Early psychomotor development is strongly correlated with the prognosis of patients with PWS; moreover, current studies support that the initiation of interventions at an early age can exert significant beneficial effects on enhancing the cognitive and linguistic development of patients with PWS and allow them to "catch up" with motor development. What is Known: • Prader-Willi syndrome is a rare genetic disorder characterized by multisystem damage, andchildren with Prader-Willi syndrome are typically characterized by early developmental delays, specifically in the areas of cognitive and motor development. •Recombinant human growth hormone therapy is the only medical treatment approved for Prader-Willi syndrome. What is New: •Extensive presentation of psycho-cognitive and motor development features and genotype-phenotype correlation in children with Prader-Willi syndrome. • The effects of growth hormone on early psychomotor development in children with Prader-Willi syndrome were thoroughly reviewed, including their short- and long-term outcomes and any associated adverse effects.

Uloga gena modifikatora na klinički tok Dišenove mišićne distrofije

Duchenne muscular dystrophy is the most common inherited muscle disease in childhood, which has a progressive clinical course with a fatal outcome that most often occurs between the second and fourth decade of life. The disease is inherited X-linked, recessively, and in two-thirds of patients, it is transmitted from the mother, while in the remaining third of patients, it is a de novo mutation. Mutations in the dystrophin gene (DMD gene) such as deletions, duplications and small mutations can be found throughout the entire length of the gene. The disease begins between the third and fifth year of life, and the initial muscle weaknesses are clinically manifested as slower running, difficulty climbing stairs or difficulty getting up from squats. Sometimes, accidentally discovered, elevated keratin kinase values or delayed early psychomotor development milestones in a child with hypertrophic calves can initiate a diagnostic procedure in the direction of Duchenne muscular dystrophy. The disease usually has a uniform clinical course and implies a clear time sequence of events. Muscle weakness leads to loss of ambulation, then the function of the upper extremities, to complete immobility, with the evolution of dilated cardiomyopathy and respiratory insufficiency, which are the main causes of death. Certain patients show deviations from the above in terms of longer functionality and later loss of independent ambulation, later cardiomyopathy and respiratory insufficiency and vice versa. It is believed that in addition to the application of modern standards of care and treatment of patients, the clinical course is influenced by genes independent of the causal DMD gene, which affects processes in dystrophic muscle, primarily inflammation, fibrosis and fatty infiltration, through specific signaling pathways. So far, six genes have been described whose variants modify the course of Duchenne muscular dystrophy. The secreted phosphoprotein 1 (SPP1) is the first described gene whose G allele in the variant rs28357094 is associated with an earlier age of gait loss. In addition, variants in the genes described are LTBP4 (latent transforming growth factor-b binding protein 4), CD40, ACTN3 (actinin 3), THBS1 (thrombospondin 1) and TCTEX1D1 (Tctex1 domain containing 1). The aim of this paper is to present already-known genes that modify Duchenne muscular dystrophy and their influence on the clinical course of the disease.

Changes in the Cerebrospinal Fluid and Plasma Lipidome in Patients with Rett Syndrome

Rett syndrome (RTT) is defined as a rare disease caused by mutations of the methyl-CpG binding protein 2 (MECP2). It is one of the most common causes of genetic mental retardation in girls, characterized by normal early psychomotor development, followed by severe neurologic regression. Hitherto, RTT lacks a specific biomarker, but altered lipid homeostasis has been found in RTT model mice as well as in RTT patients. We performed LC-MS/MS lipidomics analysis to investigate the cerebrospinal fluid (CSF) and plasma composition of patients with RTT for biochemical variations compared to healthy controls. In all seven RTT patients, we found decreased CSF cholesterol levels compared to age-matched controls (n = 13), whereas plasma cholesterol levels were within the normal range in all 13 RTT patients compared to 18 controls. Levels of phospholipid (PL) and sphingomyelin (SM) species were decreased in CSF of RTT patients, whereas the lipidomics profile of plasma samples was unaltered in RTT patients compared to healthy controls. This study shows that the CSF lipidomics profile is altered in RTT, which is the basis for future (functional) studies to validate selected lipid species as CSF biomarkers for RTT.

