Neonatal Presentation Research Articles

Neonatal presentation of Joubert syndrome

Joubert syndrome is a rare genetic disorder with autosomal recessive or rarely X-linked recessive inheritance. Authors are reporting a case of a newborn girl with Joubert syndrome who presented with respiratory distress, hypotonia, hyporeflexia, abnormal eye movements, and facial dysmorphism. Brain MRI revealed vermian hypoplasia, “molar tooth sign” with “bat wing appearance” of the fourth ventricle, deepened interpeduncular fossa, and elongated superior cerebellar peduncles. The clinical diagnosis of this syndrome is difficult due to its variable presentation and non-specific presentation. Magnetic Resonance Imaging (MRI) has an important role in the diagnosis of Joubert syndrome. This not only helps in early diagnosis but also helps in appropriate counseling and proper rehabilitation of the baby.

Perinatal features of Prader-Willi syndrome: a Chinese cohort of 134 patients

BackgroundPrader-Willi syndrome (PWS) is a rare and complex genetic disorder caused by lacking expression of imprinted genes on the paternally derived chromosome 15q11-q13 region. This study aimed to characterize the perinatal features of 134 Chinese individuals with PWS.MethodsThis study included the patients of a PWS registry in China. Anonymous data of 134 patients were abstracted. Perinatal and neonatal presentations were analyzed, and compared between the two PWS genetic subtypes. We also compared the perinatal features of PWS patients with the general population and other previous reported large cohorts from France, UK and USA.ResultsThis study included 134 patients with PWS (115 patients with 15q11-q13 deletion and 19 with maternal uniparental disomy). Higher mean maternal age was found in this cohort (30.5 vs. 26.7), particularly in the maternal uniparental disomy (UPD) group (36.0 vs. 26.7) comparing with the general population. 88.6% of mothers reported a decrease of fetal movements. 42.5 and 18.7% of mothers had polyhydramnios and oligohydramnios during pregnancy, respectively. 82.8% of the patients were born by caesarean section. 32.1% of neonates had birth asphyxia, 98.5% had hypotonia and 97.8% had weak cry or even no cry at neonatal period. Feeding difficulty existed in 99.3% of the infants, 94.8% of whom had failure to thrive. 69.4% of the infants ever used feeding tube during hospitalization, however, 97.8% of them discontinued tube feeding after discharge. Maternal age and pre-pregnancy weight were significantly higher in the UPD group (both P < 0.05).ConclusionsDifferential diagnosis of PWS should be highlighted if infants having following perinatal factors including polyhydramnios, decreased intrauterine fetal movements, caesarean section, low birth weight, feeding difficulty, hypotonia and failure to thrive. Higher maternal age may be a risk factor of PWS, especially for UPD. Further studies are needed for elucidating the mechanism of PWS.

Obstetrical and neonatal outcomes after successful external cephalic version relative to those after spontaneous cephalic presentations

ObjectiveExternal cephalic version (ECV) is a procedure during which the fetus is rotated from breech or transversal to cephalic presentation. Our aim was to assess the outcomes of successful ECV in terms of obstetrical and immediate neonatal outcomes relative spontaneous cephalic presentation. MethodsWe performed a retrospective single-center observational study from January 2007 to December 2017. All included participants benefited from trial of labor with delivery of the fetus in cephalic presentation. They were divided into two groups depending on whether an ECV had been successfully performed or cephalic presentation was spontaneous. ResultsThe cephalic presentation after ECV and spontaneous cephalic groups comprised 55 and 244 patients, respectively. The two groups differed significantly in terms of the proportion of induced labor (20 [36.4 %] and 56 [22.9 %], p = 0.04), use of oxytocin during labor (31 [56.4 %] and 100 [49.9 %], p = 0.04), duration of labor (342 ± 183 min and 279 ± 140 min, p = 0.008), spontaneous delivery (38 [69.1 %] and 199 [81.5 %], p = 0.04), intrapartum cesarean section (9 [16.4 %] and 16 [6.6 %], p = 0.02), occiput-posterior variety at birth (20 [36.4 %] and 56 [22.9 %], p = 0.04), and brace umbilical positioning at birth (3 [5.4 %] and 2 [0.8 %], p = 0.04), respectively. There were no significant intergroup differences in terms of APGAR score, cord arterial pH/lactates, or reanimation/intensive care admission. ConclusionA successful ECV does not seem to guaranty an identical labor progress and obstetrical outcome as spontaneous cephalic presentations. Immediate neonatal state, on the other hand, seems unaffected by a history of ECV.

