Pathogenic 12-kb copy-neutral inversion in syndromic intellectual disability identified by high-fidelity long-read sequencing.

We report monozygotic twin girls with syndromic intellectual disability who underwent exome sequencing but with negative pathogenic variants. To search for variants that are unrecognized by exome sequencing, high-fidelity long-read genome sequencing (HiFi LR-GS) was applied. A 12-kb copy-neutral inversion was precisely identified by HiFi LR-GS after trio-based variant filtering. This inversion directly disrupted two genes, CPNE9 and BRPF1, the latter of which attracted our attention because pathogenic BRPF1 variants have been identified in autosomal dominant intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP), which later turned out to be clinically found in the twins. Trio-based HiFi LR-GS together with haplotype phasing revealed that the 12-kb inversion occurred de novo on the maternally transmitted chromosome. This study clearly indicates that submicroscopic copy-neutral inversions are important but often uncharacterized culprits in monogenic disorders and that long-read sequencing is highly advantageous for detecting such inversions involved in genetic diseases.

Multicenter clinical trial on sentinel lymph node biopsy using superparamagnetic iron oxide nanoparticles and a novel handheld magnetic probe.

BACKGROUND: Sentinel lymph node biopsy is a standard staging procedure for early axillary lymph node-negative breast cancer. As an alternative to the currently used radioactive tracers for sentinel lymph node (SLN) detection during the surgical procedure, a number of studies have shown promising results using superparamagnetic iron oxide (SPIO) nanoparticles. Here, we developed a new handheld, cordless, and lightweight magnetic probe for SPIO detection. METHODS: Resovist (SPIO nanoparticles) were detected by the newly developed handheld probe, and the SLN detection rate was compared to that of the standard radioisotope (RI) method using radioactive colloids (99m Tc) and a blue dye (indigo carmine). This was a multicenter prospective clinical trial that included 220 patients with breast cancer scheduled for sentinel node biopsy after a clinical diagnosis of negative axillary lymph node from three facilities in Japan. RESULTS: Of the 210 patients analyzed, SLN was detected in 94.8% (199/210 cases, 90% confidence interval [CI]) with our magnetic method and in 98.1% (206/210 cases, 90% CI) with the RI method. The magnetic method exceeded the threshold identification rate of 90%. CONCLUSION: This was the first clinical study to use a novel handheld magnetometer to detect SLN, which we demonstrate to be not inferior to the RI method.

De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy.

V-type proton (H+) ATPase (v-ATPase) is a multi-subunit proton pump that regulates pH homeostasis in all eukaryotic cells; in neurons, v-ATPase plays additional and unique roles in synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.Asp100Tyr, p.Asp349Asn, p.Asp371Gly) in ATP6V1A, encoding the A subunit of v-ATPase, in four patients with developmental encephalopathy with epilepsy. Early manifestations, observed in all patients, were developmental delay and febrile seizures, evolving to encephalopathy with profound delay, hypotonic/dyskinetic quadriparesis and intractable multiple seizure types in two patients (p.Pro27Arg, p.Asp100Tyr), and to moderate delay with milder epilepsy in the other two (p.Asp349Asn, p.Asp371Gly). Modelling performed on the available prokaryotic and eukaryotic structures of v-ATPase predicted p.Pro27Arg to perturb subunit interaction, p.Asp100Tyr to cause steric hindrance and destabilize protein folding, p.Asp349Asn to affect the catalytic function and p.Asp371Gly to impair the rotation process, necessary for proton transport. We addressed the impact of p.Asp349Asn and p.Asp100Tyr mutations on ATP6V1A expression and function by analysing ATP6V1A-overexpressing HEK293T cells and patients' lymphoblasts. The p.Asp100Tyr mutant was characterized by reduced expression due to increased degradation. Conversely, no decrease in expression and clearance was observed for p.Asp349Asn. In HEK293T cells overexpressing either pathogenic or control variants, p.Asp349Asn significantly increased LysoTracker® fluorescence with no effects on EEA1 and LAMP1 expression. Conversely, p.Asp100Tyr decreased both LysoTracker® fluorescence and LAMP1 levels, leaving EEA1 expression unaffected. Both mutations decreased v-ATPase recruitment to autophagosomes, with no major impact on autophagy. Experiments performed on patients' lymphoblasts using the LysoSensor™ probe revealed lower pH of endocytic organelles for p.Asp349Asn and a reduced expression of LAMP1 with no effect on the pH for p.Asp100Tyr. These data demonstrate gain of function for p.Asp349Asn characterized by an increased proton pumping in intracellular organelles, and loss of function for p.Asp100Tyr with decreased expression of ATP6V1A and reduced levels of lysosomal markers. We expressed p.Asp349Asn and p.Asp100Tyr in rat hippocampal neurons and confirmed significant and opposite effects in lysosomal labelling. However, both mutations caused a similar defect in neurite elongation accompanied by loss of excitatory inputs, revealing that altered lysosomal homeostasis markedly affects neurite development and synaptic connectivity. This study provides evidence that de novo heterozygous ATP6V1A mutations cause a developmental encephalopathy with a pathomechanism that involves perturbations of lysosomal homeostasis and neuronal connectivity, uncovering a novel role for v-ATPase in neuronal development.