The associations of prenatal exposure to dioxins and polychlorinated biphenyls with neurodevelopment at 6 Months of age: Multi-pollutant approaches

BackgroundPrenatal exposure to persistent organic pollutants, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DL-PCBs), and nondioxin-like PCBs (NDL-PCBs), has been hypothesized to have a detrimental impact on neurodevelopment. However, the association of prenatal exposure to a dioxin and PCB mixture with neurodevelopment remains largely inconclusive partly because these chemical levels are correlated. ObjectivesWe aimed to elucidate the association of in utero exposure to a mixture of dioxins and PCBs with neurodevelopment measured at 6 months of age by applying multipollutant methods. MethodsA total of 514 pregnant women were recruited between July 2002 and October 2005 in the Sapporo cohort, Hokkaido Study on Environment and Children's Health. The concentrations of individual dioxin and PCB isomers were assessed in maternal peripheral blood during pregnancy. The mental and psychomotor development of the study participants' infants was evaluated using the Bayley Scales of Infant Development-2nd Edition (n = 259). To determine both the joint and individual associations of prenatal exposure to a dioxin and PCB mixture with infant neurodevelopment, Bayesian kernel machine regression (BKMR) and quantile-based g-computation were employed. ResultsSuggestive inverse associations were observed between in utero exposure to a dioxin and PCB mixture and infant psychomotor development in both the BKMR and quantile g-computation models. In contrast, we found no association of a dioxin and PCB mixture with mental development. When group-specific posterior inclusion probabilities were estimated, BKMR suggested prenatal exposure to mono-ortho PCBs as the more important contributing factors to early psychomotor development compared with the other dioxin or PCB groups. No evidence of nonlinear exposure-outcome relationships or interactions among the chemical mixtures was detected. ConclusionsApplying the two complementary statistical methods for chemical mixture analysis, we demonstrated limited evidence of inverse associations of prenatal exposure to dioxins and PCBs with infant psychomotor development.

Assessment of the initial period of schizotypal disorder in childhood

To identify developmental features, the presence of hereditary burden, social adaptation, the structure of early psychopathological disorders in pediatric patients with schizotypal disorder (STD) and their relationship with the age of manifestation and the clinical structure of the disease. The study included 150 patients aged 7 to 16 years with a diagnosis of SD, of which 48 were female and 102 were male. Based on the age of onset of the first stable psychopathological disorders, at the stage preceding the diagnosis of SD, 5 groups of patients were identified: up to 3 years (n=38), from 4 to 6 years (n=36), from 7 to 10 years (n=15), 11-13 (n=41), 14-16 years old (n=20). The study used clinical-psychopathological, clinical-catamnestic, with a retrospective analysis, neurological, pathopsychological, psychometric and statistical research methods. A high frequency of deviations from normative parameters in early psychomotor development was found in 99 (65%) patients with STD. Mental retardation was observed in 23 (15%) patients, dissociation in mental development was detected in a significant number of patients - 62 (41%). At the same time, the most significantly more frequent and pronounced were violations in the two youngest groups with the onset of psychopathological disorders up to 6 years. In these groups, there was also more often a deficit in three areas at once - emotional, motivational and volitional (38%) compared with the 4th group (13%). In groups 1 and 2, a deficit in intellectual development was also characteristic, which was reflected in academic indicators. High performance in the primary grades was observed in 16% of patients in the 1st group versus 60% in the 5th, and poor performance was found in 37% in the 1st group and only 5% in the 5th. The relationship of clinical variants of STD with the selected groups was revealed. The diagnosis of schizotypal personality disorder was significantly more often (66%) diagnosed in patients from group 1 compared with groups 3 and 5. In group 2, this diagnosis was established in a third of cases. The diagnosis of the psychopathic variant of STD was predominant in patients with the onset of the disorder between 7 and 13 years of age. The neurosis-like variant had a clear tendency to become more frequent with older age, reaching statistically significant differences in group 5 compared to group 1. The age of onset and duration of persistence of psychopathological disorders determines the level of negative changes that have formed at the stage of the disease preceding the onset of distinct clinical symptoms of STD. Age at onset determines the predominant positive disorder.

