Structural brain anomalies in Cri-du-Chat syndrome: MRI findings in 14 patients and possible genotype-phenotype correlations.

INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings. PATIENTS AND METHODS: Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution. RESULTS: MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients. CONCLUSIONS: Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.

Usefulness of an early neurofunctional assessment in predicting neurodevelopmental outcome in very low birthweight infants.

OBJECTIVE: To evaluate whether early neurofunctional assessment may be useful in predicting neurodevelopmental outcome in children of very low birth weight (VLBW). DESIGN: Observational longitudinal study. SETTINGS: Northern Italy. PATIENTS: A total of 250 VLBW children (129 boys, 121 girls) born consecutively 1996-1999. MAIN OUTCOME MEASURES: Neurodevelopment at 36 months of chronological age, classified in accordance with the classification of Tardieu and the International classification of functioning. RESULTS: Of the infants exhibiting normal neurodevelopment (n = 183) or major dysfunction (n = 17) at 3 months of corrected age, 72% and 94% respectively did not change their score during the study. Minor dysfunctions at 3 months of corrected age were transient in 17 (34%) children. After adjustment for neonatal variables, neurodevelopment at 3 months of corrected age remained predictive of dysfunction at 36 months (odds ratio = 4.33, 95% confidence interval 2.05 to 9.12). If the results for the normal and minor dysfunction groups were pooled, the predictive qualities of the 3 month neurofunctional assessment were: sensitivity 0.5, specificity 0.99, positive predictive value 0.94, negative predictive value 0.93. CONCLUSION: Early neurofunctional evaluation may be useful in predicting later neurodevelopmental outcome in VLBW children.

The effects of an early developmental mother-child intervention program on neurodevelopment outcome in very low birth weight infants: a pilot study.

BACKGROUND: Several studies report increased minor neurodevelopment dysfunctions in children born very low birth weight (VLBW). Usefulness of preventive early intervention programs to improve neurodevelopment outcome of VLBW infants is still under investigation. AIMS: To evaluate the effects of an early post-discharge developmental mother-child intervention program on neurodevelopment outcome at 36 months in VLBW infants. STUDY DESIGN: Prospective study. SUBJECTS: 36 VLBW infants ([mean (S.D.)] birthweight=864 g (204 g); gestational age=27.9 weeks (2.4 weeks)), consecutively born January-August 2001, randomized in intervention and control groups. OUTCOME MEASURES: Neurodevelopment assessment at 36 months of chronological age with use of the Griffiths Mental Development Scale and related subscales. RESULTS: At 36 months of chronological age, as compared to controls, children in intervention group exhibited higher scores in personal-social subscales ([mean (S.D.)]=101.4 (9.3) vs. 92.9 (12.1), P=0.02), eye-hand coordination (92.7 (4.5) vs. 87.1 (9.9), P=0.041), practical reasoning (98.6 (8.2) vs. 89.4 (10.1), P=0.01). Development Scale were 97.6 (5.5) and 92.4 (9.9), respectively, in intervention and control groups (P=0.074). CONCLUSIONS: Early post-discharge developmental mother-child intervention program may have a positive effect on later neurodevelopment outcome of VLBW children.

[Disability in childhood. Care and professional training regarding particularly the problems currently seen in long-term control of newborns at risk]. / La disabilita' in eta' pediatrica. Assistenza e formazione professionale con particolare riguardo ai problemi attualmente osservati nel controllo a distanza del neonato a rischio.

Children with disability are a heterogeneous population distributed between complex conditions including physical disorders, psychomotor and neurodevelopment disorders, social role and school activities limitations. Prenatal, perinatal and neonatal diseases together with disabling chronic conditions may cause childhood disability. Data from literature show a prevalence of childhood disability ranging from 5 to 20% with a wide range of severity level. The social impact of childhood disability is extremely relevant. Children with disabilities frequently require health care services and special education. VLBW (very low birth weight infants, birth weight <1500 gr) have major disabilities (10-15%) while minor disabilities can be found in 20-25% of these subjects. The first step stays in medical prevention but also an oriented training toward these problems for doctors both in pre and post-graduate formation can play a significant role. Support of society in order to understand the complexity and heterogeneity of childhood disability, through social care services, is mandatory. These measures, apparently costly, if correctly done, will be helpful for both the individual subject and the whole society, through a reduction of the disability problems and the final economy cost impact.

Usefulness of ICF-CY to define functioning and disability in very low birth weight children: a retrospective study.

BACKGROUND: Preterm birth is associated with variable degrees of brain injury, adverse neurodevelopmental outcomes and continuing special health care needs. STUDY AND AIMS: This observational, retrospective and cross-sectional study aims to describe the functional features of VLBW infants using the ICF-CY classification and to identify the association between gender, twinship, birth weight, gestational age, adjusted age and functioning as defined by the ICF biopsychosocial model. SAMPLE: 56 VLBW infants (corrected age of 12-24 months) were consecutively enrolled. INSTRUMENTS: Three assessment tools were used: a neuro-functional assessment (NFA); the Griffiths Mental Development Scales-Revised: Birth to 2 years (Griffiths 0-2) to evaluate psychomotor development and the ICF-CY questionnaire for ages 0-3. RESULTS: A two-step cluster component analysis with the Bayesian information criterion was conducted based on NFA and Griffiths 0-2 scores and four groups of infant's functioning (very low, low, intermediate, high) emerged. Study findings demonstrate that the traditional assessment tools tend to poorly evaluate the interaction between the person's functioning and environment factors (EF), even thought EF results to be relevant for VLBW infants. The higher number of symptoms, more difficulties in activities and participations and the higher number of environmental facilitators maximize the difference between infants with very low and those with intermediate or higher functioning. The distribution of gender or the presence of siblings is not significantly associated to any group. CONCLUSION: This study shows that a more complete evaluation of functioning of VLBW children, based on the biopsychosocial approach, is needed and can be successfully implemented in the follow-up routine through ICF-CY questionnaire.

"Postural Management" to prevent hip dislocation in children with cerebral palsy.

Muscolo-skeletal disorders and hip deformity play a key role on future development of motor and adaptive functions in children with cerebral palsy (CP). Lateral migration of the femoral head increases on average 7.7% per year and may progress in association with acetabular dysplasia to hip dislocation. Conservative preservation of muscle length and balance may prevent or reduce femoral head migration and acetabular dysplasia. Equipment for position lying, sitting, and standing is an established method of maintaining muscle length and joint range. French approach (Le Métayer et al) include the use of customised plaster cast orthoses, for sitting and standing positions, called siège moulé and gouttière, tailor-made according to the child's muscolo-skeletal characteristics and motor abilities. At our department, hips with clinical and radiological evidence of displacement unresponsive to pharmacological and surgical treatment were treated with postural management. The two cases we show in this paper underwent a physiotherapy programme (neurodevelopment treatment) twice a week and a seated postural programme 5 hours a day with the siège moulé. Hip radiographs were measured with the migration percentage (MP) described by Reimers. The follow-up measurements showed a progressive reduction of MP values of the hip treated, confirming the significant benefit from the combined non surgical approach. The study supports the evidence that conservative management of hip deformity with siège moulé can be successful if implemented before the development of hip dysplasia.