206 Contemporary Outcomes in Neonates Presenting With Congenital Complete Heart Block Presenting as Neonates- a 22 Year Series

Congenital complete heart block (CHB) is a rare condition, with a documented UK incidence of 1 in 50,000 live births. In this study, we aim to identify risk factors associated with morbidity and mortality in neonates presenting with CHB to the Sydney Children’s Hospital Network. Retrospective analysis of the clinical notes of neonates less than 29 days of age; presenting with CHB over the last 22 years performed. Of 2,853,111 registered live births in NSW over 22 years, 41 neonates presented with CHB (1 in 69,000). Mean gestational age was 36 weeks with mean birth weight 2.5 kg. Maternal immunological diagnosis (MID) was present in 25/41(61%), complex congenital heart defect (CCHD) in 6/41(15%), and 10(24%) had neither. Antenatal data were available in 35/41. Bradycardia was detected in 34/35 fetuses (97%), with diagnosis of CHB in 31/35(89%). Antenatal hydrops diagnosed in 6/35(17%); 5/6(83%) had MID and 3/6(50%) died. Deaths: 7/41 infants (17%) died. Of these 7, 4(57%) had MID and 3(43%) had CCHD. Thus, 4/25(16%) infants with MID died and 3/6(50%) with CCHD died. Out of the 7 who died, 3/7(42%) had ventricular dysfunction at birth with 1/3 having endocardial fibroelastosis. Pacemaker implantation: 27/41(66%) required insertion of permanent pacemaker in the neonatal period. 2/41(4%) died before pacemaker insertion. The minimal incidence of neonatal CHB in NSW is 1/69,000. Risk factors for mortality are the presence of antenatal hydrops, ventricular dysfunction at birth and CCHD. Two thirds of neonates required pacing in the first month of life.

Smith–magenis syndrome. A unique neonatal presentation among the Arab population

Smith–Magenis Syndrome (SMS) is a rare multisystem genetic disorder caused by a heterozygous deletion of or a heterozygous pathogenic variant in RAI1 on chromosome 17p11.2. characterized by the variable intellectual deficit, sleep disturbance, brachycephaly, midface hypoplasia, prognathism, hoarse voice, speech delay with or without hearing loss, psychomotor and growth retardation, cutaneous features, and behaviour problems. Our reported case is a term newborn diagnosed antenatally in the feto-maternal unit to have large multi-cystic dysplastic left kidney and unilateral cerebralventriculomegaly. The genetic disorder was suspected due to symmetric IUGR and dysmorphic features. Chromosomal micro-array confirmed the diagnosis of Smith-Magenis Syndrome.MRI brain confirmed Dandy-Walker spectrum malformation. Ultrasound abdomen showed left multi-cystic dysplastic kidney. Smith-Magenis Syndrome is usually diagnosed in childhood and little is known about its presentation in neonates especially in the Arab population. Our patient presented with Intra-cranial haemorrhage, seizures, thrombocytopenia, feeding difficulty, hypoglycemia and acute kidney injury; which all resolve before discharge.

Congenital laryngeal saccular cyst leading to stridor in a newborn: Think beyond laryngomalacia

Laryngomalacia is the most common congenital anomaly of the larynx leading to stridor in newborns. However, laryngeal cyst, although rare, should also be considered in the differential diagnosis of stridor. Hence, every newborn with stridor should undergo flexible/rigid endoscopic evaluation of the airway so that these rare entities are not missed, as its early recognition and proper treatment are essential because it can cause life-threatening airway obstruction. We describe a newborn presenting to us with stridor and severe respiratory distress since birth, who was successfully treated with no recurrence, with transoral microscopic complete excision of the laryngeal saccular cyst. We emphasize the importance of a good clinical history along with endoscopic evaluation of the airway in every neonate presenting with stridor with an unexpected evolution to determine the causal lesion.

Ecthyma gangrenosum in a neonate

Ecthyma gangrenosum (EG) is pathognomonic of invasive Pseudomonas infection or septicemia. It is characterized by pustules that rapidly evolve into hemorrhagic blister with central necrosis with the surrounding erythema. It is more often seen in immunocompromised patients but can be seen in healthy neonate also. We report the case of a 4-day-old neonate presenting with Pseudomonas bacteremia and EG.

Vein of Galen aneurysmal malformation in a neonate presenting with congestive heart failure

Vein of Galen aneurysmal malformation in a neonate presenting with congestive heart failure

Clinical and Imaging Findings of Neonatal Seizures Presenting as Diffuse Cerebral White Matter Abnormality on Diffusion-Weighted Imaging without any Structural or Metabolic Etiology.

