Occipitofrontal Head Circumference Research Articles

Maternal drug or alcohol abuse is associated with decreased head size frommid-pregnancy to childhood.

Maternal alcohol abuse is poorly recognised and causes developmental problems. This study explored the foetal central nervous systems (CNS), head circumference and psychomotor development of children exposed to drugs or alcohol during pregnancy up to 2.5years of age. We recruited 23 pregnant women referred to Kuopio University Hospital, Finland, by their family doctor because of drug or alcohol abuse, and 22 control mothers. Foetal CNS parameters were measured by three-dimensional ultrasonography at the mean gestational age of 20weeks and the Griffiths Mental Developmental Scales (GMDS), and anthropometric measurements were carried out at the mean ages of one and 2.5years. The exposed foetuses had decreased biparietal and occipito-frontal distances and head circumferences, but unchanged cerebellar volume at 20weeks, and decreased head circumferences and length and height at birth, one and 2.5years of age. They scored lower than the controls on the GMDS general quotient and the hearing, language and locomotor subscales at 2.5years of age. Maternal alcohol or drug exposure was associated with decreased head size from mid-pregnancy to childhood and reduced development at 2.5years. Foetal head circumference at mid-pregnancy was a useful indicator of substance abuse affecting theCNS.

The alkylglycerol monooxygenase (AGMO) gene previously involved in autism also causes a novel syndromic form of primary microcephaly in a consanguineous Saudi family

Autosomal recessive primary microcephaly (MCPH) refers to a genetically heterogeneous group of neurodevelopmental disorders in which patients exhibit a marked decrease in occipitofrontal head circumference at birth and a variable degree of intellectual disability. To date, 18 genes have been reported for MCPH worldwide. We enrolled a consanguineous family from Saudi Arabia presenting with primary microcephaly, developmental delay, short stature and intellectual disability. Whole exome sequencing (WES) with 100× coverage was performed on two affected siblings after defining common regions of homozygosity through genome-wide single nucleotide polymorphism (SNP) microarray genotyping. WES data analysis, confirmed by subsequent Sanger sequence validation, identified a novel homozygous deletion mutation (c.967delA; p.Glu324Lysfs12*) in exon 10 of the alkylglycerol monooxygenase (AGMO) gene on chromosome 7p21.2. Population screening of 178 ethnically matched control chromosomes and consultation of the Exome Aggregation Consortium database, containing 60,706 individuals' exomes worldwide, confirmed that this mutation was not present outside the family. To the best of our knowledge, this is the first evidence of an AGMO mutation underlying primary microcephaly and intellectual disability in humans. Our findings further expand the genetic heterogeneity of MCPH in familial cases.

First Vault Expansion in Apert and Crouzon-Pfeiffer Syndromes: Front or Back?

Children with Apert and Crouzon-Pfeiffer syndromes are at risk of intracranial hypertension. Until 2005, when the authors switched to occipital expansion, their institution's preferred treatment was fronto-orbital advancement. However, it was still unclear whether (1) occipitofrontal head circumference (i.e., intracranial volume) was greater after occipital expansion than after fronto-orbital advancement; (2) the incidences of tonsillar herniation and papilledema were lower; and (3) visual acuity was better during follow-up. In these patients, the authors therefore compared fronto-orbital advancement with occipital expansion as the first surgical procedure. Measurements included repeated occipitofrontal head circumference as a measure for intracranial volume; neuroimaging to evaluate tonsillar herniation; funduscopy to identify papilledema; and visual acuity testing. The authors included 37 patients (Apert syndrome, n = 18; Crouzon-Pfeiffer syndrome, n = 19). Eighteen underwent fronto-orbital advancement and 19 underwent occipital expansion (age at surgery, 1.0 versus 1.5 years; p = 0.13). Follow-up time in both groups was 5.7 years. The increase in occipitofrontal head circumference (+1.09 SD) was greater after occipital expansion than after fronto-orbital advancement (+0.32 SD) (p = 0.03). After occipital expansion, fewer patients with Crouzon-Pfeiffer syndrome had tonsillar herniation (occipital, three of 11; fronto-orbital advancement, seven of eight; p = 0.02); for both syndromes together, fewer patients had papilledema (occipital, four of 19; fronto-orbital advancement, 11 of 18; p = 0.02). Visual acuity was similar after fronto-orbital advancement and occipital expansion (0.09 versus 0.13 logarithm of the minimum angle of resolution) (p = 0.28). The authors' preference for occipital expansion as the initial craniofacial procedure in Apert and Crouzon-Pfeiffer syndromes is supported by the greater increase it produces in intracranial volume (as evidenced by the occipitofrontal head circumference), which reduces the incidences of tonsillar herniation and papilledema. Therapeutic, III.