KIF1A mutation in a patient with progressive neurodegeneration.

Kinesins are a large superfamily of molecular motors. They move along microtubule filaments and are powered by the hydrolysis of ATP. This transport system is essential for neuronal function and survival. KIF1A belongs to the kinesin 3 family and involves in the anterograde transport of synaptic vesicle precursors along axons. Several studies confirmed that KIF1A mutations cause spastic paraplegia and sensory neuropathy in an autosomal-recessive fashion. A missense mutation in the KIF1A gene (p.Thr99Met) has been reported in a patient with intellectual disability (ID), axial hypotonia and peripheral spasticity. Mild atrophy of the cerebellar vermis was found on magnetic resonance imaging. The mutation was heterozygous and de novo. We identified the second patient with the p.T99M mutation in the KIF1A gene by whole-exome sequencing. He showed severe ID, spasticity, optic atrophy, neurogenic bladder, growth failure and progressive cerebellar atrophy. The p.T99M mutation may be a common recurrent mutation. We suppose that this specific mutation of KIF1A shows a novel neurodegenerative syndrome.

[Successful treatment with intravenous steroid pulse therapy of a boy with recurrent idiopathic sixth nerve palsy].

A 3-year-old boy developed left-sided convergent strabismus one week after upper respiratory infection. All examinations, including analysis of cerebrospinal fluid, a tensilon test, and brain MRI, were negative. He was diagnosed with idiopathic sixth nerve palsy. His symptom resolved gradually with vitamin B12, and remitted completely three months after onset. At the age of 6 years, he experienced recurrence of left-sided sixth nerve palsy. After vitamin B12 failed, his symptom responded markedly to intravenous steroid pulse therapy starting on day 26 after relapse. He has been symptom-free for three years since the second remission. Steroid therapy might be effective, and should be considered in children with idiopathic sixth nerve palsy who do not show spontaneous remission.

[Evaluation of six cases with hypothalamic hamartoma: the relationship between MRI findings and clinical features].

OBJECTIVE: We evaluated the relationship between MRI findings and clinical features in patients with hypothalamic hamartoma (HH). METHODS: We retrospectively reviewed MRI and clinical data (mental retardation, precocious puberty, behavioral problems, and epilepsy) in six patients (3 males and 3 females, ages 12 to 26) with HH. Based on the MRI classification by Arita, HH was classified into two types: parahypothalamic (P) and intrahypothalamic (I). RESULTS: Only one patient was classified as having P-type HH and five were classified as having I-type HH. The patient with P-type HH (diameter 21 mm) showed precocious puberty and mild behavioral problems, but did not developed epilepsy. On the other hand, all patients with I-type HH (diameter 10-32 mm, median 17 mm) developed epilepsy and behavioral problems. Except for one patient, who had the smallest sized HH, I-type four patients developed mental retardation and precocious puberty. Among patients with I-type HH, the size of the tumor was inversely correlated with the age at epilepsy onset and with the degree of mental retardation (DQ/IQ). CONCLUSION: Our data suggested that the MRI classification by Arita, when combined with tumor size, might be helpful in predicting the clinical manifestations in patients with HH.

Detection of breast cancer with a computer-aided detection applied to full-field digital mammography.

A study was conducted to evaluate the sensitivity of computer-aided detection (CAD) with full-field digital mammography in detection of breast cancer, based on mammographic appearance and histopathology. Retrospectively, CAD sensitivity was assessed in total group of 152 cases for subgroups based on breast density, mammographic presentation, lesion size, and results of histopathological examination. The overall sensitivity of CAD was 91 % (139 of 152 cases). CAD detected 100 % (47/47) of cancers manifested as microcalcifications; 98 % (62/63) of those manifested as non-calcified masses; 100 % (15/15) of those manifested as mixed masses and microcalcifications; 75 % (12/16) of those manifested as architectural distortions, and 69 % (18/26) of those manifested as focal asymmetry. CAD sensitivity was 83 % (10/12) for cancers measuring 1-10 mm, 92 % (37/40) for those measuring 11-20 mm, and 92 % (92/100) for those measuring >20 mm. There was no significant difference in CAD detection efficiency between cancers in dense breasts (88 %; 69/78) and those in non-dense breasts (95 %; 70/74). CAD showed a high sensitivity of 91 % (139/152) for the mammographic appearance of cancer and 100 % sensitivity for identifying cancers manifested as microcalcifications. Sensitivity was not influenced by breast density or lesion size. CAD should be effective for helping radiologists detect breast cancer at an earlier stage.

