Normal Head Circumference Research Articles

Determine the Frequency of Sensorineural Deafness in Children with Cerebral Palsy

Aim: To determine the frequency of sensorineural deafness in child with cerebral palsy. Study Design: Descriptive/cross-sectional Place and Duration of Study: Department of Neurology, Chandka Medical College Hospital, Larkana from 1st October 2020 to 31st March 2021. Methodology: One hundred and seventy patients of both genders age between 1-14 years were enrolled. Children diagnosed as having cerebral palsy and fulfilling the inclusion criteria was included. Hearing assessment was done with audiometry and degree of hearing loss was recorded in both ears in the form of mild, moderate, severe and profound degree of hearing loss. Results: Most of the patients 90 (52.94%) were between 1-5 years old followed by 51(30%) patients between 5-10 years with mean age of 4.8±7.8 years. 115 (67.65%) cases were males and 55 (32.35%) females. 54 (31.8%) cases had microcephaly and116 (68.2) cases had normal head circumference. Among 170 cases of cerebral palsy 48 (28.23%) cases had hearing loss and 122 (71.77%) of patients of CP had no hearing deficit. Among 48 cases of CP with hearing loss 15 (31.25%) cases had mild, 14 (29.17) cases had moderate, 10 (20.83%) had severe and 11 (22.92%) cases had profound hearing loss. Conclusion: The frequency of sensorineural deficit is high and significantly associated with cerebral palsy patients. Keywords: Degree of hearing loss, Sensorineural hearing loss, Cerebral palsy

Physical Growth and Neurodevelopment of a Cohort of Children after 3.5 Years of Follow-up from Mothers with Zika Infection during Pregnancy-Third Report of the ZIKERNCOL Study.

In utero Zika virus (ZIKV) exposure has been related to a group of congenital structural abnormalities called the congenital Zika syndrome, which also has been related to neurodevelopment alterations even in normocephalic children. Physical growth has been less explored, and delayed growth and malnutrition have been reported. The objective of this study is to describe the growth and neurodevelopment features of normocephalic infants born from a cohort of mothers with RT-PCR confirmed ZIKV during pregnancy in Risaralda, Colombia. We conducted a retrospective cohort, including normocephalic children born from mothers with RT-PCR confirmed ZIKV infection during pregnancy in Risaralda, Colombia. Physical growth was measured using WHO standards, and neurodevelopment was measured with the abbreviated neurodevelopment scale 2 validated for Colombia. After verifying inclusion and exclusion criteria, 16 children were followed during a median time of 28 months (IQR 23-31 months); for a total of 116 visits, 87.5% (n = 14) of the patients developed a growth alteration. Five presented post-natal microcephaly, and among them, four presented malnutrition or low height. Six patients developed macrocephaly. Patients with a normal head circumference had normal neurodevelopment. Only one patient with microcephaly persisted with impairment of the neurodevelopment at the end of follow-up. All the patients with macrocephaly had normal neurodevelopment. Our study suggests that growth could be altered in infants with in utero Zika exposure. We found a high proportion of patients with overgrowth and macrocephaly. Future studies should consider endocrine follow-up of children born with in utero Zika exposure to explore these findings' possible aetiologies. We found a high proportion of growth alterations, particularly with overgrowth features and macrocephaly. Our study suggests that in addition to neurodevelopment impairment, growth could be altered in infants and children with in utero Zika exposure, even in those patients born without CZS.

Unsubstantiated belief in the diagnostic accuracy of the triad of abusive head trauma may lead to incorrect diagnoses of alleged abuse cases.

Unsubstantiated belief in the diagnostic accuracy of the triad of abusive head trauma may lead to incorrect diagnoses of alleged abuse cases.

Modeling Brain Overgrowth in Autism Using Human Pluripotent Stem Cells

16p11.2 copy number variation (CNV) is one of the most common genetic linkages of autism spectrum disorder (ASD). A large head size (referred to as macrocephaly) is common in 16p11.2 deletion syndrome, contributing to disproportionate enlargement in both gray and white matter volume. Individuals with ASD and macrocephaly have more severe behavioral and cognitive problems and are less responsive to standard therapeutic interventions, leading to poor prognoses relative to individuals with ASD and normal head circumferences.

