Finnish children who experienced narcolepsy after receiving the Pandemrix vaccine during the 2009-2010 H1N1 pandemic demonstrated high level of psychosocial problems.

AIM: We assessed psychosocial burdens in children who developed narcolepsy after receiving the Pandemrix H1N1 vaccine during the 2009-2010 pandemic. Parental quality of life was also assessed. METHODS: This multicentre study covered four of the five Finnish University Hospital Districts, which dealt with about 90% of the paediatric narcolepsy cases after the Pandemrix vaccination. The medical records of children diagnosed from 2010 to 2014 were reviewed. The questionnaires included the Youth Self-Report (YSR), Children's Depression Inventory (CDI), the Child Behaviour Checklist (CBCL) and questions on parental resources, stress and quality of life. RESULTS: We obtained the medical records of 94 children who were aged 5-17 years at the time of their narcolepsy diagnosis and questionnaire data for 73 of those children. Most children had strong narcolepsy symptoms, and 25% had CDI scores that suggested depression. In addition, 41% had total CBCL problem scores above the clinically significant limit and 48% were anxious, withdrawn and had somatic complaints. Sleep latency was weakly associated with the CBCL total problem score. Half of the children needed psychiatric interventions and parental stress was common. CONCLUSION: Depression and behavioural problems were common in children with narcolepsy after the Pandemrix vaccination and their parents frequently reported feeling stressed.

Loss of DIAPH1 causes SCBMS, combined immunodeficiency, and mitochondrial dysfunction.

BACKGROUND: Homozygous loss of DIAPH1 results in seizures, cortical blindness, and microcephaly syndrome (SCBMS). We studied 5 Finnish and 2 Omani patients with loss of DIAPH1 presenting with SCBMS, mitochondrial dysfunction, and immunodeficiency. OBJECTIVE: We sought to further characterize phenotypes and disease mechanisms associated with loss of DIAPH1. METHODS: Exome sequencing, genotyping and haplotype analysis, B- and T-cell phenotyping, in vitro lymphocyte stimulation assays, analyses of mitochondrial function, immunofluorescence staining for cytoskeletal proteins and mitochondria, and CRISPR-Cas9 DIAPH1 knockout in heathy donor PBMCs were used. RESULTS: Genetic analyses found all Finnish patients homozygous for a rare DIAPH1 splice-variant (NM_005219:c.684+1G>A) enriched in the Finnish population, and Omani patients homozygous for a previously described pathogenic DIAPH1 frameshift-variant (NM_005219:c.2769delT;p.F923fs). In addition to microcephaly, epilepsy, and cortical blindness characteristic to SCBMS, the patients presented with infection susceptibility due to defective lymphocyte maturation and 3 patients developed B-cell lymphoma. Patients' immunophenotype was characterized by poor lymphocyte activation and proliferation, defective B-cell maturation, and lack of naive T cells. CRISPR-Cas9 knockout of DIAPH1 in PBMCs from healthy donors replicated the T-cell activation defect. Patient-derived peripheral blood T cells exhibited impaired adhesion and inefficient microtubule-organizing center repositioning to the immunologic synapse. The clinical symptoms and laboratory tests also suggested mitochondrial dysfunction. Experiments with immortalized, patient-derived fibroblasts indicated that DIAPH1 affects the amount of complex IV of the mitochondrial respiratory chain. CONCLUSIONS: Our data demonstrate that individuals with SCBMS can have combined immune deficiency and implicate defective cytoskeletal organization and mitochondrial dysfunction in SCBMS pathogenesis.

Bilateral Motor Responses to Transcranial Magnetic Stimulation in Preterm Children at 9 Years of Age.