PurposeSome patients with neonatal seizures show diffuse, symmetric diffusion-restricted lesions in the cerebral white matter. The aim of this study was to describe clinical and imaging findings of patients with neonatal seizures who had diffuse, symmetric diffusion-restricted lesions without any structural or metabolic etiology.Materials and MethodsA total of 56 neonates aged less than 1 week underwent brain magnetic resonance imaging (MRI) for evaluation of seizures from November 2008 to February 2017. After excluding 43 patients, 13 patients showed diffuse white matter abnormality on diffusion-weighted imaging. Initial and follow-up clinical and MRI findings were analyzed retrospectively.ResultsAll 13 patients were born at full term. Among the ten patients who underwent a stool test for viruses, six were positive for rotavirus and one for astrovirus. MRI revealed diffuse, symmetric diffusion-restricted lesions distributed along the cerebral white matter, thalami, and midbrain variably.ConclusionDiffuse, symmetric diffusion-restricted lesions involving the cerebral white matter can be seen in patients with neonatal seizures without any structural or metabolic etiology. Rotavirus is commonly but not exclusively detected in these patients. Nevertheless, viral infection-associated encephalopathy should be considered for patients with characteristic clinical and MRI findings.

Aplasia cutis congenita with hypocalvaria in a neonate

We report a neonate presenting with a large scalp defect with hypoplasia of underlying frontal and parietal bones. It fits into the description of a severe form of aplasia cutis congenital with hypocalvaria.

Phenotypic spectrum and genetics of SCN2A-related disorders, treatment options, and outcomes in epilepsy and beyond.

Pathogenic variants in the SCN2A gene are associated with a variety of neurodevelopmental phenotypes, defined in recent years through multicenter collaboration. Phenotypes include benign (self-limited) neonatal and infantile epilepsy and more severe developmental and epileptic encephalopathies also presenting in early infancy. There is increasing evidence that an important phenotype linked to the gene is autism and intellectual disability without epilepsy or with rare seizures in later childhood. Other associations of SCN2A include the movement disorders chorea and episodic ataxia. It is likely that as genetic testing enters mainstream practice that new phenotypic associations will be identified. Some missense, gain of function variants tend to present in early infancy with epilepsy, whereas other missense or truncating, loss of function variants present with later-onset epilepsies or intellectual disability only. Knowledge of both mutation type and functional consequences can guide precision therapy. Sodium channel blockers may be effective antiepileptic medications in gain of function, neonatal and infantile presentations.

Successful Treatment of Neonatal Herpes Simplex Infection Presenting as Fulminant Hepatitis with Acyclovir and Peritoneal Dialysis

Successful Treatment of Neonatal Herpes Simplex Infection Presenting as Fulminant Hepatitis with Acyclovir and Peritoneal Dialysis

Clinical, genetic, and radionuclide characteristics of the focal form of congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a severe disease with a high risk of complications including neurological deficit. Persistent hypoglycemia in patients with focal form of CHI can not be managed with medical treatment in 96.4% of cases, what subsequently leads to surgical treatment. Currently, there is a lack of information regarding patients with focal form of CHI. This study is aimed at finding better approaches for diagnosis and treatment of patients with focal form of CHI. To study clinical, genetic and PET/CT findings of the focal form of CHI in Russian group of patients. The observational research included all patients with a histologically confirmed focal form of CHI, who were admitted to Endocrinology Research Centre during the period from January 2008 to January 2019. A statistical analysis of clinical data, genotype, and positron emission tomography (PET) with 18F-dihydroxyphenylalanine (18F-DOPA) was performed. The median follow-up was 18 months. The study included 31 patients with focal CHI (14 boys, 45.2%). All patients had a neonatal presentation of the disease and demanded high levels of continuous glucose infusion to maintain euglycemia. The difference between the age of hypoglycemia presentation and the age of diagnosis ranged from 1 day to 3.9 months. In all cases, diazoxide was found to be ineffective. However, in 9 patients, it was possible to withdraw continuous glucose infusion and maintain euglycemia using octreotide in the preoperative period. A molecular genetic study allowed us to detect diverse pathogenic variants in ABCC8 and KCNJ11 genes in 30 patients. According to PET data with 18F-DOPA, the pancreatic index (PI) varied widely from 1.16 to 3.59. After partial resection of the pancreatic region with insulin hypersecretion, all patients showed complete recovery. The focal form of CHI is a severe condition with high prevalence of neurological complications. For preoperative diagnosis of the morphological form of the disease, it is necessary to conduct genetic analysis and radionuclide studies. Solely evaluation of mathematical parameters in 18F-DOPA PET without taking into account the visual data and the results of genetic analysis does not allow establishing the robust diagnosis. Timely diagnosis, identification of risk factors, and prevention of complications of persistent hypoglycemia are important tasks for clinicians.