Brainstem auditory evoked responses in small-for-gestational age babies born at 30 and less weeks of gestation.

Brainstem auditory function is deviant from the normal in SGA babies born at 30 and less weeks of gestation. There is delayed brainstem neural maturation, which is associated with a small head size, and slightly precocial maturation in the more peripheral brainstem auditory regions. Intrauterine growth retardation has a subtle degree of adverse effect on central brainstem auditory pathway in preterm babies born at 31-36 weeks of gestation. Brainstem neural maturation is delayed, with slightly precocial maturation in the more peripheral brainstem auditory regions, in SGA babies born at 30 and less weeks of gestation.

Algorithm for the Management of Intracranial Hypertension in Children with Syndromic Craniosynostosis.

The purpose of this study was to examine the relationship of head growth, obstructive sleep apnea, and intracranial hypertension in patients with syndromic or complex craniosynostosis, and to evaluate the authors' standardized treatment protocol for the management of intracranial hypertension in these patients. The authors conducted a prospective observational cohort study of patients with syndromic craniosynostosis at a national referral center, treated according to a standardized protocol. Measurements included occipitofrontal head circumference, with growth arrest defined as downward deflection in occipitofrontal head circumference trajectory greater than or equal to a 0.5 SD fall from baseline over 2 years, or lack of change in occipitofrontal head circumference growth curve; sleep studies, with results dichotomized into no/mild versus moderate/severe obstructive sleep apnea; and funduscopy to indicate papilledema, supplemented by optical coherence tomography and/or intracranial pressure monitoring to identify intracranial hypertension. The authors included 62 patients, of whom 21 (33.9 percent) had intracranial hypertension, 39 (62.9 percent) had obstructive sleep apnea, and 20 (32.3 percent) had occipitofrontal head circumference growth arrest during the study. Age at which intracranial hypertension first occurred was 2.0 years (range, 0.4 to 6.0 years). Preoperatively, 13 patients (21.0 percent) had intracranial hypertension, which was associated only with moderate/severe obstructive sleep apnea (p = 0.012). In the first year after surgery, intracranial hypertension was particularly related to occipitofrontal head circumference growth arrest (p = 0.006). Beyond 1 year after surgery, intracranial hypertension was associated with a combination of occipitofrontal head circumference growth arrest (p < 0.001) and moderate/severe obstructive sleep apnea (p = 0.007). Children with syndromic craniosynostosis are at risk of intracranial hypertension. The major determinant of this after vault expansion is impaired head growth, which may occur at varying ages. The presence of moderate/severe obstructive sleep apnea also significantly increases the risk of intracranial hypertension. Risk, III.

Aicardi-Goutières syndrome mimicking congenital infection

 A 10-month-old infant was seen in our neurology department with concerns of developmental delay. She was unable to sit without support, had difficulty in fixing and following objects and parents had noticed an excessive startle response to low level noise (paper being ripped). She had a head lag, truncal hypotonia and brisk lower limb reflexes. She was born at term following an uneventful pregnancy. In the following months she made very slow developmental progress, her occipito-frontal head circumference declined from the 10 th centile to less than the 2 nd centile for age, she was noted to have horizontal nystagmus and chilblains like erythema in the extremities. Extensive investigations including metabolic studies and chromosome analysis were normal. Cytomegalovirus (CMV) was identified in the urine, although the serum serology was negative. Cerebrospinal fluid (CSF) for CMV polymerase chain reaction was negative. Serology for toxoplasmosis, rubella and herpes simplex infection was normal. She had normal calcium, phosphorus, parathormone, pyruvate and lactate levels. There was mild elevation of transaminases. Cranial magnetic resonance imaging showed generalized cerebral atrophy with white matter changes. Measurement of CSF biogenic amines and metabolites showed highly elevated biopterin (107 nmol/L; normal 8−57 nmol/L) and neopterin (506 nmol/L; normal 7−65 nmol/L). All other parameters were normal. Cranial computerized