OBJECTIVE: This study was aimed to evaluate motor tracts integrity in nondisabled preterm-born (PT) children at 9 years of age. METHODS: Overall, 18 PT and 13 term-born (T) children without motor disability were assessed by transcranial magnetic stimulation (TMS). Motor-evoked potentials (MEPs) were measured bilaterally from the abductor pollicis brevis (APB) and the tibialis anterior (TA) muscles. Muscle responses could be stimulated from all patients. RESULTS: Overall, 83.3 and 23.1% of PT and T children, respectively, had mild clumsiness (p = 0.001). One PT and three T children had immediate bilateral responses in the upper extremities. Seven PT children had delayed ipsilateral APB responses after left and ten after right TMS. Three controls had delayed ipsilateral responses. Ipsilateral lower extremity responses were seen in one PT after right and two PT children and one T child after left TMS. The results did not correlate to groups, genders, clumsiness, or handedness. CONCLUSION: Children of PT and T may have bilateral motor responses after TMS at 9 years of age. Ipsilateral conduction emerges immediately or more often slightly delayed and more frequently in upper than in lower extremities. SIGNIFICANCE: Bilateral motor conduction reflects developmental and neurophysiological variability in children at 9 years of age. MEPs can be used as a measure of corticospinal tract integrity in PT children.

Is Brain MRI Needed in Diagnostic Evaluation of Mild Intellectual Disability?

AIM: The purpose of our study was to suggest an imaging strategy and guidelines for the selection of the children with mild intellectual disability (ID) for magnetic resonance imaging (MRI), to avoid unnecessary imaging. METHODS: The brain MRIs and patient reports of 471 children were reviewed for the imaging findings and ID severity. The correlation between the clinical and brain MRI findings was analyzed in the 305 children with mild ID. RESULTS: Thirty-eight (12.5%) of the children with mild ID had significant abnormal brain MRI findings. Thirty-five of these had other neurological symptoms or diseases in addition to ID, which were an indication for brain MRI. In the logistic regression analysis, seizures (in patients without an epilepsy diagnosis), epilepsy, movement disorders, dysmorphia, encephalitis, traumatic brain injury, and abnormal head size were statistically significant symptoms or comorbidities associated with abnormal MRI findings. Only three children (1.0%) with mild ID had a significant MRI finding without any other clinical symptoms or disease. CONCLUSION: Routine MRI in children with mild ID without specific neurological symptoms, dysmorphic features, or related diseases is not suggested for revealing an etiology of mild ID. Since children with ID usually need to be sedated for MRI, routine imaging in the diagnostic evaluation of mild ID should be carefully considered. Clinical examination, other symptoms, and related diseases should be carefully assessed to decide the need for MRI.

Preoperative measurements on MRI in Chiari 1 patients fail to predict outcome after decompressive surgery.

BACKGROUND: The purpose of our study was to research the parameters of magnetic resonance imaging (MRI) that would predict the outcome of surgery in patients with Chiari 1 malformation (CM1) and to evaluate changes in MRI parameters after surgery. METHODS: Fifty-one patients (19 children, 13 adolescents, and 19 adults) operated on due to CM1 in Oulu University Hospital between 2004 and 2018 were evaluated. Seventeen parameters were measured from the preoperative MRI and 11 from the postoperative MRI. The correlations between the MRI parameters and the clinical variables before and after surgery were analyzed. RESULTS: The majority (88.2%) of the patients had favorable surgical outcomes. Postoperatively, subjective symptoms improved in 88.6% of the patients and syringomyelia in 81.8%. The location of the cerebellar tonsils, when measured in relation to the C2 synchondrosis or the end plate, postoperatively moved cranially in 51.0% (n = 26), did not change in 27.4% (n = 14), and moved caudally in 21.6% (n = 11) of the patients. However, neither the location of the tonsils nor any other parameters measured from pre- or postoperative MRI correlated with the patients' symptoms or surgical outcomes. CONCLUSIONS: No specific parameters on preoperative MRI evaluation were predictive of the outcome of surgery, emphasizing clinical examination in surgical decision-making. Furthermore, the postoperative MRI parameters did not correlate with the surgical outcomes. Thus, routine postoperative imaging is suggested only for patients with preoperatively diagnosed syringomyelia or worsening of symptoms.