A Case of Paraneoplastic Neurological Syndrome Associated with Breast Cancer Detected while Searching for the Cause of Involuntary Movement.

Our case involved a 66-year-old woman who noticed progressive asymmetric involuntary movement, difficulty speaking, and difficulty swallowing. The patient fractured her femur due to a lower extremity involuntary movement while walking. During the course of her treatment for the fracture, her neurological symptoms worsened. Approximately 2 months after becoming aware of her symptoms, she visited our clinic for evaluation of difficulty with unassisted walking and weight loss due to dysphagia. To identify the cause of her neurological symptoms, hematological examination, brain magnetic resonance imaging, single-photon emission computed tomography for cerebral blood flow, electroencephalography, and a somatosensory evoked potential test were conducted. Although the cause of her neurological symptoms could not be determined, computed tomography revealed the presence of breast cancer, which led us to suspect paraneoplastic neurological syndrome (PNS). After breast cancer treatment, her neurological symptoms improved simultaneously. Therefore, the patient was retrospectively diagnosed with PNS. We report a case of PNS whose neurological symptoms followed a subacute course and were relieved after breast cancer treatment.

Newborn screening for spinal muscular atrophy in Osaka -challenges in a Japanese pilot study.

OBJECTIVE: This study aimed to establish an optional newborn screening program for spinal muscular atrophy (SMA-NBS) in Osaka. METHODS: A multiplex TaqMan real-time quantitative polymerase chain reaction assay was used to screen for SMA. Dried blood spot samples obtained for the optional NBS program for severe combined immunodeficiency, which covers about 50% of the newborns in Osaka, were used. To obtain informed consent, participating obstetricians provided information about the optional NBS program to all parents by giving leaflets to prospective parents and uploading the information onto the internet. We prepared a workflow so that babies that were diagnosed with SMA through the NBS could be treated immediately. RESULTS: From 1 February 2021 to 30 September 2021, 22,951 newborns were screened for SMA. All of them tested negative for survival motor neuron (SMN)1 deletion, and there were no false-positives. Based on these results, an SMA-NBS program was established in Osaka and included in the optional NBS programs run in Osaka from 1 October 2021. A positive baby was found by screening, diagnosed with SMA (the baby possessed 3 copies of the SMN2 gene and was pre-symptomatic), and treated immediately. CONCLUSION: The workflow of the Osaka SMA-NBS program was confirmed to be useful for babies with SMA.

Association between cerebrospinal fluid parameters and developmental and neurological status in glucose transporter 1 deficiency syndrome.

OBJECTIVE: In glucose transporter 1 deficiency syndrome (Glut1DS), cerebrospinal fluid glucose (CSFG) and CSFG to blood glucose ratio (CBGR) show significant differences among groups classified by phenotype or genotype. The purpose of this study was to investigate the association between these biochemical parameters and Glut1DS severity. METHODS: The medical records of 45 patients who visited Osaka University Hospital between March 2004 and December 2021 were retrospectively examined. Neurological status was determined using the developmental quotient (DQ), assessed using the Kyoto Scale of Psychological Development 2001, and the Scale for the Assessment and Rating of Ataxia (SARA). CSF parameters included CSFG, CBGR, and CSF lactate (CSFL). RESULTS: CSF was collected from 41 patients, and DQ and SARA were assessed in 24 and 27 patients, respectively. Simple regression analysis showed moderate associations between neurological status and biochemical parameters. CSFG resulted in a higher R2 than CBGR in these analyses. CSF parameters acquired during the first year of life were not comparable to those acquired later. CSFL was measured in 16 patients (DQ and SARA in 11 and 14 patients, respectively). Although simple regression analysis also showed moderate associations between neurological status and CSFG and CSFL, the multiple regression analysis for DQ and SARA resulted in strong associations through the use of a combination of CSFG and CSFL as explanatory variables. CONCLUSION: The severity of Glut1DS can be predicted from CSF parameters. Glucose and lactate are independent contributors to the developmental and neurological status in Glut1DS.

FDG-PET/CT in the diagnosis of recurrent breast cancer.

BACKGROUND: An advantage of PET/CT has been demonstrated for diagnosis of several tumor entities. In patients with breast cancer, early diagnosis and accurate restaging of recurrence after surgery is important for selection of the most appropriate therapeutic strategy. Purpose To evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG), for follow-up of patients with suspected recurrent breast cancer. MATERIAL AND METHODS: Forty-seven patients with suspected recurrent breast cancer underwent PET/CT. The PET and PET/CT images were interpreted without knowledge of the results of other diagnostic modalities, and compared with each other with reference to the final diagnosis. RESULTS: Twenty-five (53%) patients suffered tumor recurrence. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 96%, 91%, 92%, 95%, and 94%, respectively. In comparison with PET, PET/CT had a higher sensitivity and accuracy (96% vs. 80% and 94% vs. 81%, respectively). The difference in diagnostic accuracy between PET/CT and PET was significant (P < 0.05). CONCLUSION: The present findings indicate that PET/CT is an accurate, sensitive and reliable modality for screening and detection of breast cancer recurrence. PET/CT appears to be an effective surveillance tool, as it is able to cover the whole body in a single procedure and shows good performance.