Growth profiles of 34 patients with Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome (WHS) encompasses multiple congenital anomalies and mental retardation and is caused by partial deletions in the short arm of chromosome 4. Prenatal-onset growth deficiency is one of the WHS characteristics. Assessing and recording growth profiles of patients with WHS were the aims of this study. Anonymous questionnaire surveys were conducted with cooperation of a WHS peer-support group in Japan, and data from 34 WHS patients (12 males and 22 females; age, 1-23 years) were retrospectively collected. Height, weight, and head circumference (occipitofrontal head circumference) were measured and plotted on the standard growth charts of healthy Japanese children. Results indicated that most WHS patients showed growth retardation under the 3rd percentile since the first year of life and extremely poor body-weight gain after pubertal age. These findings are characteristic of WHS patients. The assessed growth patterns in this study could help monitoring and documentation of growth of WHS patients.

Effects of Serum 25-hydroxy-vitamin D and Fetal Bone Growth during Pregnancy.

BackgroundThis study was conducted to observe the prevalence of vitamin D deficiency during pregnancy and the effects of maternal 25-hydroxy-vitamin D (25-[OH]D) levels on fetal bone growth.MethodsFive hundred twenty-three Korean pregnant women were randomly recruited and serum 25-(OH)D level was measured. During pregnancy, fetal ultrasonography and serum 25-(OH)D measurements were carried out 3 times in 275 of 523 pregnant women. Fetal biparietal and occipitofrontal diameter, head and abdominal circumference, and femur and humerus length were measured through fetal ultrasonography.ResultsThe prevalence of vitamin D deficiency (25-[OH]D<20 ng/mL) based on the 1st serum measurement of 25-(OH)D was 88.9%. There was no association between maternal serum 25-(OH)D level and fetal bone growth. In 275 pregnant women who completed study design, the mean value of 25-(OH)D was 12.97±5.93, 19.12±9.82, and 19.60±9.98 ng/mL at 12 to 14, 20 to 22, and 32 to 34 weeks of pregnancy, respectively and there was an association between the difference of serum 25-(OH)D level between 12 to 14 and 20 to 22 weeks and growth velocity of fetal biparietal diameter between 20 to 22 and 32 to 34 weeks of pregnancy.ConclusionsThis study shows a high prevalence of vitamin D deficiency in Korean pregnant women and the change of serum 25-(OH)D levels is related with the growth of fetal biparietal diameter, however other parameters are not associated with serum 25-(OH)D levels.

Chromosomal rearrangements in patients with clinical features of Silver–Russell syndrome

Silver-Russell syndrome (SRS) is characterized by pre- and postnatal growth retardation, relative macrocephaly, asymmetry, and a triangular facial gestalt. In 5-10% of the patients the phenotype is caused by maternal UPD 7, and 38-64% of the patients present with hypomethylation at the imprinting center region 1 (ICR1) on 11p15.5. The etiology of the remaining cases is so far not known and various (sub-)microscopic chromosome aberrations with a phenotype resembling SRS have been published, especially duplication 11p15 (n = 15), deletion 12q14 (n = 19), ring chromosome 15, deletion 15qter, and various other mostly unique chromosomal aberrations (n = 30). In this study the phenotypes of these chromosomal aberrations were revisited and compared with the phenotypes of maternal UPD 7 and hypomethylation at ICR1 on 11p15.5. In some patients with a unique chromosomal aberration even the hallmarks of SRS were missing. Patients with duplication 11p15 show a more variable occipitofrontal head circumference at birth, a higher frequency of intellectual disability, and additional anomalies not reported in SRS. Deletion 12q14 is characterized by less severe pre- and postnatal growth retardation and less impressive relative macrocephaly. Patients with ring chromosome 15 and deletion 15qter have no relative macrocephaly (mostly even microcephaly) and more severe intellectual disability. Finally, deletion 15qter lacks the triangular facial gestalt. In summary, as SRS seems not an adequate diagnosis in many of these patients, diagnosis should focus on the chromosomal aberration than on SRS.