Foetal growth restriction has negative influence on narrative skills in 8-10-year-old children.

AIM: The risk for neurocognitive difficulties is increased in children born with foetal growth restriction (FGR), but no data exist yet on their narrative skills. The narrative skills of 8- to 10-year-old children born with FGR between 24 and 40 weeks were compared with those of children born with appropriate growth for gestational age (AGA). METHODS: A prospectively collected cohort of 36 children with FGR was recruited prenatally at a Finnish tertiary hospital from 1998-2001, and 31 children with AGA served as controls. Narrative skills were assessed using a standardised test, and correlations between narrative, communication, reading and spelling skills were studied. RESULTS: Children born with FGR produced significantly less information and shorter utterances in their narratives than the AGA group. Children born preterm with FGR performed significantly more poorly in their narratives than the preterm AGA group. Poor narrative skills correlated with poor communication, reading and spelling skills. CONCLUSION: Children born with FGR had poorer narrative skills compared with their AGA peers at the age of 8-10 years, and narrative skills were linked to other language-based skills, which underlines the importance of early detection and preventive measures to optimise the educational outcome of children born with FGR.

Foetal growth restriction is associated with poor reading and spelling skills at eight years to 10 years of age.

AIM: Foetal growth restriction (FGR) is associated with communication problems, which might lead to poor literacy skills. The reading and spelling skills of eight- to 10-year-old FGR children born at 24-40 gestational weeks were compared with those of their gestational age-matched, appropriately grown (AGA) peers. METHODS: A prospectively collected cohort of 37 FGR and 31 AGA children was recruited prenatally at a Finnish tertiary care centre during 1998-2001. The children's reading and spelling skills were assessed using standardised tests for Finnish-speaking second and third graders. RESULTS: Significantly more children performed below the 10th percentile normal values for reading and spelling skills in the FGR group than in the AGA group. At nine years of age, the FGR children had significantly poorer performance in word reading skills and reading fluency, reading accuracy and reading comprehension than the AGA controls. No between-group differences were detected at eight years of age. CONCLUSION: FGR is associated with poor performance in reading and spelling skills. A third of the FGR children performed below the 10th percentile normal values at nine years of age. These results indicate a need to continuously evaluate linguistic and literacy skills as FGR children age to ensure optimal support.

Follow-up of pineal cysts in children: is it necessary?

PURPOSE: Pineal cysts are common incidental findings in children undergoing magnetic resonance imaging (MRI). Several studies have suggested MRI follow-up if the cyst is larger than 10 mm. However, cysts do not usually change during follow-up. Prevalence, growth, and structure of the pineal cysts were analyzed to decide if follow-up MRI is necessary. METHODS: A retrospective review between 2010 and 2015 was performed using 3851 MRI examinations of children aged 0-16 years to detect pineal cysts having a maximum diameter ≥ 10 mm. Eighty-one children with pineal cysts were identified and 79 of them had been controlled by MRI. Cysts were analyzed for the size, growth, and structure. RESULTS: A total of 1.8% of the children had a pineal cyst with a diameter ≥ 10 mm. Cysts were present in 48 girls (59.3%) and 33 boys (40.7%). Most pineal cysts (70/79) did not significantly grow during the follow-up (median 10 months, range 3-145 months). A total of 11.4% (9/79) of the cysts grew with the biggest change measured from the outer cyst wall sagittal anteroposterior dimension (mean 3.4 mm ± 1.7 mm). Only one cyst grew more than 5 mm. We found no factors correlating with the cyst growth among 9 cysts that grew > 2 mm. CONCLUSIONS: A majority of pineal cysts remained unchanged during the MRI follow-up. Results of this study suggest that routine MRI follow-up of pineal cysts is not necessary in the absence of unusual radiological characteristics or related clinical symptoms.

Very preterm children with fetal growth restriction demonstrated altered white matter maturation at nine years of age.

