Divergent neurodevelopmental profiles of very-low-birth-weight infants.

BACKGROUND: Advanced perinatal medicine has decreased the mortality rate of preterm infants. Long-term neurodevelopmental outcomes of very-low-birth-weight infants (VLBWIs) remain to be investigated. METHODS: Participants were 124 VLBWIs who had in-hospital birth from 2007 to 2015. Perinatal information, developmental or intelligence quotient (DQ/IQ), and neurological comorbidities at ages 3 and 6 years were analyzed. RESULTS: Fifty-eight (47%) VLBWIs received neurodevelopmental assessments at ages 3 and 6 years. Among them, 15 (26%) showed DQ/IQ <75 at age 6 years. From age 3 to 6 years, 21 (36%) patients showed a decrease (≤-10), while 5 (9%) showed an increase (≥+10) in DQ/IQ scores. Eight (17%) with autism spectrum disorder or attention-deficit hyperactivity disorder (ASD/ADHD) showed split courses of DQ/IQ, including two with ≤-10 and one with +31 to their scores. On the other hand, all 7 VLBWIs with cerebral palsy showed DQ ≤35 at these ages. Magnetic resonance imaging detected severe brain lesions in 7 (47%) of those with DQ <75 and 1 (18%) with ASD/ADHD. CONCLUSIONS: VLBWIs show a broad spectrum of neurodevelopmental outcomes after 6 years. These divergent profiles also indicate that different risks contribute to the development of ASD/ADHD from those of cerebral palsy and epilepsy in VLBWIs. IMPACT: Very-low-birth-weight infants (VLBWIs) show divergent neurodevelopmental outcomes from age 3 to 6 years. A deep longitudinal study depicts the dynamic change in neurodevelopmental profiles of VLBWIs from age 3 to 6 years. Perinatal brain injury is associated with developmental delay, cerebral palsy and epilepsy, but not with ASD or ADHD at age 6 years.

Utility of Positional Instillation of Contrast Cystography for Diagnosing Occult Vesicoureteral Reflux in Children: A Report of Two Cases.

Positional instillation of contrast (PIC) cystography is effective for detecting occult vesicoureteral reflux (VUR), which can not be revealed by standard voiding cystourethrography (VCUG). We experienced two cases of young female patients; one had repeated urinary tract infection with a negative VUR on standard VCUG, and the other had findings suggestive of reflux hydronephrosis and intolerance of standard VCUG. They underwent PIC cystography, and occult VUR was detected in both cases. Both were successfully treated with simultaneous endoscopic injection therapy with dextranomer/hyaluronic acid. PIC cystography is useful for detecting occult VUR in children with negative VUR findings on standard VCUG or who are unable to tolerate standard VCUG.

Long surviving classical Menkes disease treated with weekly intravenous copper therapy.

Menkes diseases (MD) is an X-linked recessive neurodegenerative disorder of copper metabolism, characterized by progressive multisystemic involvement. Death in the early childhood is usually observed in classical patients. Although a definite cure has not been established, copper replacement therapy administered parenterally may modify the severity of MD and permitted survival into adolescence. Subcutaneous copper-histidine supplementation is the current choice of therapy, and long-term administration is not desirable because of the expected nephrotoxicity. We report here the case of a 29-year-old male with MD who tolerated long-term intravenous copper therapy initiated at 2 months. Molecular analysis revealed hemizygous deletion mutation of ATP7A previously reported in classical MD. Although neurodevelopement is poor, no major event of central nervous system is observed, and he enjoys a good social life by interacting using gestures. Optimum management is unknown, and closed follow-up is mandatory for clarification of this phenotype.

De novo KCNT1 mutations in early-onset epileptic encephalopathy.