Impact of Periconceptional Multi-micronutrient Supplementation on Gestation: A Population-based Study

ObjectiveTo examine the effect of periconceptional multi-micronutrient supplementation on gestation and birth outcomes. MethodsA population-based community intervention program was conducted in 18 counties in China. Participants were divided into an intervention group, who received multi-micronutrient supplementation from at least 3 months before pregnancy throughout the first trimester, and a control group. Pregnant women were followed up to record information about birth outcomes. Maternal socio-economic characteristics and main birth outcomes were evaluated. Gestational age was further analyzed using survival analysis, to determine the time distribution of delivery. ResultsPericonceptional multi-micronutrient supplementation was associated with higher birth weight, birth length and occipitofrontal head circumference, and with lower incidence rates for stillbirth, low birth weight, and preterm birth. Moreover, periconceptional multi-micronutrient supplementation changed the time distribution of delivery, making the deliveries more clustered in the period between day 275 and day 295 of gestation. ConclusionOur study shows that periconceptional multi-micronutrient supplementation is beneficial for fetal development and optimizes all measured aspects of health in neonates in socioeconomically disadvantaged areas in China. The change in time distribution of deliveries caused by multi-micronutrient supplementation needs further clarification.

Early versus late administration of amino acids in preterm infants receiving parenteral nutrition.

Observational studies in preterm newborns suggest that delay in administering amino acids could result in a protein catabolic state and could impact on growth and development. To determine the effect of early administration of amino acids in premature newborns on growth, neurodevelopmental outcome, mortality and clinically important side effects. The standard search strategy of the Neonatal Review Group as outlined in The Cochrane Library was used. Relevant randomised controlled trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012 I ssue 9 ), MEDLINE, EMBASE and CINAHL from their earliest dates to September 2012. The trial registry portal of the World Health Organization's International Cilinical Trial Registry Platform and ClinicalTrials.gov (US National Institute of Health) was searched to identify ongoing and completed but unpublished studies. Randomised controlled trials comparing early administration of amino acids with late administration in premature newborn infants were included. Early administration of amino acid solution was defined as the administration of amino acids in isolation or with total parenteral nutrition within the first 24 hours of birth; late initiation was defined as the administration of amino acids in isolation or with total parenteral nutrition after the first 24 hours of birth. The primary outcome measures were growth, neurodevelopmental outcome and mortality at 28 days. The secondary outcomes were biochemical abnormalities, sepsis and mortality. Both review authors independently selected trials, assessed trial quality and extracted data from the included studies. We contacted authors for further information. Fixed-effect analyses were performed. The treatment effect was expressed as mean difference for continuous variables and as risk difference and risk ratio for dichotomous variables. All results included 95% confidence intervals (CIs). Seven randomised controlled trials were included in this review. One randomised controlled trial reported no difference in crown-heel length and occipitofrontal head circumference by day 10. Four trials that enrolled 93 premature infants showed positive nitrogen balance (The mean difference with 95% CI was 250.42 (224.91 to 275.93 P value < 0.00001). Four trials showed a significant difference in the level of blood urea nitrogen (BUN) in the first 48 hours (P value < 0.00001). Early administration of amino acids did not result in metabolic acidosis in the first 24 hours. There is no available evidence of the benefits of early administration of amino acids on mortality, early and late growth and neurodevelopment. There is evidence from four randomised controlled trials included in this review that early administration of amino acids is associated with a positive nitrogen balance. The clinical relevance of this finding is not known. Acid-base status and ammonia levels were normal in the infants who received amino acids early. Given the small number of infants in the randomised controlled trials included in this review, the clinical heterogeneity among them, and the lack of data on important clinical outcomes, there is insufficient evidence to guide practice regarding the early versus late administration of amino acids to infants less than 37 weeks gestation.