AIM: This study evaluated the role of preterm birth and fetal growth restriction on white matter maturation in schoolchildren without any severe neurodevelopmental impairment. METHODS: The study group comprised 56 very preterm children and 21 term children born between November 1998 and November 2002 at Oulu University Hospital, Finland. The mean gestational age of the preterm children was 28.7 (24.1-31.9) weeks. All children underwent diffusion tensor imaging at a mean age of 9.0 (8.6-9.6) years. Voxel-wise statistical analyses of the imaging data were carried out using tract-based spatial statistics. RESULTS: Preterm children with fetal growth restriction had lower fractional anisotropy and higher radial diffusivity than term controls (p < 0.05), bilaterally in several white matter areas. Preterm children without fetal growth restriction had higher mean diffusivity and axial diffusivity than term controls (p < 0.05) in analogous areas, but more asymmetrically. CONCLUSION: Preterm children had microstructural differences in white matter, compared to term-born children at a mean age of nine, and those with poor fetal growth showed widespread changes in white matter maturation compared to term-born children. Fetal growth and prematurity seemed to affect white matter maturation in a way that was still visible at that age.

Does Botulinum Toxin A Treatment Enhance the Walking Pattern in Idiopathic Toe-Walking?

Objective We conducted a randomized controlled trial to evaluate whether a combination of repeated botulinum toxin A (BTX-A) and conservative treatment is more effective in decreasing toe-walking than conservative treatment alone at 24 months follow-up. Patients and Methods Children between 2 and 9 years of age were randomized either into the conservative (CO) or botulinum treatment (BTX) group. The treatment in the CO group consisted of firm shoes, night splints, a home stretching program and physiotherapy. The BTX arm had all the same conservative treatments added with calf muscle BTX-A injections repeated in 6 months intervals if needed. Change in toe-walking pattern, ankle range of movement (ROM), and overall function were assessed at baseline and 6, 12, 18, and 24 months posttreatment. Results A total of 30 toe-walkers participated: 14 in CO and 16 in BTX group. At 24 months, all children in the BTX group and 85% in the CO group evaluated by the blinded physiotherapist (p = 0.065), 75% in the BTX group and 70% in the CO group graded by the research physiotherapist (p = 0.730), and 50% in the BTX group and 54% in the CO group reported by the parents ceased toe-walking (p = 0.837). The most prominent change was noted during the 1st year. The BTX group seemed to reach the goal earlier. No significant differences between the treatment groups in function or in ankle ROM ensued. Conclusion Adding BTX injections did not significantly enhance the goal to walk either flat foot or with heel strike at 24 months posttreatment.

Very preterm birth and foetal growth restriction are associated with specific cognitive deficits in children attending mainstream school.

AIM: This study investigated the association of prenatal and neonatal factors with cognitive outcomes in schoolchildren born very preterm without impairments at the age of nine. METHODS: We recruited a prospective regional cohort of 154 very low gestational age (VLGA) children of <32 weeks and 90 term-born comparison children born between November 1998 and November 2002 at Oulu University Hospital, Finland. Cognitive outcome was assessed using an inclusive neuropsychological test repertoire at the age of nine. RESULTS: The final study group comprised 77 VLGA children without cerebral palsy or any cognitive impairment and 27 term-born children. VLGA was associated with a 1.5-point [95% confidence interval (CI) 0.6-2.3] reduction in visuospatial-sensorimotor processing and a 1.2-point (95% CI 0.5-1.9) reduction in attention-executive functions scores. Foetal growth restriction (FGR) was the only clinical risk factor that was associated with cognitive outcome. Children with FGR had a significant decrease in language (1.7 points, 95% CI 0.50-3.0) and memory-learning (1.6 points, 95% CI 0.4-2.8) scores. CONCLUSION: Children born very preterm without impairments had poorer performance in specific neurocognitive skills than term-born children. FGR was an independent risk factor for compromised neurocognitive outcome in VLGA children and predicted difficulties in language, memory and learning.