The Neurobiology of Zika Virus: New Models, New Challenges.

The Zika virus (ZIKV) attracted attention due to one striking characteristic: the ability to cross the placental barrier and infect the fetus, possibly causing severe neurodevelopmental disruptions included in the Congenital Zika Syndrome (CZS). Few years after the epidemic, the CZS incidence has begun to decline. However, how ZIKV causes a diversity of outcomes is far from being understood. This is probably driven by a chain of complex events that relies on the interaction between ZIKV and environmental and physiological variables. In this review, we address open questions that might lead to an ill-defined diagnosis of CZS. This inaccuracy underestimates a large spectrum of apparent normocephalic cases that remain underdiagnosed, comprising several subtle brain abnormalities frequently masked by a normal head circumference. Therefore, new models using neuroimaging and artificial intelligence are needed to improve our understanding of the neurobiology of ZIKV and its true impact in neurodevelopment.

Delineation of the phenotype of MED17-related disease in Caucasus-Jewish families.

and Purpose: Postnatal progressive microcephaly, with seizures and brain atrophy (OMIM # 613668) is a rare disorder caused by a homozygous founder missense mutation c.1112T>C (p.L371P) in the MED17 gene on chromosome 11 that was identified in 2010 in Caucasus Jewish families. The present study aimed to delineate the phenotype and developmental outcomes in patients diagnosed with this mutation to date. We conducted a medical charts review to collect the clinical, laboratory and neuroimaging findings in patients from several unrelated families of Caucasus-Jewish origin, who were diagnosed with the same homozygous c.1112T>C MED17 mutation. The study cohort, including the previously reported patients, comprised 10 males and 5 females from 11 families. All subjects had at birth a normal head circumference, which steeply declined to -6SD within a few months. None of the patients achieved developmental milestones. All patients had progressive spasticity and were wheelchair bound due to spastic quadriplegia. All of them eventually developed profound intellectual disability. Epilepsy of varied severity was present in all patients. Most patients required enteral feeding due to aspirations. Eight patients died before puberty (age range 2-13 years). Brain MRI showed marked cerebral atrophy and early prominent cerebellar atrophy (vermian>hemispheres) accompanied by pontine ventral flattening. The founder c.1112T>C mutation in MED17 gene is expressed by a unique and homogeneous clinical phenotype with distinctive MRI findings. This mutation should be considered in patients of Caucasus-Jewish ancestry presenting with clinical features and a MRI pattern of progressive cerebral and cerebellar atrophy.

Association of term isolated microcephaly with mode of delivery and perinatal outcome - a retrospective case-control analysis

BackgroundWe aimed to evaluate the association of isolated fetal microcephaly measured by ultrasound prior to delivery at term with mode of delivery and perinatal outcome.MethodsA single-center retrospective study was conducted in 2012–2016. Fetal microcephaly was defined as head circumference > 2 standard deviations of the mean for gestational age and sex. We compared the obstetric, delivery, and outcome parameters of women in whom ultrasound performed up to 10 days prior to term delivery showed isolated fetal microcephaly (study group) or normal head circumference (reference group). Exclusion criteria were intrauterine fetal death, birthweight below the 10th percentile, and antepartum cesarean delivery for any indication.ResultsOf 3677 women included in the study, 26 (0.7%) had a late ultrasound finding of isolated fetal microcephaly. Baseline characteristics were similar in the two groups except for estimated fetal weight based on abdominal circumference and biparietal diameter, which was lower in the microcephaly group (3209.8 ± 557.6 vs. 2685.8 ± 420.8 g, p < .001). There was no significant between-group difference in rate of vaginal operative deliveries (11.7% vs 14.8%, respectively, p = 0.372). The study group had no intrapartum cesarean deliveries compared to 6.3% of the reference group (NS). Compared to controls, neonates in the study group were smaller (3323.2 ± 432.2 vs. 2957.0 ± 330.4 g, p < .001), with lower birthweight percentile (60.5 ± 26.5 vs. 33.6 ± 21.5%, p < .001) and were more often males (48.2 vs. 90.0%, p < .001). No significant differences were noted in perinatal outcomes between the groups, including admission to neonatal intensive care unit, intraventricular hemorrhage, 5-min Apgar score < 7, asphyxia, seizures, and sepsis.ConclusionsIsolated microcephaly in term fetuses is not advantageous for a vaginal delivery, nor does it does not pose a greater than normal risk of adverse perinatal outcome.