Longitudinal reference ranges for fetal ultrasound biometry in twin pregnancies

OBJECTIVE:The purpose of this study was to establish longitudinal reference ranges for fetal ultrasound biometry measurements and growth parameters in twin pregnancies.METHOD:A total of 200 uncomplicated twin pregnancies before 21 weeks of gestation were recruited for this prospective, longitudinal study. Women who abandoned follow-up, pregnancies with unknown outcomes or pregnancies with complications were excluded. Ultrasound scans were performed every three weeks, and biparietal and occipitofrontal diameters, head and abdominal circumferences, and femur diaphysis length measurements were obtained for each fetus at each visit. Estimated fetal weight, biparietal/occipitofrontal diameter, head circumference/abdominal circumference, and femur diaphysis length/abdominal circumference ratios were also calculated. Multilevel regression analysis was performed on normalized data.RESULTS:A total of 807 ultrasound examinations were performed in 125 twin pregnancies between 14 and 38 weeks of gestation (6.5±1.4 scans/pregnancy). Regression analysis demonstrated significant correlations for all variables with gestational age, namely log of the biparietal diameter (r = 0.98), log of the occipitofrontal diameter (r = 0.98), log of the head circumference (r = 0.99), log of the abdominal circumference (r = 0.98), square root of the femur length (r = 0.99), log of the estimated fetal weight (r = 0.99), biparietal/occipitofrontal ratio (r = -0.11), head/abdomen circumference ratio (r = -0.56), and log of the femur length/abdominal circumference ratio (r = 0.61). Values corresponding to the 10th, 50th, and 90th percentiles for estimated fetal weight at 28, 32, and 36 weeks, respectively, were as follows: 937, 1,096, 1,284 g; 1,462, 1,720, 2,025 g; and 2,020, 2,399, 2,849 g.CONCLUSION:In twin pregnancies, fetal ultrasound biometry measurements and growth parameters show a significant correlation with gestational age.

Reduced Brain Size of Very Preterm Infants at Term Equivalent Age Can be Estimated using Cerebral Ultrasound Measurements

Objective: To compare brain size between very preterm infants at term equivalent age (TEA) and term neonates using cerebral ultrasound (cUS) measurements and occipito-frontal head circumference (OFHC).Methods: We assessed prospectively a cohort of 88 preterm infants < 32 weeks gestation at TEA (mean postmenstrual age (PMA) 40.6 weeks) and 61 term controls (mean postnatal day 5.29, mean PMA 39.9 weeks). Infants with birth weight < 10th centile or major scan abnormality were excluded. A single observer made cUS measurements of biparietal diameter, brain structures, ventricles, extracerebral spaces and also OFHC. A mathematical model was built to estimate from the cUS measurements and OFHC the axial area of head, CSF-filled spaces and brain tissue. Statistical comparison was performed using independent samples t-test or Mann-Whitney test when appropriate and corrected for PMA at scan.Results: Preterms had a larger OFHC at TEA than controls (p=0.000), but total axial cranial area was similar (p=0.705). However, the CSF-filled spaces were significantly larger in preterm (p=0.000) than controls and estimated brain area in preterms was significantly smaller (p=0.000).Conclusions: Our data shows that estimated brain area in an axial plane is smaller in preterms, supporting the view that extra-uterine preterm brain growth is compromised, even in the absence of overt lesions. Preterm children without major lesions but smaller brains may be more at risk of neurodevelopmental problems (Horsch 2005) and our data suggests that cUS measurements may be useful in their identification. Long-term follow-up is being undertaken in this cohort.