Multiple Congenital Anomalies in a Patient with Interstitial 6q26 Deletion

We report a preterm male neonate presenting with a lumbosacral meningomyelocele, type II Arnold Chiari malformation, hypoplasia of the aortic arch, bicuspid aortic valve, ventricular septal defect, secundum atrial septal defect, multicystic dysplastic kidney, and hydronephrosis. Analysis with whole genome SNP microarray revealed an interstitial deletion of about 237 kb in chromosome 6q26. Long contiguous stretches of homozygosity (>3 Mb) were seen in 18 chromosomes with a total genomic size of 219 Mb. The phenotype seen in our patient has not been reported in association with the genes in the homozygous regions. However, our patient shares many phenotypic features with other reported cases that have shown a deletion in the same region of chromosome 6.

Neuroimaging Spectrum of Inherited Neurotransmitter Disorders.

Inherited neurotransmitter disorders are rare neurometabolic conditions which encompass genetic disorders of neurotransmitter metabolism or transport. The clinical manifestations of these rare disorders are often nonspecific, ranging from encephalopathies and seizures to movement disorders. As a consequence, neurotransmitter disorders are underrecognized and often misdiagnosed. Accurate and timely diagnosis is, however, of utmost importance, given the availability of therapeutic strategies. A high index of clinical suspicion and familiarity with the neuroimaging phenotypes is therefore crucial. While the imaging features of various neurotransmitter disorders often overlap and are nonspecific, imaging can be helpful in providing useful clues to guide the diagnostic algorithm for uncommon conditions in a neonate presenting with nonspecific neurological symptoms. In this review paper, we aim to bring together current knowledge of neuroimaging phenotypes associated with inherited (primary) disorders of neurotransmitter biosynthesis. Magnetic resonance imaging phenotypes of disorders of monoamine biosynthesis, primary cerebral folate deficiency, disorders of pyridoxine metabolism, disorders of gamma-aminobutyric acid metabolism, nonketotic hyperglycinemia (glycine encephalopathy), disorders of serine biosynthesis, and cerebral creatine deficiency syndrome will be discussed and illustrated with case examples.

P.235Clinico-pathological characterisation of CACNA1S related congenital myopathy in children

Mutations in the CACNA1S gene were recently identified as a new cause of congenital myopathy (CM). To date only a few cases have been described, with limited phenotypic data. We report the clinical, pathological and radiological phenotype in five children with genetically confirmed CACNA1S-CM. →Patients were referred to our national highly specialised service for CM at The Dubowitz Neuromuscular Centre, UK. We conducted retrospective case note analysis. Two patients had recessive inheritance and three autosomal dominant. →Four of five patients (age range 7-18 years) had severe neonatal presentation with foetal akinesia, weakness, hypotonia, contractures, feeding difficulties and respiratory compromise. The 5th patient presented with motor delay in infancy. All five patients had proximal predominant, bulbar and facial weakness but showed spontaneous improvement over time. Ophthalmoplegia was noted in three. Two patients remain non-ambulant. Two developed scoliosis. Two are on nocturnal non-invasive ventilation initiated at age of 5 months and 7 years. All apart from one required nasogastric/gastrostomy feeding up until 2-5 years of age, but all were able to feed orally from age 5 years. One patient had clear history of periodic weakness well responding to Acetazolamide. Two children reported fatigue and limited endurance but no abnormalities of neuromuscular transmission were detected. All muscle biopsies showed fibre size variation and marked slow fibre predominance. Additional findings included mild central nucleation, few central cores and focally accentuated pseudo-dystrophic changes. Three out of the five patients had abnormal lower limb muscle MRI but with no specific muscle pattern. →CACNA1S related myopathy is a recently described form of congenital myopathy and should be considered in cases of undiagnosed dominant and recessive congenital myopathies with phenotypical features presented above.