Microcephaly epidemic in Brazil: An earlier chapter

ObjectiveIdentify risk factors for microcephaly and evaluate historical trends of microcephaly and arboviruses to recognize patterns and anomalies that indicate the beginning of the microcephaly epidemic associated with Zika infection. MethodsThe head circumferences of 62,298 newborns was analyzed to identify cases of microcephaly between 2014 and 2017. We compared the groups of newborns with normal head circumferences and those with microcephaly to identify risk factors. A time series with the incidences of microcephaly was analyzed to assess the appearance of anomalous values in order to identify the beginning of the microcephaly epidemic. Data on the incidence of dengue fever was used to develop a control chart, aiming to identify changes in incidence and seasonality that could suggest the circulation of a new arbovirus. FindingsPremature newborns, children of mothers under 20 years of age and those born in 2014 and 2015 had a higher risk of microcephaly. Three quarters with anomalous incidences of microcephaly were identified, the first in 2014 and the others in 2015. The dengue fever epidemic curve in 2013 shows persistence of high incidences in atypical periods, suggesting the entry of a new virus in the 3rd and 4th quarters. ConclusionsThese findings represent epidemiological evidence of the existence of cases of Zika virus between the 2nd quarter of 2013 and the beginning of 2014. The results add new elements to understanding the Zika virus epidemic in the Americas.

The relationship between maternal vitamin D level with infants’ birth-weight, height and head circumference at birth

Introduction: Prevalence of vitamin D deficiency has been reported from all over the world since lower levels of vitamin D has been one of word’s problem in the 21st century; especially pregnant women are the most prominent one. Objectives: This study aims to investigate the relationship between mothers’ vitamin D level with infants’ birth-weight and head circumference. Patients and Methods: A cross-sectional study was conducted in the department of obstetrics and gynecology of Akbarabadi hospital during 2017-2018. Regarding two groups, infants’ three main characteristics including their weight, head circumference and height were studied. Results: The mean blood levels of vitamin D in mothers with normal-born neonates were 15.23 ± 7.14 (ng/ mL) and in the mothers who gave birth to low-birth weight were 10.02 ± 8.06 (ng/mL), which was significantly lower than the mothers of normal-weight infants (P=0.018). The mean blood levels of vitamin D in mothers who gave birth to a normal head circumference neonate were 16.07 ± 8.1 (ng/mL) and in mothers with infants’ head circumference of less than 33 cm, was 9.87 ± 7.57 (ng/mL), which was significantly lower from mothers of normal-head circumference infants (P=0.007). The serum levels of vitamin D in mothers with normal-height infants were 14.74 ± 7.52 (ng/mL) and in the mothers with a height of less than 47 cm were 15.17 ± 7.91 (ng/mL), that does not suggest any significant difference (P=0.341). The mean serum vitamin D level in mothers who had normal vaginal delivery was lower than those with cesarean delivery, however there was no significant difference (P=0.174). Conclusion: Nutrition improvement and prescribing vitamin D supplements can positively be effective in the way of curbing low-birth weight infants. Moreover, Exposure to sunlight and letting rays strike skin is essential for maintaining a healthy vitamin D status for girls and women.