Dietary Nucleotides and Early Growth in Formula-Fed Infants: A Randomized Controlled Trial

Dietary nucleotides are nonprotein nitrogenous compounds that are found in high concentrations in breast milk and are thought to be conditionally essential nutrients in infancy. A high nucleotide intake has been suggested to explain some of the benefits of breastfeeding compared with formula feeding and to promote infant growth. However, relatively few large-scale randomized trials have tested this hypothesis in healthy infants. We tested the hypothesis that nucleotide supplementation of formula benefits early infant growth. Occipitofrontal head circumference, weight, and length were assessed in infants who were randomly assigned to groups fed nucleotide-supplemented (31 mg/L; n=100) or control formula without nucleotide supplementation (n=100) from birth to the age of 20 weeks, and in infants who were breastfed (reference group; n=101). Infants fed with nucleotide-supplemented formula had greater occipitofrontal head circumference at ages 8, 16, and 20 weeks than infants fed control formula (mean difference in z scores at 8 weeks: 0.4 [95% confidence interval: 0.1-0.7]; P=.006) even after adjustment for potential confounding factors (P=.002). Weight at 8 weeks and the increase in both occipitofrontal head circumference and weight from birth to 8 weeks were also greater in infants fed nucleotide-supplemented formula than in those fed control formula. Our data support the hypothesis that nucleotide supplementation leads to increased weight gain and head growth in formula-fed infants. Therefore, nucleotides could be conditionally essential for optimal infant growth in some formula-fed populations. Additional research is needed to test the hypothesis that the benefits of nucleotide supplementation for early head growth, a critical period for brain growth, have advantages for long-term cognitive development.

United States Head Circumference Growth Reference Charts: Birth to 21 Years

To produce a more reliable, continuous set of occipitofrontal head circumference (OFC) growth reference charts for males and females from birth to adulthood in the United States. After investigating the strengths and shortcomings of previous reports, we combined the most recent statistically reliable reports of OFC growth reference data into a locally weighted regression analysis to estimate percentile curves. We used cross-sectional prospective local pediatric data to validate our results. We present new age- and sex-appropriate US OFC growth charts from birth to adulthood that include 3rd and 97th percentile cutoff values. Our local pediatric data validate that our new proposed OFC growth charts' assessment of attained OFC growth is comparable with previous references. We have eliminated disagreements between multiple current references by unifying previously reported US OFC data into a single set of smoothed male and female growth reference charts from birth to adulthood. This will reduce confusion or errors in interpretation of normal versus abnormal measurements currently encountered by primary care clinicians and subspecialists when using OFC growth charts for the US pediatric population.

Neuropathologic findings in patients with primary autosomal recessive microcephaly

Autosomal recessive primary microcephaly (MCPH, syn. Microcephalia vera) is a rare, genetically heterogeneous disease, in which patients exhibit microcephaly by the 32nd week of gestation. Genetic causes of MCPH subtypes 1–6 include mutations in genes encoding microcephalin (MCPH1), cyclin dependent kinase 5 regulatory associated protein 2 CDK5RAP2 (MCPH3), abnormal spindle-like, microcephaly associated ASPM (MCPH5), centromeric protein J CENPJ (MCPH6) as well as linkage to the two loci 19q13.1–13.2 (MCPH2) and 15q15-q21 (MCPH4). Severe microcephaly is characterized by a significantly reduced occipito-frontal head circumference (OCF) of more than three standard deviations below the mean for age, sex, and ethnicity. Microcephaly correlates closely with reduced brain volume and mental retardation, but patients with MCPH typically do not have further neurological findings. Imaging studies show brains of normal architecture but of reduced size. The latter is particularly evident in the cerebral cortex, which shows a simplified cerebral cortex structure, and there is also a slightly reduced white matter volume. Individual patients with MCPH provide evidence of periventricular neuronal heterotopias suggesting neuronal migration defects. It is not known whether the brain pathology in patients with MCPH is the result of defective cell proliferation/differentiation, cell migration and/or increased cell death. Neuropathological studies, which are rare and were performed at a time when a genetic diagnosis could not be performed, are thus highly warranted. Here, we summarize current knowledge on histological findings in MCPH patients. Infants with Microcephalia vera exhibited a significantly reduced brain volume with an almost preserved convolution pattern and no myelination disturbances. Cytoarchitectonic anomalies, seen predominantly in the first two cortical layers, included the appearance of compact cell clusters in the second layer. This can be interpreted as being indicative of a proliferation/differentiation and/or migration defect.

