Early Motor Milestones Research Articles

An 11-Year-Old Boy With Asperger’s Disorder Presenting With Aggression

“Alan” is an 11-year-old boy who was first seen in our clinic 3 years ago. His parents’ chief complaint at admission was Alan’s physically aggressive behavior at home, in particular toward his mother, as well as fights with children and teachers at school. Alan reportedly met his early developmental motor and cognitive milestones, but he showed difficulties with temper control and frustration tolerance as a toddler, having “significant fits” and biting other children. In preschool, Alan’s behavior was generally without significant aggression exceptwhen hismother was there to volunteer. In kindergarten, his parents reported, his behavior was managed with the help of a teacher who was very consistent with discipline and structure, but the followingyear,hisfirst-grade teacher providedmuch less structure, and Alan started getting into fights again with other children. His behavior also worsened at home; for instance, he would fight a neighbor boy and “the kids would scratch each other bloody.” The parents started family counseling at that time, which did not reduce the problem behaviors. In second grade, at the end of the first trimester, Alan reportedly “lost it.” After a family session, he “cleared the entire desk of the therapist” and “threatened to hurt the therapist.” At home, he would take knives from kitchen drawers and threaten family members. He would “shut down” and not talk about his feelings or thoughts. He was referred by the outpatient psychotherapist to the emergencydepartment and was subsequently treated in a day hospital program, which did reduce his outbursts. He was not put on medication. Discharge diagnoses were mood disorder not otherwise specified, rule out depressive disorder, and rule out anxiety disorder. After discharge, Alan was referred to our clinic. He continued to struggle with aggressive outbursts. When he was told to do minor chores or homework, he “would never do it.” Sometimes he would be “good” in themorning, but hismoodwasusually irritable, and little things would set off explosive outbursts, with yelling, throwing things, and punching people around him, resulting inbruises;his parentshad someconcern about the safety of Alan’s sibling, as well as their own safety. He had such outbursts approximately four times per week, each lasting 30 to 45 minutes. His parents also reported an apparent “female authority problem”; Alan responded much better to male authority figures than to women. During a review of Alan’s developmental history, his parents reported that their son had poor eye contact since early age and that he would “suppress” emotions and had a flat affect. They also noted that Alan did well approaching adults but did not attach emotionally to other children and struggled with making same-age friends. His own perception, however, was that he had many friends. Alan was always very much interested in science and was an expert in dinosaurs and rocks. “While other kids look at things in museums and move on,” he would read all the information he could get. Alan excelled in memorizing other people’s names and faces and after years would recognize someone he had seen only once. He was also noted to struggle with change in routines and to fidget with his hands. There was no history of abuse, contact with drugs or alcohol, mania, anxiety, ormajormedical illness. The family environmentwas reported as stable. Alan has one sibling, and no psychiatric family history was reported. Alan had never been hospitalized; he had been seen by three outpatient family therapists in the past, and, as noted, he had been in day hospital treatment. Alan himself reported that at times he did “not feel good,” but he denied depression or anxiety. He acknowledged having fights with other children but did not elaborate on circumstances. He reported hearing “animal voices” fromunder his bed or from the closet, but he could not really make them out. He felt there were ghosts and monsters in his room, and he was afraid of somebody pulling him down under his bed. When he looked, he reported seeing a lot of “stuff under his bed,” but denied seeing monsters. On further questioning, Alan said he thought those voices could be from the wind or his parents, but he was not certain about the absence of monsters. He had these experiencesmostly in thedarkness, atnight.Hedenied paranoia or ideas of reference.