The Associations of Prenatal Exposure to Dioxins and Dioxin-Like Polychlorinated Biphenyls with Neurodevelopment at 6 Months of Age: Multi-pollutant Approaches

BACKGROUND AND AIM: Prenatal exposure to endocrine disrupting chemicals, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs), has been hypothesized to have detrimental impact on neurodevelopment. However, the effect of prenatal exposure to dioxin and DL-PCB mixtures on neurodevelopment remains largely inconclusive. Therefore, we aimed to elucidate the associations of in utero exposure to a dioxin and DL-PCB mixture with infant neurodevelopment by applying novel multi-pollutant methods. METHODS: The concentrations of individual dioxin and DL-PCB isomers were measured in maternal peripheral blood during pregnancy in the Sapporo cohort, Hokkaido Study on Environment and Children’s Health. The mental and psychomotor development of the study participants’ six-month-old infants were assessed using the Bayley Scales of Infant Development-2nd Edition (n=210). To determine both the joint and individual associations of prenatal exposure to dioxin and DL-PCB mixtures with infant neurodevelopment, Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation models were performed. RESULTS:Suggestive, but not significant, inverse associations were observed between prenatal exposure to a dioxin and DL-PCB mixture, and infant psychomotor development in the both BKMR and quantile g-computation models. In contrast, we found no association of dioxin and DL-PCB mixtures with mental development. These mixture methods consistently indicated 2,3,7,8-TCDD and 23'44'55'-HxCB(#167) as the most influential dioxin and DL-PCB congener on mental and psychomotor development, respectively. When group-specific posterior inclusion probabilities were evaluated, BKMR revealed in utero exposure to PCDFs and mono-ortho DL-PCBs as the more important contributing factors to early mental and psychomotor development, respectively, compared with the other dioxin or DL-PCB groups. No evidence of non-linear relationships or interactions among the chemical mixtures was detected. CONCLUSIONS:Employing the novel statistical methods for chemical mixture analysis, we demonstrated limited evidence of inverse associations of prenatal exposure to dioxins and DL-PCBs with infant psychomotor development, but not with mental development. KEYWORDS: Chemical mixtures, Dioxins, Polychlorinated biphenyls, Neurological development, Bayesian Kernel Machine Regression, Quantile g-computation

Predicting the developmental outcomes of very premature infants via ultrasound classification: A CONSORT - clinical study.

Objective:This study aimed to assess the accuracy of ultrasonic grading in determining brain injury in very premature infants and analyze the affecting factors of these neonatal morbidity and mortality, and to investigate the relationship between serial cranial ultrasound (cUS) classification and Mental Developmental Index (MDI)/Psychomotor Developmental Index (PDI) in premature infants.Methods:A total of 129 very preterm infants (Gestational Age ≤ 28 weeks) were subjected to serial cUS until 6 months or older and classified into 3 degrees in accordance with classification standards. The MDI and PDI (Bayley test) of the infants were measured until the infants reached the age of 24 months or older. The consistency between Term Equivalent Age (TEA)-cUS and TEA- magnetic resonance imaging (MRI) was calculated. Ordinal regression was performed to analyze the relationship among severe disease, early cUS classifications, psychomotor and mental development, and death. Operating characteristic curve were used to analyze the relationship between serial cUS grades and MDI/PDI scores.Results:The mortality and survival rates of 129 very preterm infants were 32.8% and 67.3%, respectively. Among the 86 surviving infants, 20.9% developed mild cerebral palsy (CP) and 5.8% to 6.9% developed severe CP. The consistency between TEA-cUS and TEA-MRI was 88%. Grades 2 and 3 at first ultrasound were associated with adverse mental (OR = 3.2, OR = 3.78) and motor (OR = 2.25, OR = 2.59) development. cUS classification demonstrated high sensitivity (79%–96%). Among all cUS classifications, the specificity of the first cUS was the lowest and that of TEA-cUS was the highest (57% for PDI and 48% for MDI).Conclusions:Moderate and severe brain injury at first ultrasound is the most important factor affecting the survival rate and brain development of very premature infants. The cUS classification had high sensitivity and high specificity for the prediction of CP, especially in TEA-cUS.

Early signs of autism in infants whose mothers suffered from a threatened preterm labour: a 30-month prospective follow-up study.