12q14.3 microdeletion involving HMGA2 gene cause a Silver-Russell syndrome-like phenotype: a case report and review of the literature

BackgroundSilver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction and normal head circumference with consequent relative macrocephaly. Addictional findings are protruding forehead in early life, body asymmetry (of upper and lower limbs) and substantial feeding difficulties. Although several genetic mechanisms that cause the syndrome are known, more than 40% of patients with a SRS-like phenotype remain without an etiological diagnosis. In the last few years, different clinical reports have suggested that mutations or deletions of the HMGA2 gene can be responsible for a SRS-like phenotype in patients with negative results of the common diagnostic tests for this syndrome.Case presentationWe present a 3-year-old male patient with clinical diagnosis of Silver-Russell Syndrome (SRS) associated with a de novo heterozygous deletion of the long arm of the chromosome 12 (12q14.3) encompassing the HMGA2 gene.ConclusionsOur report confirms the etiological role of HMGA2 as a disease gene in the development of a SRS-like phenotype.

Genotype-phenotype correlation at codon 1740 of SETD2.

The SET domain containing 2, histone lysine methyltransferase encoded by SETD2 is a dual-function methyltransferase for histones and microtubules and plays an important role for transcriptional regulation, genomic stability, and cytoskeletal functions. Specifically, SETD2 is associated with trimethylation of histone H3 at lysine 36 (H3K36me3) and methylation of α-tubulin at lysine 40. Heterozygous loss of function and missense variants have previously been described with Luscan-Lumish syndrome (LLS), which is characterized by overgrowth, neurodevelopmental features, and absence of overt congenital anomalies. We have identified 15 individuals with de novo variants in codon 1740 of SETD2 whose features differ from those with LLS. Group 1 consists of 12 individuals with heterozygous variant c.5218C>T p.(Arg1740Trp) and Group 2 consists of 3 individuals with heterozygous variant c.5219G>A p.(Arg1740Gln). The phenotype of Group 1 includes microcephaly, profound intellectual disability, congenital anomalies affecting several organ systems, and similar facial features. Individuals in Group 2 had moderate to severe intellectual disability, low normal head circumference, and absence of additional major congenital anomalies. While LLS is likely due to loss of function of SETD2, the clinical features seen in individuals with variants affecting codon 1740 are more severe suggesting an alternative mechanism, such as gain of function, effects on epigenetic regulation, or posttranslational modification of the cytoskeleton. Our report is a prime example of different mutations in the same gene causing diverging phenotypes and the features observed in Group 1 suggest a new clinically recognizable syndrome uniquely associated with the heterozygous variant c.5218C>T p.(Arg1740Trp) in SETD2.

Motor development in non-microcephalic infants born to mothers with Zika Virus infection during pregnancy

ABSTRACT This cross-sectional study sought to evaluate motor development in infants exposed to ZIKV born with normal head circumference (HC). Thirty one children, distributed into two groups, participated in the study: 15 whose mothers were infected by ZIKV during pregnancy, born with HC from −1.9 to +2 Z-scores, adjusted for sex and gestational age (exposed group); and 16 randomly selected infants without known prenatal exposure to ZIKV, paired by sex and age (control group). Alberta Infant Motor Scale (AIMS) was used to evaluate gross motor development. We found no significant difference between the exposed and control groups. However, considering that AIMS is a screening test that assesses only the gross motor development and the small size of our sample, infants exposed to ZIKV during pregnancy should be continuously evaluated for different aspects of their development.

Silver-Russell syndrome. Clinical and etiopathological aspects of a model genomic imprinting entity.

Silver-Russell syndrome is characterized by asymmetrical intrauterine growth retardation, with normal head circumference and small, pointed chin, which results in a triangular face. It can also include body asymmetry, among other characteristics. Its global incidence is estimated at 1 in 30 000-100 000 births, even though this figure may be underestimated. In approximately 60 % of cases, a molecular cause can be identified, and the main one is hypomethylation of the paternal allele at the imprinting control region 1 located at 11p15.5-p15.4. It is necessary to make the diagnosis of this entity, exclude differential diagnoses, and know (epi)genotype-phenotype correlations in order to ensure an adequate follow-up, provide available therapeutic options, and offer a timely family genetic counseling. The objective of this article is to describe the current status of the Silver-Russell syndrome, a model of genomic imprinting disorder.