P.15.12 Tubular aggregate myopathy caused by a heterozygous missense mutation in STIM1

This woman, now 33 years old, was first investigated at age 14 and previously described as a case report of tubular aggregate myopathy (Tulinius MH, Lundberg A, Oldfors A. Early-onset myopathy with tubular aggregates. Pediatric Neurol 1996;15:68–71). There was no family history of neuromuscular disease. Early motor milestones were normal. She never learned to run and at four years the parents noted she had a wide-based gait. At 12 years she lost the ability to rise from the squatting position without using her hands. The muscle weakness was slowly progressive over the years and she now presents with moderate proximal muscle weakness and wasting of both upper and lower extremities. She has slight ptosis and slight dysarthria but no ophthalmoplegia. CK has been constantly elevated 7–40 times upper normal levels. Muscle biopsy at age 14 and 30 years showed type 1 fiber predominance and numerous fibers (40–90% of all fibers), both type 1 and type 2, with tubular aggregates mainly located in the centre of the fibers and widely dispersed between myofibrils. Occasional necrotic fibers were present. Mutation analysis of STIM1 (stromal interaction molecule 1, the main Ca2 + sensor of the endoplasmic reticulum) revealed that the patient was heterozygous for a dominant missense mutation c.326A > G, p. p.His109Arg. This mutation was previously reported in two siblings in the original recent report describing mutations in STIM1 associated with tubular aggregate myopathy (Bohm J, Chevessier F, Maues De Paula A, et al. Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy. Am J Hum Genet 2013;92:271–8).

Infant motor milestones: poor predictive value for outcome of healthy children

Infant motor milestones: poor predictive value for outcome of healthy children

Parental reports on early language and motor milestones in fragile X syndrome with and without autism spectrum disorders

Objective: This study examined features of early language and motor milestones in children with fragile X syndrome (FXS) and contrasted these features with a diagnosis of Autism Spectrum Disorder (ASD) later in life in these children.Methods: We retrospectively examined parental report of age of onset for walking and first words for primarily boys with FXS, both with ASD (FXS + ASD) and FXS-only. The diagnosis of ASD was established by DSM-IV criteria, which were complemented by the ADOS. The age of onset was analyzed as a continuous and categorical variable, which were compared to the upper limit of typically developing children.Results: Individuals with FXS-only are more delayed in the onset of first words than first walks. The finding represents a pattern suggesting a continuum as robustly demonstrated in individuals with FXS + ASD vs. FXS-only.Conclusion: Our results support validity of FXS + ASD co-morbidity as a distinct phenotype in individuals with FXS.

Motor milestone development in young children with autism spectrum disorders: an exploratory study

This study aimed to determine if a sample of children currently diagnosed with autism spectrum disorders (ASDs) would have shown motor milestone delays before age three as compared to typically developing children. Given delays in motor skills, the study also strived to determine which specific skills might be delayed. Parents of 44 children who had been diagnosed with ASDs answered survey questions related to their child’s early motor milestone development. Survey responses were compared to Bayley’s motor milestone data for typically developing children. Results suggested that all 44 children (age range 82–90 months) with ASDs were delayed on all 26 motor milestones. Specifically, children with autistic disorder (n = 26) were significantly delayed on 11 motor milestones; nine of them delayed before age two. Children with Asperger Syndrome (n = 18) showed significant delay on four milestones; three of them delayed before the age of two.

Variations in early gross motor milestones and in the age of walking in Japanese children

Gross motor development is usually assessed in terms of age of achievement of motor milestones. Although there is generally an impression of faster development if the milestones are achieved at younger ages, no longitudinal studies have been done on the associations between the milestones, especially in Japan. As a part of the Japan Children's Study, the purpose of the present study was to determine whether the achievement of gross motor milestones in infancy is related with the age of walking. This was a prospective cohort study of 290 healthy and term infants born in a district of Osaka City, Japan. Three milestones (rolling over, sitting, and crawling) were observed in the laboratory for infants aged at 4 and 9 months by a pediatrician and a developmental psychologist, and the age of walking was confirmed in questionnaires filled in by the parents at 18 and 27 months. Children who could roll over at 4 months, and sit and crawl at 9 months, walked earlier than children who could not roll over, sit and crawl, respectively. With regard to crawling, children who were creeping had a 1 month delay in walking, and those who could not move forward had a 2 month delay compared to typical crawlers. On multiple regression analysis these three milestones were positively associated with walking: rolling over (β= 0.567), sitting (β= 1.973) and crawling (β= 1.473). The age and the patterns of sitting, crawling and rolling over were all related to the age of independent walking among Japanese infants. Consideration of milestone definition and variations is essential in medical check-up.