Infants born after a threatened preterm labour (TPL infants) are at high risk of autism spectrum disorder (ASD). Studying this population may provide insight on the pathophysiological underpinnings of this condition. This study aimed to (i) ascertain the presence and autistic symptom load in TPL infants aged age 30months relative to non-TPL infants, regardless of preterm birth; (ii) explore the association between early (at 6months) psychomotor development and temperament features with the autistic symptom load of TPL infants at age 30months and (iii) examine the association among perinatal risk factors for ASD development with the autistic symptom load of TPL infants at age 30months. A group of 111 mother-infant pairs recruited at TPL diagnosis and a group of 47 healthy mother-infant controls completed the follow-up. Irrespective of preterm birth, TPL infants showed higher autistic symptom load at age 30months than non-TPL infants. TPL infants presented poorer communication and problem-solving skills, reduced smiling and laughter, and greater vocal reactivity at age 6months, predicting higher autistic symptom load at age 30months. Higher levels of anxiety symptoms in TPL mothers after a TPL diagnosis also predicted higher autistic symptom load for the infants at age 30months. These results suggest that TPL infants may be an undescribed cluster, with features that differentiate them from other "at-risk" populations. These findings support the need for routine assessment of TPL infants and screening of anxiety symptoms in mothers.

Treatment of velopharingeal insuffitiency with turn over mucoperiosteal palatinal flap in a patient with DiGeorge syndrome

Introduction. DiGeorge syndrome (velocardiofacial syndrome) occurs in about 1 in 4,000 people. It is characterized by incomplete gene penetration, due to which there is significant variability in the clinical picture in different patients. The paper describes the successful application of an inverted mucoperiosteal flap of the palate in a nine-year-old girl with DiGeorge syndrome who had pronounced velopharyngeal insufficiency (VPI). Case report. The girl was the first-born child from a normal pregnancy and a normal birth with a normal early psychomotor development. During breastfeeding, milk was occasionally returned to the nose, and later deviations from normal speech (incomprehensible and nasal speech) were noticed. At the age of 4, detailed genetic testing was performed and a microdeletion of 22q11 chromosome was found. Also, a submucosal cleft palate was established, and magnetic resonance angiography of the head and neck revealed an abnormal position of the left internal carotid artery (ICA) that extended submucosally to the central axis of the posterior wall of the pharynx. Then, the submucosal cleft palate was surgically resolved in other clinical center, but without speech improvement. Pharyngoplasty was not performed due to the risk of serious post-operative complications. It was explained to the parents that speech recovery will not be satisfactory without surgical treatment of VPI. At the age of 9, the girl was admitted to the Clinic for Plastic and Reconstructive Surgery and Burns of the Military Medical Academy in Belgrade for surgical treatment of VPI. Taking into account the potential risks of certain surgical methods, it was decided to perform intravelar veloplasty according to Furlow. Since it was intraoperatively found that the soft palate is too short and that this procedure cannot provide its sufficient length, the mucoperiosteal flap was lifted from the palate to the palatal aponeuroses on the posterior edges of the palatine bones leaving their oral surfaces exposed. The mucoperiosteal flap raised in this way could not also provide the required length of the soft palate only by retroposition. However, its length is 160% of the soft palate axis length, which was enough to turn over the front of the flap towards the pharynx of the soft palate to reach its posterior wall. The raised mucoperiosteal palatal flap has no muscles, so its motility was achieved by the fact that along the edges of the existing short and mobile palate, the flap was fixed to the existing palate and uvula. This provided the anatomical preconditions for speech recovery, shown during the one-year post-operative follow-up of the child. Exposed palatine bones and short palate was covered by mucosal tissue, without cystic formations. Conclusion. The mucoperiosteal palatal flap can be easily, successfully and maximally safely applied in the resolution of VPI in patients with DiGeorge syndrome where there is an aberrant submucosal position of the ICA. This flap could be a ?flap of choice? for such patients with atopic position of the ISA, too.

Desarrollo psicomotor en la infancia temprana y funcionalidad familiar

Se investigó el desarrollo psicomotor temprano y si existían diferencias significativas en las diversas áreas de este desarrollo según la funcionalidad familiar (cohesión y adaptabilidad familiar) desde la percepción materna. Se trabajó con un diseño no experimental de alcance descriptivo. La muestra estuvo compuesta por 32 diadas madre-hijo de entre 12 y 27 meses de edad. Se administró el Instrumento de Observación del Desarrollo Infantil (IODI), la Prueba Nacional de Pesquisa (PRUNAPE) y FACES III. Se encontraron diversas diferencias significativas entre tipo de cohesión-adaptabilidad familiar y áreas de la PRUNAPE (p<.05) y del IODI (p<.05). Se observó un desarrollo infantil temprano más favorable en las áreas personal social, lenguaje y socioemocional, en aquellas familias conectadas y flexibles.