Early vocalization of preterm infants with extremely low birth weight (ELBW), Part I: From birth to expansion stage.

The vocalization of preterm infants with extremely low birth weight (ELBW) up to the expansion stage was systematically described and compared with those of healthy full-term infants. The sample consisted of 18 preterm ELBW infants and the control group of 11 full-term infants. The follow-up was performed intensively using video-recordings. The vocalization of the preterm and full-term infants was analyzed quantitatively according to the categorical stages created by Oller. A descriptive analysis of all the vocalizations produced by the infants was performed. The preterm infants entered the primitive articulation stage later than the full-term infants and failed to produce more skills during that stage. According to this sample, there was no difference in entering the expansion stage, but the preterm infants failed to produce more skills than the full-term infants. The number of vocalization acts varied differently by age between the groups.

Early vocalization of preterm infants with extremely low birth weight (ELBW), Part II: From canonical babbling up to the appearance of the first word.

The aim of this study was to systematically describe the preverbal development of preterm infants from canonical babbling up to the first word and to compare it with that of healthy full-term infants. In addition, the amount of vocalization between the preterm and full-term groups was compared. The sample consisted of 18 preterm infants with extremely low birth weight and 11 full-term infants. The development of preverbal vocalization before variegated babbling did not differ between the groups. Instead, the preterm infants failed to produce more different kinds of canonical syllable types than the full-term infants. However, they showed a larger variance of variegated babbling skills and remained in the babbling phase longer before reaching the first meaningful word compared with the full-term infants. Following the onset of canonical babbling, the preterm infants produced fewer vocalizations than the full-term infants and they reached the first word later than the full-term infants.

Analysis of neurodevelopmental outcomes of preadolescents born with extremely low weight revealed impairments in multiple developmental domains despite absence of cognitive impairment.

BACKGROUND AND AIMS: Children with extremely low-birth weight (ELBW) have a high risk for cognitive, motor, and attention impairments and learning disabilities. Longitudinal follow-up studies to a later age are needed in order to increase understanding of the changes in neurodevelopmental trajectories in targeting timely intervention. The aims of this study were to investigate cognitive and motor outcomes, attention-deficit hyperactivity (ADHD) behaviour, school performance, and overall outcomes in a national cohort of ELBW children at preadolescence, and minor neuromotor impairments in a subpopulation of these children and to compare the results with those of full-term controls. The additional aim was to report the overall outcome in all ELBW infants born at 22 to 26 gestational weeks. METHODS: This longitudinal prospective national cohort study included all surviving ELBW (birth weight <1000 g) children born in Finland in 1996 to 1997. No children were excluded from the study. Perinatal, neonatal, and follow-up data up to the age of 5 years of these children were registered in the national birth register. According to birth register, the study population included all infants born at the age under 27 gestational weeks. At 11 years of age general cognitive ability was tested with the Wechsler Intelligence Scale for Children, ADHD behavior evaluated with a report from each child's own teacher (ADHD Rating Scale IV), and school performance with a parental questionnaire. An ELBW subpopulation consisting of a cohort representative children from the two university hospitals from two regions (n = 63) and the age-matched full-term born controls born in Helsinki university hospital (n = 30) underwent Movement Assessment Battery for Children and Touwen neurological examination comprising developmental coordination disorder (DCD) and minor neurological dysfunction (MND), respectively. RESULTS: Of 206 ELBW survivors 122 (73% of eligible) children and 30 (100%) full-term control children participated in assessments. ELBW children had lower full-scale intellectual quotient than controls (t-test, 90 vs 112, P < .001), elevated teacher- reported inattention scores (median = 4.0 vs 1.0, P = .021, r = .20) and needed more educational support (47% vs 17%, OR 4.5, 95% CI 1.6-12.4, P = .02). In the subpopulation, the incidences of DCD were 30% in ELBW and 7% in control children (P = .012, OR 6.0 CI 1.3-27.9), and complex MND 12.5% and 0%, (P = .052; RR 1.1 95% CI 1.04-1.25), respectively. Of survivors born in 24 to 26 gestational weeks, 29% had normal outcome. CONCLUSION: As the majority of the extremely preterm born children had some problems, long-term follow-up is warranted to identify those with special needs and to design individual multidisciplinary support programs.