KCNT1 mutations have been found in epilepsy of infancy with migrating focal seizures (EIMFS; also known as migrating partial seizures in infancy), autosomal dominant nocturnal frontal lobe epilepsy, and other types of early onset epileptic encephalopathies (EOEEs). We performed KCNT1-targeted next-generation sequencing (207 samples) and/or whole-exome sequencing (229 samples) in a total of 362 patients with Ohtahara syndrome, West syndrome, EIMFS, or unclassified EOEEs. We identified nine heterozygous KCNT1 mutations in 11 patients: nine of 18 EIMFS cases (50%) in whom migrating foci were observed, one of 180 West syndrome cases (0.56%), and one of 66 unclassified EOEE cases (1.52%). KCNT1 mutations occurred de novo in 10 patients, and one was transmitted from the patient's mother who carried a somatic mosaic mutation. The mutations accumulated in transmembrane segment 5 (2/9, 22.2%) and regulators of K(+) conductance domains (7/9, 77.8%). Five of nine mutations were recurrent. Onset ages ranged from the neonatal period (<1 month) in five patients (5/11, 45.5%) to 1-4 months in six patients (6/11, 54.5%). A generalized attenuation of background activity on electroencephalography was seen in six patients (6/11, 54.5%). Our study demonstrates that the phenotypic spectrum of de novo KCNT1 mutations is largely restricted to EIMFS.

Early onset of moyamoya syndrome in a Down syndrome patient with the genetic variant RNF213 p.R4810K.

Moyamoya syndrome is a unique progressive occlusive cerebrovascular disease that predisposes affected patients to stroke. We describe the case of a 2-year-old girl presenting with early onset of moyamoya syndrome with concurrent Down syndrome. Genetic testing revealed a heterozygous missense variant of RNF213. RNF213 was recently identified as the first susceptibility gene for moyamoya disease in patients with no known associated risk factors. The reported median age at the onset of idiopathic moyamoya disease with a heterozygous RNF213 risk variant is 7 years, while, the average age at onset of moyamoya syndrome in Down syndrome is 7-16 years. Down syndrome and RNF213 variant contribute to the development of moyamoya vasculopathy in different ways. Although the underlying mechanism is not fully understood, an additive effect was observed with the early-onset seen in this patient. Little is known about the potential association between RNF213 and moyamoya syndrome. Based on these observations, we hypothesize that the RNF213 risk variant has a modifier effect in steno-occlusive vasculopathy, even in medical conditions known to be associated with moyamoya syndrome.

A case of pontine tegmental cap dysplasia with comorbidity of oculoauriculovertebral spectrum.

Pontine tegmental cap dysplasia (PTCD) is a newly described brainstem malformation with distinct neuroimaging findings, characterized by a flattened ventral pons, cerebellar vermal hypoplasia and vaulted pontine tegmentum that forms a "caplike" or "beaklike" bulge projecting into the fourth ventricle. We describe a 3-month-old infant male who presented with typical neuroradiological findings as well as clinical features of PTCD. Notably, he manifested multiple anomalies with left ocular and facial hypoplasia, bilateral sensorineural hearing loss and rib and vertebral anomalies. Oculoauriculovertebral spectrum (OAVS) was thus considered to be an accompanying phenotype of this patient. The unique comorbidity seen in this patient suggests that PTCD and OAVS may partly share a common mechanism in their pathogenesis.

Neonatal bacterial meningitis caused by Streptococcus gallolyticus subsp. pasteurianus.

This report describes a case of neonatal bacteraemia and meningitis due to Streptococcus gallolyticus subsp. pasteurianus. Based on the identification kit results, this species may have been reported as Streptococcus bovis or S. bovis biotype II. The accurate identification of this organism is mandatory for evaluating the aetiology of neonatal meningitis.

Fatal visceral varicella-zoster virus infection without skin involvement in a child with acute lymphoblastic leukemia.

A 5-year-old girl with acute lymphoblastic leukemia in remission suffered from fatal visceral varicella-zoster virus (VZV) infection after the oral administration of a high-dose dexamethasone. She abruptly developed fulminant hepatitis and disseminated intravascular coagulation, and died 3 days later. VZV DNA and antigens were detected in the peripheral blood (6 x 10(8) copies/mL) and a postmortem liver specimen, respectively. The exposure to VZV was not confirmed and no skin lesions were observed. VZV infection should be considered in patients with unexplained liver dysfunction under severe immunosuppressive condition, even in the absence of viral exposure and skin involvement.