Occipital encephalocele and hypoplastic thumb: a nonrandom association of malformations

Summary The patient, a female, is the only child of a healthynonconsanguineous young couple. She has been followedup since 4 months of age because of congenitalnystagmus. She was born after an uneventful pregnancyby vaginal delivery at 36 weeks gestation with abirthweight of 2640g, length 46cm and head circumfer-ence 31cm. Motor and developmental milestones werewithin normal ranges. Language skills and academicperformance developed appropriate for her age. At 7years and 5 months of age, her height was 121cm (25–50centile), weight 23kg (25–50 centile) and occipitofrontalhead circumference 51.5cm (25–50 centile). No facialabnormalities were observed (Fig. 1a). A 3-cm diameterpainless nodular mass with soft tissue consistency wasobserved at the occipital vertex. The mass was reducibleon palpation, and size change also occurred during aValsalva manoeuvre. Asymmetric bilateral hypoplasticthenar eminences were noted as well as right thumbhypoplasia (Fig. 1c). A limited range of motion for activeadduction of the right thumb was also observed. She hadhorizontal nystagmus of low frequency; visual acuity was20/70 in both eyes after astigmatism correction withlenses. Ophthalmologic examination (slit-lamp biomicro-scopy, tonometry, visual field and dilated fundus exam-ination) did not reveal any further abnormalities. Nofamily history of radial defects was observed. Clinical andradiological examination of parents was normal.

Shwachman–Diamond syndrome is associated with structural brain alterations on MRI

Shwachman-Diamond syndrome (SDS) is an autosomal recessive condition that results from mutations in the SBDS gene, at chromosome 7q11. Main features include exocrine pancreatic failure, neutropenia and skeletal dysplasia. This study investigated brain structures by magnetic resonance imaging (MRI) in patients with SDS. MRI of the brain was performed in nine patients (7 males, age range 7-37 years) with SDS and mutations in the SBDS gene and in 18 age- and gender-matched controls. MRI images were assessed visually, and volumetric analyses of the brain matter and structural midsagittal measurements were performed. Eight out of nine SBDS mutation-verified patients reported learning difficulties. Patients with SDS had smaller occipitofrontal head circumferences than the controls (Z-score -1.3 vs. +0.3, P = 0.021), and decreased global brain volume (1.74 L vs. 1.94 L, P = 0.019); both gray matter (P = 0.042) and white matter (P = 0.007) volumes were reduced. Patients with SDS had no macroscopic brain malformations, but they had significantly smaller age- and head size-adjusted areas of posterior fossa (P = 0.006), vermis (P = 0.002), corpus callosum (P = 0.020), and pons (P = 0.002), and significantly larger cerebrum-vermis ratio (P < 0.0001) than the healthy controls. SDS patients had structurally smaller posterior fossa and cerebellar vermis, corpus callosum, and brainstem than the healthy controls. The MRI findings may be related to the neuropsychological features described in SDS.

Effect of high versus low initial doses of L-thyroxine for congenital hypothyroidism on thyroid function and somatic growth

Background and aims:The optimal dose of thyroxine (T4) in congenital hypothyroidism (CH) during infancy is controversial. Higher doses lead to improvement in cognitive scores, but have been linked to later...

The growth of twins between the ages of 2 and 9 years

Background: Twin growth studies are mostly based on pooled data without consideration of zygosity, parental heights or birth weight.Aim: The study investigated the effects of gender, zygosity, parental height and birth weight on subsequent twin growth.Methods: Height and weight measurements of 1533 twins (n = 1077 for occipito-frontal head circumference (OFC)), age range 2–9 years, were converted to standard deviation scores derived from singleton standards. Their growth was evaluated in relation to gender, zygosity, parental heights and birth weight.Results: Mean stature of twins fell only slightly below the reference values of singletons, but they were underweight to a greater extent (boys more than girls). Twins’ OFC were low (girls more so than boys). Monozygotic (MZ) twin boys were lighter and shorter than dizygotic twins and MZ twin girls. Deficient growth was most evident in those babies light at birth. Parental heights only partly accounted for the difference in height of twins.Conclusions: Birth weight and parental height are important in relation to subsequent growth. Boy twins are at a disadvantage compared with girls in terms of their growth in height and weight, particularly in the low birth weight and MZ groups.