Prospective study of pandysmaturation and adult mental disorder in high-risk and normal-risk offspring

More than 50 years ago, Fish postulated that a special form of early abnormal neurodevelopment, “pandysmaturation”, defined a priori as constituting retarded cranial development in the first year of life, combined with delay in early motor milestone attainment, was related to genetic risk for schizophrenia, and was associated with schizophrenia-spectrum disorders in young adulthood. Fish confirmed this in a very small sample. We retested Fish’s postulation in a larger prospective study. Pandysmaturation was blindly investigated through medical records and prospective researcher and maternal observations, studying 75 “high-risk” offspring of women with a history of schizophrenia or affective psychosis and 91 “normal-risk” offspring. Subjects were studied prospectively from mother’s pregnancy to 22 years of age, at which time the offspring were independently assessed for schizophrenia-spectrum and affective disorders. Pandysmaturation ( n = 13, with 10 “definite” and 3 “probable” degrees) was significantly related to genetic risk for schizophrenia (Odds Ratio 4.9, p = 0.02) but not to genetic risk for affective disorders (OR 1.2, p = 0.81). Pandysmaturation was significantly associated with schizophrenia-spectrum (OR 6.2, p = 0.02), but not affective (OR 0.9, p = 0.90), disorders in young adulthood. Pandysmaturation was more strongly associated than was retarded cranial development, motor milestone delay, or social/cognitive milestone delay by itself. Pandysmaturation has efficacy as an early life risk-indicator of schizophrenia-spectrum disorder in young adulthood at least in subjects at genetic risk, strengthening the evidence for a generally genetic-based neurodevelopmental model of schizophrenia-spectrum (as contrasted with affective) disorders. Pandysmaturation is a risk-indicator for future schizophrenia-spectrum disorder, for potential use in scientific studies and clinical practice.

PSEUDODOMINANT INHERITANCE OF SPASTIC ATAXIA OF CHARLEVOIX-SAGUENAY

Spastic ataxia of Charlevoix-Saguenay (ARSACS, MIM 270550) is an early-onset neurodegenerative disease characterized by mild to moderate early-onset ataxia, spastic paraparesis, sensory motor neuropathy in the lower limbs, and almost invariably atrophy of the upper cerebellar vermis on brain MRI.1 Autosomal recessively inherited mutations in SACS have been described in several ethnicities and the range of mutations is growing rapidly.2 We report the clinical and molecular characterization of a family with an apparent vertical transmission of spastic ataxia where the pseudodominant transmission was explained by the combination of a large-scale deletion removing SACS with 2 novel nonsense variants. ### Case reports. The family pedigree is outlined in the figure. Patient II-1 is a 42-year-old woman. Early motor milestones were normal, but she was noted to be clumsy at school, with motor deterioration noted from age 16 years. At 24 years, neurologic examination showed cerebellar dysarthria, saccadic intrusions in pursuit eye movements, brisk arm and knee reflexes, absent ankle reflexes, and bilateral Babinski sign. Nerve conduction studies were not performed. A brain MRI scan disclosed thinning of the cervical cord but was otherwise unremarkable. When reassessed at age 34 years, her disability had progressed with an episode of diplopia and relapsing weakness. She had mild urinary urgency, and required a stick to walk. Her cognition was normal. Visual, auditory, and somatosensory evoked potentials showed delayed responses, and CSF examination showed oligoclonal bands. Brain MRI showed periventricular white matter abnormalities and mild cerebellar, brainstem, and cervical cord atrophy (figure, A–C). It was concluded that she had …

Brown-Vialetto-Van Laere Syndrome, a Ponto-Bulbar Palsy with Deafness, Is Caused by Mutations in C20orf54

Brown-Vialetto-Van Laere syndrome is a rare neurological disorder with a variable age at onset and clinical course. The key features are progressive ponto-bulbar palsy and bilateral sensorineural deafness. A complex neurological phenotype with a mixed picture of upper and lower motor neuron involvement reminiscent of amyotrophic lateral sclerosis evolves with disease progression. We identified a candidate gene, C20orf54, by studying a consanguineous family with multiple affected individuals and subsequently demonstrated that mutations in this gene were the cause of disease in other, unrelated families.