Effects of Massage Therapy on the Development of Babies Born with Down Syndrome.

Objective To determine the short-term effects of infant massage on the development of Down syndrome babies. Materials and Methods The study compared two groups (intervention and control), each with 16 babies with Down syndrome between 4 and 8 months old. The variables developmental age and developmental quotient were measured at two distinct time points, at pretest and after 5 weeks, using the Brunet-Lézine Early Childhood Psychomotor Development revised scale. This scale measures the variables of age and development quotient in a partial way (motor, visual-motor coordination, language, and social development) and in a global way. The experimental group received infant massage, applied by the parents, during these 5 weeks, every day for at least 10 minutes. The massage protocol was based on the methodology created by Vimala McClure. The control group received it after 5 weeks. Results All developmental variables were improved in the experimental group but not in the control group. There were significant differences in developmental age between the two groups, and this outcome was better in the experimental group (p < 0.001). The 2-by-2 mixed-model analysis of variance indicates a statistically significant group-by-time interaction for all development quotients, both partial and global (p < 0.001), which was significantly higher in the experimental group than in the control group. Conclusion Infant massage therapy improves the development of babies with Down syndrome in the short term.

Residential exposure to green space and early childhood neurodevelopment

BackgroundA few studies reported that exposure to high levels of residential surrounding green spaces was associated with better cognitive development in primary school children. However, no studies have been conducted to examine such association in early childhood. ObjectivesWe investigated the association between residential exposure to green space and early childhood neurodevelopment, and further explored the mediation effects of traffic-related air pollution and maternal physical activity on this association. MethodsWe enrolled 1312 pregnant women between January 2012 and October 2015 and their children were followed up until an age of 2 years. We measured residential exposure to green space by calculating averaged normalized difference vegetation index (NDVI) within a 300 meter buffer area surrounding residential address at birth. The neurodevelopment, which included mental development index (MDI) and psychomotor development index (PDI), was assessed using Bayley Scales of Infant Development for each child at about 24 months. The associations of residential exposure to NDVI with early childhood MDI score and PDI score were evaluated using multiple linear regression models. The mediation effects of traffic-related air pollution and maternal physical activities on those associations were estimated by causal mediation analyses. ResultsExposure to higher levels of residential surrounding green spaces was associated with increased early childhood PDI score (adjusted changes for one SD increment of NDVI: 3.28 (95% CI: 2.15, 4.41)) and MDI score (adjusted changes for one SD increment of NDVI: 1.97 (95% CI: 0.63, 3.30). These associations were more pronounced in children of mothers whose pre-pregnancy BMI were lower than 24 kg/m2. Further mediation analyses indicated that reduced levels of traffic-related air pollution explained 13.6% to 28.0% of the association between exposure to green space and early childhood PDI score. ConclusionExposure to higher levels of residential surrounding green spaces was associated with better early childhood neurodevelopment. The association between exposure to green space and early childhood psychomotor development might be partly explained by reduced levels of traffic-related air pollution.

Progressive myoclonus epilepsy caused by a gain-of-function KCNA2 mutation

Progressive myoclonus epilepsy caused by a gain-of-function KCNA2 mutation

Association between maternal exposure to major phthalates, heavy metals, and persistent organic pollutants, and the neurodevelopmental performances of their children at 1 to 2 years of age- CHECK cohort study

Exposure of the developing fetus and infants to toxic substances can cause serious lifelong health consequences. Several chemicals have been associated with adverse neurodevelopmental disorders in the early life stages of humans. However, most epidemiological studies have focused on a limited number of chemicals, and hence may exclude important chemicals from consideration or result in conclusions built on associations by chance. In the present study, we investigated the chemical exposure profile of the women, and associated these with the early neurodevelopmental performance of their offspring at 13–24months of age. The chemicals assessed include four phthalates, bisphenol A, three heavy metals, 19 polychlorinated biphenyls (PCBs), 19 organochlorine pesticides, and 19 polybrominated diphenyl ethers, which were measured from urine, whole blood, serum, and/or breastmilk of the pregnant or lactating women. For neurodevelopmental performance, the Bayley Scales of Infant Development-II (BSID-II), Social Maturity Scale (SMS), and Child Behavior Checklist (CBCL) were measured from a total of 140 toddlers. Among the measured chemicals, monoethyl phthalate (MEP) in maternal urine was significantly associated with early mental, psychomotor, and social development. In addition, breast milk di-ethylhexyl phthalate (DEHP) metabolite and blood lead concentrations were inversely associated with mental and psychomotor development indices, respectively. Maternal blood PCB153, heavy metals, and urinary MEP levels were also higher among the children with behavioral problems, as indicated by the CBCL range. Taken together, maternal exposure to several EDCs such as PCBs and DEHP was associated with adverse neurodevelopmental performances among the children aged 1–2years. Confirmation of these association in larger populations, as well as longer-term consequences of such exposure warrant further investigation.

