Abstract Background Late-preterm infants represent 70% of the whole preterm population. Aims To establish the range and frequency distribution of neonatal neurological scores in a large cohort of low ...risk late-preterm infants and the possible differences with full-term infants. Methods Three hundred-seventy-five healthy infants born between 34 and 36 weeks gestational age (GA) without major brain lesions were assessed between 39 and 41 weeks post-menstrual age using the Hammersmith Neonatal Neurologic Assessment and compared to the scores obtained using the same examination in full-term infants. Results Infants born at 35 and 36 weeks GA had similar median scores in 32 of the 34 items. Infants born at 34 weeks GA had a different profile of scores compared to those born at 35 and 36 weeks, mainly in the tone items. While in infants born at 34 weeks the assessment at term age showed similar median scores to those obtained in full-term infants in 25/34 items, in those born at 35 and 36 GA the number of scores similar to full-term infants increased to 29/34. The main differences involved the tone items, with more marked flexor tone in the limbs and better head control for those born at 35 and 36 weeks. Conclusions This data can help as reference data when examining late-preterm infants at term age to see where the individual child stands compared to age matched low risk infants and to identify signs that are outside the reported range in infants with lesions or other risk factors.
The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of ...overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM.
Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassing ZIC1 and ZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions of ZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q.
Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity of ZIC1-ZIC4 genes is neither necessary nor sufficient per se to cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS.
Abstract The following is a report on a large family with 5 males affected by the X-linked recessive form of Emery–Dreifuss muscular dystrophy with mutation in the STA gene. A detailed longitudinal ...cardiological evaluation and muscle imaging studies allowed for the assessment of intrafamilial variability of cardiac and muscle involvement. Long term cardiological follow up in the 5 affected males and in 7 female carriers revealed different degrees of severity, ranging from tachycardia–bradycardia syndrome and variable biatrial and left ventricle dilatation, to an episode of isolated symptomatic sustained ventricular tachycardia requiring a device implantation. Muscle imaging in the affected males showed involvement of the soleus and medial head of gastrocnemius on leg muscles and variable involvement on thigh muscles that have not been previously reported. In some cases, imaging showed clear signs of muscle involvement even when no overt signs of weakness could be detected during clinical examination.
We report muscle MRI findings of 10 patients from 8 families with nemaline myopathy. Patients with involvement of the nebulin (NEB) gene showed a consistent pattern of selective muscle involvement ...corresponding to clinical severity. In mild cases, there was complete sparing of thigh muscles and selective involvement of tibialis anterior and soleus. In moderate cases, there was predominant involvement of rectus femoris, vastus lateralis and hamstring muscles and diffuse involvement of anterior compartment and soleus. Patients with nemaline myopathy secondary to mutations in the skeletal muscle alpha-actin (ACTA1) gene showed diffuse involvement of thigh and leg muscles with relative sparing of the gastrocnemii. Selective muscle involvement in both genetic categories was distinct from what has been reported in other congenital myopathies. We conclude that muscle MRI may be applied to distinguish nemaline myopathy from other conditions with similar clinical and histopathological features, to supplement clinical assessment in individual patients and to help direct genetic testing.
Ullrich congenital muscular dystrophy (UCMD) is a form of merosin-positive congenital muscular dystrophy characterized by proximal contractures, distal laxity, rigidity of the spine, and respiratory ...complications. Recently, a deficiency of collagen VI on muscle and skin biopsy together with recessive mutations in the collagen 6A2 gene were reported in three families with UCMD. However, the clinical spectrum, frequency, and level of heterogeneity of this disorder are not known.
The authors studied 15 patients (aged 3 to 23.6 years) with a clinical diagnosis of UCMD. Linkage analysis to the three collagen VI genes was performed in all informative families (n = 7), whereas immunohistochemical analysis of collagen VI expression in muscle was performed in the remaining cases.
An immunocytochemical reduction of collagen VI was observed in six patients. Three of the six patients belonged to informative families, and haplotype analysis clearly suggested linkage to the COL6A1/2 locus in two cases and to the COL6A3 loci in the third case. In the remaining nine patients, primary collagen VI involvement was excluded based on either the linkage analysis (four families) or considered unlikely based on normal immunolabeling of collagen VI. Age and presentation at onset, the distribution and severity of weakness and contractures, and the frequency of nonambulant patients were similar in the patients with and without collagen VI involvement. Distal laxity, rigidity of the spine, scoliosis, failure to thrive, and early and severe respiratory impairment were found in all patients by the end of the first decade of life, irrespective of their maximum motor functional ability or their collagen status.