MON-054 First Report of Monozygotic Twins with Russell Silver Syndrome in China: Recombinant Growth Hormone Therapy and 3-Year Observation

BACKGROUND: Russell Silver syndrome (RSS) is a rare genetic condition that includes an important index of suspicion when a child presents with hemihyperthrophy. There are more than 400 cases described in the literature, but twin pairs with RSS have rarely been reported. Up to now only six monozygotic twin pairs have been described [1]. However, this has not been reported in east Asian population yet. Clinical Case: A 4 years and 9 months old monozygotic twin girl with a history of growth retardation was admitted to our hospital. The first impression of the patient was: poor growth, specific facial features, asymmetry of the lower and upper limbs for length and width. Detailed physical examination revealed a small triangular face with prominent forehead, micrognathia, lips with downturned corners, and fifth finger clinodactyly on bothhands. On admission into our hospital, the examination measured a weight of 9.0 kg (-4.9SD) and a length of 88.4 cm (-5.2SD). Anthropometrically she was classified as second grade malnutrition according to World Health Organization (WHO) charts. By contrast, her twin sister was physically and anthropometrically normal.Intrauterine growth retardation, postnatal growth retardation, normal head circumference and asymmetry of the body were the major criteria that made the clinical diagnosis of Russell-Silver syndrome. Confirmation of Russell-Silver syndrome was made based on clinical findings, birth history and results of molecular genetic testing showed hypomethylation of the paternal imprinting center 1 (IC1) of chromosome 11p15.5.Recombinant human growth hormone (rhGH) was administered by subcutaneous injection once daily, in the evening, at a dose of 0.05 mg/ kg/day. The check-up visits in the outpatient were held every three months, and the following issues were evaluated: response to treatment, tolerability, and laboratory test results, with particular emphasis on carbohydrate metabolism and bone age progression. Currently, after 28 months of rhGH treatment, the girl has grown 18 cm, reaching a body height of 106.5 cm (-3.2SD, ΔHt SDSCA: 2SD). Her current weight is 14.1 kg (-2.9SD, ΔWt SDSCA: 2SD). So far, no serious adverse events have been observed. Conclusion: This is the first case of monozygotic twin with Russell Silver syndrome reported in east Asian population. The possibility of rhGH treatment can be considered in cases of documented GH deficiency in patients with Russell Silver syndrome, under close endocrinic supervision.

SAT-LB17 Triplication of SHOX Downstream Region in Mild Short Stature

Deletions of the downstream flanking regions of the SHOX gene that contain conserved non-coding cis-regulatory DNA elements are a known cause of Leri-Weill dyschondrosteosis or idiopathic short stature (ISS). Functional and comparative genomic studies have demonstrated the existence of four CNE enhancers downstream of SHOX which have transcriptional activity, and a fifth has recently been suggested at approximately X:970,000. Duplications of these downstream regions have also been described in patients with ISS, although with a variable phenotype. We present a family with ISS and the first ever reported SHOX downstream triplication. The index case was a 12-year-old Caucasian female of unrelated parents, born with normal weight and length, and normal hearing/vision and development. At the age of 12, her height was -1.87 SD (-1.35 SD adjusted for parental height). Her growth chart showed a height on the 90th centile at birth, slowly crossing centiles for the first 5 years to the 2nd centile, which she then followed. She had normal proportions and head circumference, and no dysmorphic features apart from inverted nipples. Baseline investigations for short stature were normal, including IGF1, karyotype and celiac screen. Bone age was 1.5 year delayed. Family history: arthritis in the father, early menopause in the mother. Analysis of SHOX and its flanking regions was carried out using Multiplex Ligation-dependent Probe Amplification (MLPA) and direct sequencing of all coding exons. MLPA analysis showed a SHOX downstream triplication with a minimum size of 66kb (X:963670-1029779) and a maximum size of 428kb (X:899389-1327688). The size of the duplication was further defined using array comparative genome hybridization (ACGH) analysis which showed the minimum size to be ~325kb (X:907457-1232802). This triplication includes the proposed regulatory element at ~ X:970,000. The triplication was subsequently shown to be present in the proband’s mother and brother who also have mild ISS. Further analysis of these and other family members is ongoing. The triplication is of a single-sized fragment, and the fragment size is identical to one that has been seen in duplicated form in several other patients, increasing the likelihood that the triplicated fragments are in tandem. The precise mechanism of the pathogenic effect of the triplication is unknown, but it likely exerts a negative effect on SHOXtranscription, reducing its expression and ultimately resulting in SHOX haploinsufficiency. In conclusion, we describe a family with mild ISS and a downstream triplication of the proposed X:970,000 SHOX downstream regulatory element. This provides further evidence for this previously proposed regulatory element downstream of SHOX and adds additional proof that increased dosage of this regulatory element region is a cause of short stature.