Variations in prenatal sociodemographic factors associated with intellectual disability: a study of the 20-year interval between two birth cohorts in northern Finland.

The authors followed two cohorts of children born in northern Finland in 1966 (n = 12,058) and 1985-1986 (n = 9,432) to examine whether associations between maternal sociodemographic factors assessed during pregnancy and intellectual disability in the offspring changed over a 20-year interval. Both of the cohorts were followed up to the age of 11.5 years using similar methods and definitions of intellectual disability. Data on sociodemographic factors were based on comparable questionnaires returned by the mothers during the 25th week of gestation. Despite an interval of 20 years between the cohorts, the main indicators of socioeconomic disadvantage and maternal multiparity remained as having the largest impact on the incidence of intellectual disability, while single factors such as older maternal age at delivery, being single, and living in a remote area lost their association with intellectual disability. Over 20 years, prepregnancy maternal obesity (body mass index > or =30) became a newly associated factor (adjusted odds ratio = 2.8, 95% confidence interval: 1.5, 5.3). A future challenge is to explore the mediating mechanisms between intellectual disability and its associated preventable intergenerational environmental or lifestyle factors.

Etiology, syndrome diagnosis, and cognition in childhood-onset epilepsy: A population-based study.

OBJECTIVE: To evaluate the prevalence of various etiologies of epilepsies and epilepsy syndromes and to estimate cognitive function in cases of childhood-onset epilepsy. METHODS: A population-based retrospective registry study. We identified all medically treated children with epilepsy born in 1989-2007 in Finland's Kuopio University Hospital catchment area, combining data from the birth registry and the national registry of special-reimbursement medicines. We reevaluated the epilepsy diagnoses and syndromes and gathered data on etiologies and cognitive impairment. RESULTS: We identified 289 children with epilepsy. The annual incidence rate of epilepsies and epilepsy syndromes was 38 in 100,000, and the misdiagnosis rate was 3%. A specific etiology was identified in 65% of the cases, with a structural etiology accounting for 29% and a genetic or presumed genetic etiology for 32%. Most patients with unknown-etiology epilepsy had focal epilepsy and were of normal intelligence. Intellectual disability was detected in 35% of cases, and only 17% in this group had an unknown etiology for the epilepsy. Electroclinical syndromes (mainly West syndrome) were recognized in 35% of the patients. SIGNIFICANCE: Epilepsy is a complex disease that encompasses many etiologies and rare syndromes. The etiology and specific epilepsy syndrome are important determinants of the outcome and key factors in treatment selection. Etiological diagnosis can be achieved for the majority of children and syndromic diagnosis for only a third.

Etiological survey on intellectual disability in the northern Finland birth cohort 1986.

The etiology of intellectual disability was studied both in incident (n = 9,432) and prevalent (n = 9,351) populations in a one-year birth cohort born in Northern Finland in 1985-1986. Data from multiple sources were used to follow the children until the age of 11.5 years. Of the incident cases (n=119) with intellectual disabilities, 66.4% had etiologically biomedical associative factor. Paranatal factors were relatively fewer and prenatal more common compared with earlier studies. We found nearly double the prevalence of genetic factors leading to intellectual disabilities compared with a contemporary study from Norway. The differences between the populations, despite random variation, some dissimilarities between etiological categorization and diagnostic accuracy, are in most part due to true differences between the study populations and genetic pool.

Mitochondrial DNA Depletion and Deletions in Paediatric Patients with Neuromuscular Diseases: Novel Phenotypes.