These results suggest that collagen VI involvement is relatively common in UCMD (40%); however, the role of this molecule was excluded in a number of cases, suggesting genetic heterogeneity of this condition.
The aim of this retrospective study was to establish the presence and severity of cerebral visual impairment in preterm infants with PVL. We also wished to establish whether abnormalities of visual ...function are related to brain MRI findings and more specifically not only to the involvement of optic radiations and occipital cortex but also to changes in the thalami, that are often affected in infants with PVL.
Twelve infants with cystic PVL were assessed at 1 year (+
2) corrected age with a battery of tests specifically designed to assess various aspects of visual function in infancy, such as ocular movements, visual acuity, visual fields and fixation shift. All infants also had a brain MRI.
Eleven of the 12 had involvement of the optic radiations: all had some abnormalities of visual function and visual impairment was more severe in infants with more extensive involvement of the optic radiations. The child with normal optic radiations had normal visual function.
Six of the 12 infants also had obvious signs of atrophy of the thalami and all had severe and wide-ranging abnormalities of visual function in all testing domains. Two children had equivocal atrophy of the thalami, both had some abnormalities of visual function.
Four children had normal thalami and had normal visual function or only minor abnormalities on one of the visual tests. Our results suggest that the atrophy of the thalami may play an additional role in the abnormal development of visual function in infants with PVL and abnormal optic radiations.
The aims of the present study were: to examine the quality of life (QOL) of parents of children with cerebral palsy (CP) and to establish the possible effect of behaviour problems on their QOL. ...One-hundred children with CP, aged between 4 and 10 years, and both their parents were included in the study. Both parents completed the WHOQOL-BREF, to assess their QOL. A sample of 60 parents of healthy children was used as control group. The primary caregiver also completed the CHILD BEHAVIOUR CHECKLIST (CBCL). Parents of children with CP showed lower scores on physical and psychological domains than the control group on QOL. In the psychological domain the mothers of children with hemiplegia had the lowest scores. The mothers reported lower scores than the fathers for the physical domain in the group of children with diplegia and quadriplegia and for the psychological domain in the group of children with hemiplegia. Children with hemiplegia showed externalizing scores at CBCL higher than the other groups, that could explain the poorer QOL scores of their mothers. In conclusions our results provide useful information on the QOL in families with different forms of CP, useful in planning interventions for the family of children with CP.
to investigate visual function pre- and post surgery in children with single-suture non-syndromic craniosynostosis
Twenty-nine infants (12 with sagittal synostosis, 10 with trigonocephaly and 7 with ...anterior plagiocephaly) were longitudinally evaluated using a battery of tests assessing various aspects of visual function, including ocular behaviour, acuity, visual fields and fixation shift. All infants were assessed before surgery and 2, 6 and 12 months after surgery.
Before surgery only 16% of infants had completely normal visual function, while on the assessment performed 12 months after surgery, the number with normal results on all the tests increased to 65%. The only abnormalities found 12 months after surgical correction were mainly found on abnormal oculomotor behaviour in infants with plagiocephaly.
Abnormalities of visual function were not frequent in infants with non-syndromic craniosynostosis who underwent surgical correction. Approximately half of the patients had some visual abnormalities before surgery, which subsequently improved, showing a delayed visual maturation rather than persistent abnormalities.
Fibroblast growth factors (FGFs) are important signaling molecules which act during early vertebrate central nervous system development.
FGF17
, together with FGF8, is a key factor in the patterning ...of the mid-hindbrain region with a complex picture of spatiotemporal gene expression during the various stages of cerebellar development. Disruption or reduced expression of
fgf17
in mice has been associated with cerebellar vermis abnormalities. We have identified a
de novo
2.3-Mb deletion of chromosome 8p21.2-p21.3 in a girl with severe growth retardation, seizures, and classical Dandy–Walker malformation. Analysis of gene expression in blood lymphocytes and skin fibroblasts revealed markedly reduced levels of
FGF17
, which is located 1 Mb from the proximal deletion breakpoint. This is the first report of a human cerebellar malformation associated with transcriptional downregulation of the
FGF17
gene.
PDF