MON-056 Rare X Chromosome Pericentric Inversion Associated with Ovotesticular Disorder of Sex Development

Ovotesticular disorder of sex development (OT-DSD) is a rare condition characterized by coexistence of ovarian and testicular parenchyma, in separate gonads or in the same gonad (ovotestis), in individuals with variable degrees of genital ambiguity. Karyotype may be 46,XX (60%), 46,XY (10%), or there may be sex chromosomes abnormalities, including mosaicism, chimerism and structural anomalies (30%). A genetic origin may be identified in some subjects with normal XX or XY karyotype, but most cases are of unknown origin. Apparently balanced chromosome rearrangements (translocations, insertions and inversions) may cause truncation, deletion, inactivation or over-expression of specific genes. We report on a case of OT-DSD associated with an X chromosome inversion. Case report: A 3-month old girl was referred due to atypical genitalia. She was born at term to a 42 years old G3P2A1 mother and her 45 years old unrelated husband with normal weight, length and head circumference. She had normal development, no associated health problems, and family history was unremarkable. Physical examination revealed a 3.1-cm phallus with chordee, scrotal hypospadias, partial penoscrotal inversion and a 0.5 cm3 right gonad palpable in the inguinal region; there were no associated dysmorphic features. At 1.5 months there were normal levels of FSH (3.09 IU/L) and LH (3.67 IU/L), and testosterone (155 ng/dL) was in the normal male range. Ultrasound revealed normal uterus and gonads were in the inguinal regions. Urethra-cystoscopy and vaginoscopy at 9 months revealed a urogenital sinus with high vaginal confluence. Laparoscopy and gonadal biopsies were also performed; the left gonad was an ovotestis with multiple ovarian follicles, while the right gonad was a testis. In both gonads the seminiferous tubules had only Sertoli cells. Karyotype revealed a pericentric X chromosome inversion, 46,X,inv(X)(p22.1q26)dn[20]. FISH on peripheral blood and cultured cells from the right gonad with probes for X (DXZ1) and Y (DYZ3) centromeres and SRY (Yp11.3 - 122 Kb) showed only two X chromosome signals. Array GH analysis (Cytoscan 750K, Affymetrix) showed a 1.3 Mb deletion distal to the short arm breakpoint (Xp22.31), which was reported as VOUS, and a 9 Mb region of LOH on chromosome 9. Discussion: Several cases of X pericentric inversion with different breakpoints have been reported; though phenotypes of female heterozygotes are often normal, early menopause, irregular menses, gonadal dysgenesis or sterility have been described. In this case, it is plausible that the genomic rearrangement could have affected long-range regulation of SOX3 (located in Xq27.1) resulting in ectopic expression of this gene in the bipotential gonad. In addition, the features detected in array GH may have a role in the phenotype. Different methods to determine the exact chromosomal breakpoints and copy number variations in this region will be required.