NOTCH2 genetic mutation and acro-osteolysis-the Hajdu-Cheney syndrome.

A 34-year-old male who works professionally as a computer graphic designer was examined. The patient has a positive family history, as similar symptoms have been observed in the father. The gestation and early psychomotor development of the patient were normal. In the second decade of life, a progressive bone disorder occurred, initially in the form of acro-osteolysis within the distal phalanges of the hands and feet. A physical examination showed the following dysmorphic features: dense eyebrows and eyelashes, downward slanting palpebral fissures, a long philtrum, low …

Persistence of primitive reflexes and associated motor problems in healthy preschool children.

IntroductionRetained primitive reflexes can disturb natural development and involve difficulties in social and educational children’s life. They can also impact on psychomotor development. Mature responses in a child’s psychomotor progress can only occur if the central nervous system itself has reached maturity. The process consist the transition made from brain stem reflex response to cortically controlled response. This study define the occurrence of primitive reflexes in healthy 4–6 years old children and analyze the impact of survived primitive reflexes on psychomotor development.Material and methodsThe study involved 35 participants aged 4–6 years healthy preschool children. The study tools were: primitive reflexes tests by Sally Goddard for children and Motor Proficiency – Test (MOT 4–6 test) in 18 tasks.ResultsOver a half (65%) preschool children had survived the primitive reflexes on the residual level. Eleven percent of them had no retained primitive reflexes. According to the psychomotor ability, 9% of the children were in the category of “altered development”, 29% in “delayed development”, 59% in “normal” and 3% in “very good development”. The greater the severity of the reflex, the motor efficiency was lower (p < 0.05).ConclusionsIt seems reasonable to introduce reflexes integration therapy in children’s with low psychomotor skills. Primitive reflexes routinely tested, can contribute to improved early psychomotor development in children with needs, thus preventing many difficulties which children can encounter within their social and school life.

Autism and Early Neurodevelopmental Milestones

Autism spectrum disorder, also referred to in this study as autism, is a neurodevelopmental chronic disease that manifests early in childhood by impairment in social interaction, communication and repetitive behavior. Since there are no specific biomarkers available, the diagnosis is based exclusively on clinical criteria. The purpose of the present study is to determine which are the early psychomotor development or neurodevelopmental milestones that present a significant correlation with the severity of the main symptoms of autism, development quotients, and adaptive function. We performed a retrospective study on a sample of 1572 individuals with a diagnosis of autism that were monitored at Hospital Pediátrico do Centro Hospitalar e Universitário de Coimbra, in the Neurodevelopment and Autism Unit. We analyzed six early psychomotor developmental milestones: age of acquisition of 'walking', 'first words', 'first phrases', 'daytime control of bladder sphincter', 'night-time control of bladder sphincter', and age of first complaints. Afterwards, we divided the sample in three subgroups regarding clinical severity, according to the Childhood Autism Rating Scale, and we analyzed significant differences among each other concerning the six milestones established beforehand. The milestone 'age of first phrases' was, from the six milestones, the one with a stronger correlation with the variables of clinical manifestations of autism, development/intelligence quotients, and adaptive function. In division of the sample into subgroups of clinical severity, it was the most severe that showed later ages of acquisition of the neurodevelopmental milestones and earlier ages of first complaints. This study proves the clinical utility to know the age of achievement of early psychomotor developmental skills, since they act as predictors of clinical severity of autism, cognition, and adaptive function of a wide population with autism. Therefore, this data contribute for prognostic and prediction of autism progression. Taking into account the results of this study, it is strongly recommended to all clinicians who have contact with autistic children, to record the 'age of acquisition of first phrases'.