OBJECTIVE: To study the clinical manifestations and occurrence of mtDNA depletion and deletions in paediatric patients with neuromuscular diseases and to identify novel clinical phenotypes associated with mtDNA depletion or deletions. METHODS: Muscle DNA samples from patients presenting with undefined encephalomyopathies or myopathies were analysed for mtDNA content by quantitative real-time PCR and for deletions by long-range PCR. Direct sequencing of mtDNA maintenance genes and whole-exome sequencing were used to study the genetic aetiologies of the diseases. Clinical and laboratory findings were collected. RESULTS: Muscle samples were obtained from 104 paediatric patients with neuromuscular diseases. mtDNA depletion was found in three patients with severe early-onset encephalomyopathy or myopathy. Two of these patients presented with novel types of mitochondrial DNA depletion syndromes associated with increased serum creatine kinase (CK) and multiorgan disease without mutations in any of the known mtDNA maintenance genes; one patient had pathologic endoplasmic reticulum (ER) membranes in muscle. The third patient with mtDNA depletion was diagnosed with merosine-deficient muscular dystrophy caused by a homozygous mutation in the LAMA2 gene. Two patients with an early-onset Kearns-Sayre/Pearson-like phenotype harboured a large-scale mtDNA deletion, minor multiple deletions and high mtDNA content. CONCLUSIONS: Novel encephalomyopathic mtDNA depletion syndrome with structural alterations in muscle ER was identified. mtDNA depletion may also refer to secondary mitochondrial changes related to muscular dystrophy. We suggest that a large-scale mtDNA deletion, minor multiple deletions and high mtDNA content associated with Kearns-Sayre/Pearson syndromes may be secondary changes caused by mutations in an unknown nuclear gene.

Evidence of a founder effect for the RETGC1 (GUCY2D) 2943DelG mutation in Leber congenital amaurosis pedigrees of Finnish origin.

Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies. It is a genetically heterogeneous condition as six disease-causing genes have been hitherto identified. Among them, RETGC1 (GUCY2D), is more frequently implicated in our series of LCA patients. Interestingly, 70 % of the families with RETGC1 mutations are originating from Mediterranean countries, the remaining families (30%) being originating from various countries across the world. Here, we report, the identification of the same homozygous RETGC1 nonsense mutation in three unrelated and non-consanguineous LCA families of Finnish origin, suggesting a founder effect. Interestingly, no linkage desequilibrium was found using polymorphic markers flanking the RETGC1 gene, supporting the view that the mutation is very ancient. Haplotype studies and Bayesian calculation point the founder mutation to 150 generations (95% credible interval 80-240 generations), i.e., 3000 years ago.

Brainstem auditory-evoked potentials of 8-year-old preterm children in relation to their psycholinguistic abilities and MRI findings.

BACKGROUND: Brainstem auditory potential (BAEP) has been used to demonstrate brainstem damage and to provide prognosis for the outcome for newborn children. There are contradictory results of its power to predict problems in language development or problems at school. It is well known that preterm children experience an excess of these problems. AIM: To study if BAEP findings of 8-year-old preterm children differ from those of the full-term born control children and whether there is correlation to their linguistic problems or to the findings in magnetic resonance imaging (MRI). STUDY DESIGN: Population-based cohort study. SUBJECTS: Forty-two preterm children aged 8 years born with birth weight <1750 g and their matched full-term control children with birth weight >2500 g, 24 of whom had BAEP recordings and MRI. OUTCOME MEASURES: Differences in BAEPs between the preterm and the control children. Correlation of BAEPs with linguistic problems and with MRI findings. RESULTS: No differences were found in the absolute latencies nor in the interpeak intervals and in the I/V amplitude ratio. Nor did the results differ even when cerebral palsy disabled preterm children, preterm children with mild neurodevelopmental dysfunction or healthy preterm children were compared to each other or to the control children. No correlation to the linguistic problems or to the findings of periventricular leukomalacia (PVL) in MRI or to the different measurements of the brainstem were found. CONCLUSION: If hearing impairment does not exist, BAEP does not give further information on neurodevelopmental nor linguistic problems of the preterm children.