SAT-055 A De Novo 1p13.2 Deletion Related to Short Stature, Hypothyroidism and Mild Developmental Delay

Background: Chromosomal deletions may lead to variable phenotypic alterations, depending on which loci and genes are deleted. We present the case of a boy with a de novo 1p13.2 deletion which was diagnosed by array-CGH analysis. Clinical Case: A Greek boy, who was referred for evaluation of growth failure, was investigated. He was delivered at term by cesarean section, with normal birth weight (3.060 kg), birth length (51 cm) and head circumference (35.5 cm). There was no positive family history for short stature. Target height was on the 25th percentile. He presented with growth deceleration since the age of 12 months leading to stature lower than the 3rd percentile at the age of two years, while his weight was at the 3rd percentile. Macrocephaly was appreciated (53 cm, >95th percentile). Dysmorphic facial features resembling Noonan syndrome, such as frontal bossing, depressed nasal bridge and low-set ears were recognized. His motor development was normal. Laboratory examination revealed hypothyroidism and treatment with L-thyroxine was initiated. He had regular follow-ups at 6 months intervals. A mild delay in speech development and motor skills was appreciated. At the age of five years old, as his growth rate remained slow, growth hormone (GH) stimulation tests were performed. GH had a borderline normal peak of 9.9 ng/ml. IGF-1 levels were also within normal range (123.7 ng/ml). Magnetic Resonance Imaging (MRI) of the pituitary gland and the brain was normal. Array-CGH analysis detected a loss of approximately 800 Kb on chromosome 1p13.2; these alterations affect 8 genes in the OMIM database. The deleted segment was mapped at chr1: 115,186,092_115,977,647 region. The genomic coordinates are listed according to genomic build GRCh37/hg19. The genetic material analysis did not show the presence of a deficit in chromosomal region 1p13.2 (chr1: 115,186,092_115,977,647) in neither of the parents, indicating that this finding was created de novo. Conclusion: We describe a patient with a Noonan like phenotype, due to a 1p13.2 deletion. In the international literature and databases of Database of Genomic Variants and Database of Chromosomal Imbalance and Phenotype in Humans Using Ensemble Resources there are no reports of normal individuals or patients with a similar finding in chromosomal region 1p13.2. Regular follow up of the patient is needed in order to better understand the evolution of the phenotype.

Cardiopatia congênita: estado nutricional e proporcionalidade corporal ao nascimento

Introduction: Congenital heart diseases have a great impact on perinatal and infant mortality rates in Brazil. These are diseases that can lead to compromised growth and development of the child. The purpose of this study is to describe the nutritional condition and the corporal proportionality to the birth of children with congenital heart disease. Methods: A cross-sectional, retrospective study using data on the birth of children with congenital heart disease admitted to a cardiology service in the Northeast of Brazil between 2011 and 2014. The nutritional status was assessed by weight/age (W/A) indicators, length/age, weight/length, body mass index/age (BMI/A), ponderal index, cephalic perimeter. Results: A total of 117 patients were evaluated, being 60.7% male and 20.9% with cyanotic heart disease. It was found that 6.8% of the children were low birth weight. The nutritional indexes showed a 3.4% deficit in the W/A indicator, in weight/length 5.1%, for BMI/A 4.3% and length/age 7.8%. The ponderal index showed that 28.2% of the children were disproportionate at birth and 84.4% had a normal head circumference. Lower Z score values of W/A (p = 0.030) and BMI/A (p = 0.023) for cyanotic heart disease compared to other types of congenital heart diseases were observed in our study. Conclusions: Children with congenital heart disease had relatively preserved nutritional status at birth, with prevalence of nutritional disorders similar to those described in the literature.

Karakteristik Anak Berkebutuhan Khusus di Klinik Tumbuh Kembang Pelangi Kasih, Pontianak, Tahun 2013-2017