Cell surface antigens of neonatal monocytes are selectively impaired in basal expression, but hyperresponsive to lipopolysaccharide and zymosan

Toll-like receptors (TLRs) are important components of the innate immune system, but how neonatal TLR-mediated immune responses differ from those of adults is unknown. We aimed to clarify the TLR-mediated expression profiles of cell surface antigens related to antigen presentation in neonates. CD14-positive monocytes were isolated from human cord blood and adult peripheral blood and then stimulated with lipopolysaccharide (LPS; TLR4 agonist) or zymosan (TLR2/6 agonist) or left unstimulated. Expression levels of the surface antigens major histocompatibility (MHC)-class II, CD80, CD86, CD11b, CD11c, CD14, and CD16 were then evaluated by flow cytometry. Cord blood CD14+CD16high monocytes (CBM) showed significantly lower basal levels of MHC-class II, CD80, and CD11b than adult blood CD14+CD16intermediate monocytes (ABM) (P < 0.01, P < 0.001, P < 0.001, respectively). LPS stimulation enhanced expression of MHC class II, CD80, and CD11b significantly more in CBM than in ABM (P < 0.001, P < 0.01, P < 0.01, respectively), resulting in levels that did not differ between CBM and ABM. Zymosan stimulation also enhanced expression of MHC class II, CD86, CD11b, and CD11c significantly more in CBM than in ABM (P < 0.001, P < 0.01, P < 0.001, P < 0.01, respectively), resulting in levels of CD86 and CD11c that did not differ in CBM and ABM. However, MHC class II, CD80, and CD11b remained significantly higher in ABM than in CBM (P < 0.05, P < 0.01, P < 0.05, respectively). These data indicate that CBM and ABM have distinct phenotypes and responses to stimulation.

Hereditary protein C deficiency caused by novel compound heterozygous mutants in a Chinese pedigree: A case report

Purpura fulminans (PF) is a neonatal presentation of homozygous or compound heterozygous protein C (PC) deficiency; infants who are diagnosed with it are determined to have a major defect in coagulation regulation which is associated with undetectable levels of PC. We report a pedigree who suffered from the hereditary PC deficiency with compound heterozygous mutants; genetic analysis revealed compound heterozygous mutations of 262 G > T(Asp88Tyr) and 400 + 5G > A that were identified in the proband; moreover, Asp88Tyr and 400 + 5G > A were also detected in the father and the mother, respectively. A bioinformatics analysis revealed 262 G > T is probably damaging, and structural analysis indicated a possible mechanism for the functional impairment of PC in this pedigree.

Exstrophy of Cloaca Sequence (Oeis Complex) With Multiple Cardiac Malformations

Omphalocele, Exstrophy, Imperforate anus, Spinal defects (OEIS) complex is the most severe birth defect within the exstrophyepispadias&nbsp;complex. There is exstrophy of the cloaca, failure of fusion of the genital tubercles and pubic rami, omphalocele and&nbsp;incomplete development of the lumbosacral vertebrae with hydromyelia. The diagnosis of OEIS complex mainly relies on sonographic&nbsp;findings. Our case presented with microcephaly, omphalocele, syndactyly, hydromyelia, imperforate anus, single cloacal opening,&nbsp;bifid clitoris, prominent unfused pubic rami and left renal agenesis. In addition, multiple severe cardiac malformations were found on&nbsp;echocardiography. Prognosis is poor when the OEIS complex is compounded by life-threatening malformations. We report a rare case&nbsp;of a preterm neonate presenting with features of OEIS complex with multiple cardiac malformations.

Liver Pathology in Mitochondrial Complex I Deficiency from Bi-Allelic Mutations in NDUFS2: A Report of Findings at Autopsy

Background: Mitochondriopathies are a heterogeneous group of genetic disorders with a wide array of symptomatology, organ system involvement, and inheritance patterns. Neonatal presentation can be fatal with neuromuscular dysfunction, lactic acidosis and hepatic failure. Historic literature has numerous phenotypic illustrations; however, genotypic correlation is limited. With improved testing methods, genotype–phenotype correlation is now increasingly feasible as demonstrated herein. Case Report: We present liver pathology findings in an infant who expired with a diagnostic suspicion of a mitochondrial disorder. Postmortem hepatocyte hypereosinophilia with microvesicular steatosis associated with ultrastructural findings of mitochondrial hyperplasia supported a mitochondriopathy. Genetic testing eventually confirmed mitochondrial complex I deficiency from bi-allelic mutations in NDUFS2. Conclusions: Morphologic attributes can assist in diagnosis of mitochondriopathies before specific genetic testing results are available. This case also highlights that diagnostic information can be gained from ultrastructural examination of postmortem liver tissue.