Parental infertility and developmental coordination disorder in children

It has previously been reported that children born after infertility treatment had a slight delay in early motor milestones. In this study, we examined whether children of infertile couples with or without infertility treatment had a higher risk of developmental coordination disorder (DCD). We used data on parental infertility and DCD among 23 167 singletons from the Danish National Birth Cohort (1996-2002). Data on time to pregnancy (TTP) and infertility treatment were collected early in pregnancy. Data on DCD in children were collected using the Developmental Coordination Disorder Questionnaire, filled in by the mothers during follow-up when the children were 7 years old. We used the recommended cut-off for the age group to classify children. Compared with children born of fertile couples, children conceived after a waiting TTP of longer than 12 months had a slightly higher risk of DCD [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.03-1.77], but the estimated OR was not significant in children born after infertility treatment (OR 1.19, 95% CI 0.86-1.66). None of the individual treatment procedures was significantly associated with a higher risk of DCD. Children of parents who had not planned their pregnancy showed no elevated risk. Our findings are overall reassuring, although it is possible that low fecundity may be associated with a modestly increased risk of DCD.

Are infants with torticollis at risk of a delay in early motor milestones compared with a control group of healthy infants?

Recently it has been claimed that infants with congenital muscular torticollis (CMT) are at risk of a delay in early motor milestones. The aim of the present study was to investigate whether infants with CMT are indeed at risk in comparison with a control group of healthy infants. A second aim was to investigate whether the time spent in a prone position and plagiocephaly had any influence on motor development. Eighty-two infants with CMT (35 females and 47 males) were compared with 40 healthy infants (18 females and 22 males). Motor development was assessed with the Alberta Infant Motor scale (AIMS). Multiple regression showed that infants in the CMT group had a significantly lower AIMS score than the control group at 2 months (p=0.03) and 6 months of age (p=0.05). Infants who spent at least three occasions daily in a prone position when awake had significantly higher AIMS scores than infants who spent less time prone at 2 months (p=0.001), 6 months (p<0.001), and 10 months of age (p<0.001). The CMT group achieved early motor milestones significantly later than the control group until the age of 10 months, but the risk of delay seems to be more strongly associated with little or no time prone when awake than with CMT.

Persistent CNS dysfunction in a boy with CMT1X

Objective X-linked Charcot Marie Tooth disease (CMT1X) is a hereditary demyelinating neuropathy caused by mutations in the GJB1 gene encoding the gap junction protein connexin 32 (Cx32). Some GJB1 mutations have been reported to cause transient clinical CNS dysfunction. We report a boy with persistent CNS abnormalities possibly caused by CMT1X. Methods A five year old boy was evaluated by clinical, electrophysiological, MRI and genetic testing. Results The patient's early motor milestones were normal to age 5 months. His subsequent course was one of slow improvement punctuated by brief periods of loss of ability to sit between age 5 and 10 months, loss of language between 12 months and 2 years and 1 episode of non-clinically observed resolved left-sided facial weakness. At age 5, he had truncal instability, appendicular ataxia, and dysarthric speech. Cognition was normal. He had mild toe weakness and intrinsic muscle atrophy. MRI evaluation was abnormal. Electrophysiologic testing revealed slowed motor conduction velocities and sensory responses of low amplitude. Genetic workup was normal excepting a novel missense mutation in GJB1, causing a p.54N > H substitution. Conclusion The patient has persistent CNS abnormalities characterized by dysarthria and ataxia. These are similar to transient CNS abnormalities reported in patients with CMT1X. These CNS findings may be the direct result of his novel Cx32 mutation.

Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis

BackgroundPrevious reports indicate an association between autism spectrum disorders (ASD) and disorders of mitochondrial oxidative phosphorylation. One study suggested that children with both diagnoses are clinically indistinguishable from children with idiopathic autism. There are, however, no detailed analyses of the clinical and laboratory findings in a large cohort of these children. Therefore, we undertook a comprehensive review of patients with ASD and a mitochondrial disorder.Methodology/Principal FindingsWe reviewed medical records of 25 patients with a primary diagnosis of ASD by DSM-IV-TR criteria, later determined to have enzyme- or mutation-defined mitochondrial electron transport chain (ETC) dysfunction. Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism. Twenty-one patients had histories of significant non-neurological medical problems. Nineteen patients exhibited constitutional symptoms, especially excessive fatigability. Fifteen patients had abnormal neurological findings. Unusual developmental phenotypes included marked delay in early gross motor milestones (32%) and unusual patterns of regression (40%). Levels of blood lactate, plasma alanine, and serum ALT and/or AST were increased at least once in 76%, 36%, and 52% of patients, respectively. The most common ETC disorders were deficiencies of complex I (64%) and complex III (20%). Two patients had rare mtDNA mutations of likely pathogenicity.Conclusions/SignificanceAlthough all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism.

Outcome of early intervention in infants at risk of developmental delay: a pilot study

Objectives To assess the outcome of a home based psychosocial intervention programme on facilitating development in infants at risk of developmental delay. Method Three groups of infants were involved. Group I comprised infants who suffered from adverse pregnancy and perinatal events and received psychosocial intervention. Group II comprised infants born during the same period with no similar risks and no intervention. Group III comprised infants who had adverse pregnancy and perinatal experiences but did not receive any intervention. Group 1 mothers were trained to carry out structured activities at home with the infant, adapted from the Portage Model. Outcome was measured at 12 months of age. The scores in 12 different skills in 5 developmental domains in the three sample groups were compared at the end of 12 months. Results Mean developmental scores in Groups (Gps) I (n=36), II (n=32) and III (n=9) were 10.00, 10.75 and 3.11 respectively. Independent sample t test showed no statistically significant difference in developmental scores at 12 months between Gps I and II (p=0.242, mean difference 0.750, 95% CI 2.019 to 0.519). Difference in developmental scores between Gps I & III was highly significant (p=0.000, mean difference 6.889, 95% CI 4.588 to 9.189). Conclusion Early intervention is effective and feasible in preventing developmental delay. ___________________________________________ 1 Professor of Psychological Medicine, Faculty of Medicine, Colombo. 2 Public Health Nursing Sister, MOH Division, Panadura (Received on 23 June 2006. Accepted on 20 July 2006). Introduction Prevalence of developmental disorders in children in non-industrialised countries is 12-29% 1 . Prevalence for Sri Lanka probably falls within this range, as indicated by population based studies. For example, a study, which assessed developmental readiness for school entry at 5 years of age, showed delayed cognitive development in 17.8%, leading them to being less ready to commence formal education 2 . Further, a study on mental health problems of urban preschool children identified delayed language development alone in 10% 3 . Many children with clinically identifiable developmental problems present late for medical help due to low rate of early recognition. For example, 34.5% of referrals to a specialist child mental health outpatient service were for developmental delay and learning disabilities, but the majority of referrals were over 5 years of age at the time of seeking help 4 . Though 49.9% of these children had delayed early motor and language milestones and 24.3% had suffered adverse birth and perinatal events, these negative prognostic indicators were not acted upon with earlier developmental interventions. In industrialized countries, community based intervention programmes for developmentally delayed children have been available for over three decades. These programmes are based on a range of biological, social-ecological and psychodynamic models. Irrespective of the cause of the developmental disorder, these intervention programmes are designed to improve skills, educational attainment and quality of life and prevent behavioural problems. A few such programmes are, the “Head Start” in the United States (US), “Sure Start” in the United Kingdom (UK) and “Portage Early Education Programme” in US and UK. Most programmes require high resource utilization and mainly target the infant and preschool age groups. Rationale for intervention commencing in infancy as opposed to preschool years is supported by recent advances in knowledge on neuro-biological processes associated with development. It has been shown that development of cognitive skills is related to significant structural changes in brain during perinatal period and first few months after birth. These changes include increase in brain weight and neuronal density, rapid dendritic arborisation and synaptogenesis and functional specialization 5,6 . Hence, the outcome of developmental intervention is optimal if applied in infancy as synaptic connections are unlikely to establish later. In addition, as the shaping of brain structures and strengthening of connections takes place, there is weakening and elimination of unused connections 7 . Therefore, psychosocial stimulation should be provided in infancy to obtain the best benefit. This approach is especially relevant for cognitive and language development, even though clinical evidence of developmental delay in these skills may not be apparent at this early stage. Considering the above mentioned evidence, this study examines the effectiveness and feasibility of using a psychosocial intervention programme in early infancy in those who are identified at birth with risk factors for later developmental delay.