Tujuan: Mengetahui gambaran karakteristik anak berkebutuhan khusus yang datang ke klinik Tumbuh Kembang Pelangi Kasih, Pontianak, tahun 2013 – 2017.Metode: Penelitian deskriptif, potong lintang, dengan penelusuran data rekam medis anak berkebutuhan khusus yang konsultasi ke Klinik Tumbuh Kembang Pelangi Kasih pada tahun 2013 hingga 2017. Hasil: Didapatkan total 302 data rekam medis lengkap, 212 anak laki-laki. Anak yang paling banyak dibawa konsultasi adalah anak urutan pertama sebanyak 195 anak. Kekuatiran orang tua terhadap perkembangan anaknya rata-rata dimulai di usia 1 tahun 9 bulan. Keterlambatan konsultasi terjadi sekitar 1 tahun 5 bulan. Anak banyak dibawa orang tua untuk konsultasi perkembangan atas inisiatif sendiri dan rujukan keluarga/teman sebesar 64,9%, jauh lebih tinggi dibandingkan rujukan tenaga professional (dokter, guru, dan dokter anak). Keluhan utama terutama adalah keterlambatan bicara, sebesar 80,8%. Lebih banyak anak yang tidak memiliki faktor risiko gangguan perkembangan (64,6%). Sebagian besar anak memiliki status gizi normal dengan lingkar kepala normal.Kesimpulan: Perlu adanya skrining perkembangan rutin untuk meningkatkan kesadaran terhadap gangguan perkembangan pada bayi, terutama pelatihan untuk meningkatkan kemampuan tenaga profesional dalam deteksi dini gangguan perkembangan pada bayi dan anak.

Neurological outcomes of congenital Zika syndrome in toddlers and preschoolers: a case series

Congenital Zika syndrome causes a spectrum of neurological symptoms with varying effects on function that require different therapeutic strategies. To date, this spectrum of effects and its clinical implications have not been completely described. We describe the neurological examination findings in toddlers and preschoolers, including predominant symptom complexes and comorbidities. This study is a case-series neurological evaluation of 75 children with congenital Zika syndrome in Campina Grande, Brazil. The study is part of a cohort of children with congenital Zika syndrome that started in 2015 and is still ongoing. Children with Zika virus infection detected during pregnancy (mothers exhibited rash and were followed and diagnosed by fetal ultrasound abnormalities or RT-PCR) or through microcephaly screening after birth, using Intergrowth 21 guidelines, were selected by laboratory and radiological criteria. Children were examined during a 10-day period in September, 2018, and underwent neurological interview, examination, and assessment of functional outcomes and comorbidities. Children were divided in groups of predominant corticospinal or neuromuscular clinical signs and the associations between these groups and clinical comorbidities were assessed. All of the children recruited to the study from Nov 29, 2015 to Nov 30, 2017 had imaging correlates of congenital Zika syndrome. Children were assigned to groups depending on the signs exhibited, either corticospinal or neuromuscular, with or without dyskinetic signs. 75 children completed the evaluation, 38 (51%) girls and 37 (49%) boys. Median age was 33 months (range 26-40 months; IQR 29-34). Microcephaly was present at birth in 56 (75%) children, and 19 (25%) children were born with normal head circumference, 15 of whom later developed microcephaly. Neurological examination grouped four children as having isolated dyskinetic signs, 48 children were assigned to the corticospinal group and 23 into the neuromuscular group. Dyskinetic findings were present in 30 (40%) children, either alone (four [5%]) or combined with corticospinal (19 [40%] of 48) or neuromuscular (seven [30%] of 23) findings. Comorbidities were highly prevalent, and the neuromuscular group had worse functional outcomes, evaluated by gross motor function (p=0·026), manual abilities (p=0·0013), and communication function (p<0·0005) classification scales, than the corticospinal group, whereas pneumonia (p<0·0005) and urinary tract infections (p<0·0005) were more frequent in the corticospinal group. Cortical hyperexcitability was supported by several clinical correlates, such as early onset epilepsy, persistence of primitive reflexes, and dystonia. We describe distinct neurological profiles in the congenital Zika syndrome spectrum, with functional outcomes tending to correlate with these groups. The clinical division of children based on the disease signs proposed here is supported by the literature on central and peripheral nervous system pathology in congenital Zika syndrome. The high prevalence of dyskinetic symptoms merits special attention. Brazilian National Council for Scientific and Technological Development and by the Coordination for the Improvement of Higher Education Personnel.