P109 – 2442: Infantile neuroaxonal dystrophy: A new mutation

Objective Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive neurodegenerative disorder characterised by rapid cognitive and motor regression, axial hypotonia, gait disturbance, limb spasticity, cerebellar signs, and optic atrophy. Although magnetic resonance imaging (MRI) can sometimes contribute towards the diagnosis, the confirmation of INAD is by Pla2G6 gene analysis. Methods A patient is presented with motor retardation, hypotonia and diagnosed as INAD with a new mutation. Results We report a two years old boy who was referred with difficulty in walking and frequent falls. He has started walking and talking at the age of one. He couldn't make two words sentence. He has two siblings of whom one of them had similar findings. He Her early psychomotor development was normal till 1 year of age. From age 1, she stopped making progress and subsequently she developed seizures, mental regression and became bedridden. Her MRI revelaed cerebellar atrophy. She died at the age of six without diagnosis. His other sister was at the age of 16 and her medical history was unremarkable. The parents have a third-degree consanguinity. Neurological examination of our case showed hypotonia and had areflexia. His initial MRI was normal whereas the following MRI after nine months revealed cerebellar vermian hypoplasia. Metabolic screening tests were normal (Tandem mass spectroscopy, very long chain fatty acid, plasma and urine aminoacids, transferin isoelectric focusing for CDG). Electromyography showed motor axonal neuropathy. His visual examination was normal. Molecular analysis of PLA2G6 gene demonstrated a novel homozygous P.G586R (c.1756G>A) mutation. Conclusion Our case indicates that INAD should be kept in mind in the differential diagnosis of patients with hypotonia and psychomotor regression.

OP24 – 2321: FINGORETT – An ongoing phase I clinical study to assess safety and efficacy of oral fingolimod (FTY720) in children with Rett syndrome

Objectives Rett syndrome is a neurodevelopmental disorder characterized by normal early psychomotor development followed by the loss of acquired skills. Phenotypic reversal by activation of MECP2 (see Guy et al. Science 2007) triggered hope towards possible therapeutic options for this disease. BDNF (brain-derived neurotrophic factor) levels were identified to influence disease phenotype in mice (Chang et al. Neuron 2006). FTY720 (fingolimod) is an oral modulator of S1P (sphingosine-1 phosphate) receptors. It increases BDNF levels and improved symptoms of a mouse model of Rett syndrome (Deogracias et al. Proc Natl Acad Sci USA 2012). Our study has been designed to assess safety of oral FTY720 and to study some outcome measures in order to evaluate a possible efficacy of FTY720 in children with Rett Syndrome. Methods 6 children with Rett-Syndrome (confirmed MECP2-Mutation) older than 6 years will be included into this study. Children will be treated with oral FTY720 once daily. Safety will be assessed by clinical visits and by blood sampling. Efficacy will be measured by comparing BDNF-levels in blood and cerebrospinal fluid (CSF) before and under treatment and by measuring development of general as well as focal brain atrophy/volume by MRI (Magnetic Resonance Imaging) during the treatment period of one year. Clinical Scales will be used to study the children's skills before, under and after treatment. Results The study is ongoing with no safety concerns so far. Conclusions FINGORETT is a first phase I clinical study to assess safety and efficacy in children with Rett Syndrome. First results from this ongoing study show, that FTY720 is safe in children with Rett Syndrome above 6 years of age. FTY720 could be a possible treatment option for children with Rett Syndrome.

Early psychomotor development of children from triple pregnancy – case study

The aim of this study was to analyze the specificity and dynamics of psychomotor development in children from triplet pregnancy. &lt;br /&gt; The studied group was composed of siblings from triple pregnancy (T1, T2, T3), including two girls and one boy. This longitudinal study comprised three stages: stage I – children aged 25 months, stage II – children aged 29 months, and stage III – children aged 38 months. At each stage, the psychomotor development of children was examined with the Third Edition of Bayley Scales of Infant and Toddler Development (BSID-III) and subjectively by their mother. Additionally, medical and nursing documentation was analyzed.&lt;br /&gt; Individual psychomotor development of children from triple pregnancy is different with regards to various spheres, and has different rates and dynamics throughout consecutive years. &lt;br /&gt; Psychomotor development of children from triple pregnancies is determined by gender and postnatal clinical parameters, i.e. birth weight, head circumference, postnatal morbidity, and prematurity-related conditions.