22q11.2DS Deletion Syndrome: Developmental Milestones in Infants and Toddlers

The majority of children with 22q11.2DS deletion syndrome (22q11.2DS) have learning disabilities, and a substantial number have mental retardation. Although cognitive data have been reported on several samples of children with 22q11.2DS, data on their early developmental milestones are limited. The present study used a retrospective design and asked parents to recall developmental milestones. The participants were 88 children with 22q11.2DS, 47 community controls, and 29 sibling controls. Although very early gross motor and expressive language milestones did not differ significantly from comparison groups, subsequent gross motor and expressive language milestones did, suggesting that children with 22q11.2DS may begin to lag behind their peers sometime after the first year of life in these two domains. These patterns were also apparent when a subset of intellectually comparable children (22q11.2DS, n = 40 vs community controls, n = 24) was analyzed. We further found that receptive language and social adaptive milestones did not differ from comparison samples in either the early or later period. Receptive language delays were predictive of later Wechsler Intelligence Scale for Children-Third Edition Perceptual Organization Index scores, particularly in girls with 22q11.2DS. This suggests that although receptive language may be an area of relative strength in the developmental profile of young children with 22q11.2DS, even mild receptive delays should not be overlooked in early interventions with children with this disorder.

Síndrome de Down: evaluación del desarrollo psicomotor en menores de dos años y el impacto hacia la integración social y familiar

There are currently no specific tests to observe and assess development in infants with Down syndrome (DS), so follow-up programs and performance assessments are required. Moreover, such programs encourage early and appropriate intervention to ensure psychomotor and cognitive development to the child's full potential, paving the way for integration at school, at work, in society and within the family. This paper describes a longitudinal prospective study analysing and describing psychomotor and cognitive assessment in patients with DS in the first two years of life. The included subjects were infants with DS born in the Hospital Materno Infantil Ramón Sardá (HMIRS) as well as referrals from other institutions aged 1 day to 2 years. The subjects were evaluated over a 12-month period, with the Escala de Evaluación del Desarrollo Psicomotor (EEDP - Psychomotor Development Assessment Scale) by Rodríguez et al. and the Escala Argentina de Inteligencia Sensorio-Motriz (EAIS-Argentine Scale of Sensory-Motor Intelligence) by Oberman et al. administered monthly. This provided a mean age of acquisition of early motor milestones and a measurement of deviation from the population-wide mean in every area (language, motor skills, coordination, and social skills) with ensuing detection of the areas most compromised. A survey assessed the emotional, economic and social impact these children had on their families, and whether this impact might influence their development.

Down Syndrome: An Assessment of Infant Psychomotor Development and Its Impact on Social and Familial Integration

There are currently no specific tests to observe and assess development in infants with Down syndrome (DS), so follow-up programs and performance assessments are required. Moreover, such programs encourage early and appropriate intervention to ensure psychomotor and cognitive development to the child's full potential, paving the way for integration at school, at work, in society and within the family.This paper describes a longitudinal prospective study analysing and describing psychomotor and cognitive assessment in patients with DS in the first two years of life. The included subjects were infants with DS born in the Hospital Materno Infantil Ramón Sardá (HMIRS) as well as referrals from other institutions aged 1 day to 2 years. The subjects were evaluated over a 12-month period, with the Escala de Evaluación del Desarrollo Psicomotor (EEDP - Psychomotor Development Assessment Scale) by Rodríguez et al. and the Escala Argentina de Inteligencia Sensorio-Motriz (EAIS-Argentine Scale of Sensory-Motor Intelligence) by Oiberman et al. administered monthly.This provided a mean age of acquisition of early motor milestones and a measurement of deviation from the population-wide mean in every area (language, motor skills, coordination, and social skills) with ensuing detection of the areas most compromised.A survey assessed the emotional, economic and social impact these children had on their families, and whether this impact might influence their development.

A new type of leukoencephalopathy with metaphyseal chondrodysplasia maps to Xq25-q27

The authors report a three-generation family with four male patients presenting with a novel type of X-chromosomal leukoencephalopathy associated with skeletal abnormalities. The index patient and his brother reached their early motor milestones in due time and had normal language development. Between the ages of 2 and 3 years, first signs of spastic paraplegia were noticed. Furthermore, the patients developed tremor, ataxia, optic atrophy, and spastic tetraparesis. Both boys had broad wrists and knees without significant contractures. A maternal uncle and a granduncle had the same disease. Leukoencephalopathy (MRI, MRS) and metaphyseal chondrodysplasia (X-ray, MRI) were diagnosed. MRS showed a reduction of choline-containing compounds in the white matter. An autopsy on one of the patients, who died at age 37 years, revealed an orthochromatic type of leukoencephalopathy. In bone and cartilage tissue, unspecific signs of a mild chondrodysplasia were found. At the PLP gene locus an obligate recombination was observed, which excludes the Pelizaeus-Merzbacher locus on Xq21-22. However, affected males share a fragment of the long arm of chromosome X. The authors report a new type of leukoencephalopathy associated with metaphyseal chondrodysplasia located on Xq25-q27.

The Early Motor Milestones in Infancy and Later Motor Skills in Toddlers

The Early Motor Milestones in Infancy and Later Motor Skills in Toddlers

Influences on Achieving Motor Milestones: A Twin–Singleton Study

In order to determine if twinning impacted achievement of motor milestones the attainment of early motor milestones in twins was examined and compared to published data from singletons of the same age from the same culture and birth years. We examined the influence of twinning, sex, zygosity and birth cohort (1987-2001) on the motor development of twins aged 0 to 24 months. Data on the attainment of motor milestones (turn, sit, crawl, stand and walk) of twins were collected from maternal reports. All data were corrected for gestational age. Data from the twin sample were compared to normative data from singletons, which were available from Child Health Clinics (CHC). Analyses across twin data and the CHC singleton data revealed no differences between twins and singletons in achievement of motor milestones. Girls were able to sit without support slightly earlier than boys, otherwise there were no other sex differences. Birth-order analyses revealed minimal but significant differences in turning over from back to belly and for sitting without support between the first- and second-born. Dizygotic (DZ) twins were faster than monozygotic (MZ) twins in achieving the moment of sit, crawl, stand and walk. Twins born in earlier cohorts were faster in reaching the moment of crawl, sit and walk. It is concluded that there are no differences in time of reaching motor milestones between twins and singletons within the normal range. Sex has minimal to no effect on motor development in early childhood. DZ twins achieve motor milestones sooner than MZ twins. Attainment of gross motor milestones (crawl, stand and walk) is delayed in later birth cohorts.