Use of Liquid Biopsy to Detect PIK3CA Mutation in Metastatic Breast Cancer.

BACKGROUND: PIK3CA is associated with tumor progression, and the prevalence of PIK3CA mutation is high in breast cancer. Liquid biopsy offers convenient, noninvasive, and real-time insight into genetic alteration. In this study, we used liquid biopsy to detect PIK3CA mutations in patients with breast cancer. METHODS: We recruited patients with histologically confirmed breast cancer and distant metastases between April 2020 and September 2020. Circulating DNA was extracted from plasma (ctDNA) and exosomes (exoDNA). PIK3CA mutations (exons 9 and 20) were analyzed by droplet digital PCR. RESULTS: Of the 52 patients recruited, 16 had PIK3CA mutations in tumor tissue or blood: 9 had exon 9 mutations (E542K and E545K) and 8 had exon 20 mutations (H1047 L and H1047R). In 8 (15%) of the 52 patients, PIK3CA mutations were detected by liquid biopsies using ctDNA in 5 (9%), exoDNA in 6 (11%), and both ctDNA and exoDNA in 3 (6%). Of the 8 patients with PIK3CA mutations detected by liquid biopsies, 3 had no PIK3CA mutations in the primary tumors. CONCLUSIONS: PIK3CA mutations can be detected by liquid biopsy even in patients with no PIK3CA mutations in their primary tumors; thus, combination analysis using tissue and liquid biopsies can provide clinically useful information for patients with breast cancer.

SLC2A1 gene analysis of Japanese patients with glucose transporter 1 deficiency syndrome.

Glucose transporter 1 deficiency syndrome (Glut1-DS) is a congenital metabolic disorder characterized by refractory seizures with early infantile onset, developmental delay, movement disorders and acquired microcephaly. Glut1-DS is caused by heterozygous abnormalities of the SLC2A1 (Glut1) gene, whose product acts to transport glucose into the brain across the blood-brain barrier. We analyzed the SLC2A1 gene in 12 Japanese Glut1-DS patients who were diagnosed by characteristic clinical symptoms and hypoglycorrhachia as follows: all patients had infantile-onset seizures and mild to severe developmental delay, and ataxia was detected in 11 patients. For the 12 patients, we identified seven different mutations (three missense, one nonsense, two frameshift and one splice-site) in exons and exon-intron boundaries of the SLC2A1 gene by direct sequencing, of which six were novel mutations. Of the remaining five patients who had no point mutations and underwent investigation by multiplex ligation-dependent probe amplification, a complex abnormality with deletion and duplication was identified in one patient: this is the first case of such recombination of the SLC2A1 gene. Changes in regulatory sequences in the promoter region or genes other than SLC2A1 might be responsible for onset of Glut1-DS in the other four patients (33%) without SLC2A1 mutation.

[Successful treatment with additional plasmapheresis for the exacerbation of acute neurological symptoms in a girl with multiple sclerosis].

Few studies have indicated the efficacy of plasmapheresis in children with multiple sclerosis (MS). We report a 10-year-old girl with MS who was successfully treated with plasmapheresis. She experienced the first episode (vomiting and unconsciousness) at the age of eight years. After two years and six months remission period, she had a relapse with left hemiplegia. Her symptoms did not respond to high-dose intravenous methylprednisolone or immunoglobulin therapies, and rapidly deteriorated. After bulbar palsy was observed, plasmapheresis (total : every two days, seven times) was initiated at the 17th day during the relapse. Neurological symptoms improved remarkably after the second trial of plasmapheresis. There were no complications associated with plasmapheresis. Plasmapheresis may be effective as an additional therapy for exacerbation of acute neurological symptoms in children with MS.

[Changes of brain edema after initiation of mild hypothermia therapy in children].

To determine the effects of mild hypothermia therapy (34 degrees C) for brain edema caused by hypoxic ischemic encephalopathy (HIE) or acute encephalitis/encephalopathy, we reviewed the charts and serial brain CT images in six children (males 3, average age 1.6 years) treated with mild hypothermia therapy between November 2006 and April 2009. Both of the two children with HIE after cardiopulmonary arrest did not show any deterioration of brain edema after the initiation of hypothermia therapy. However, two of four non-HIE patients (acute encephalitis/encephalopathy 3 cases and metabolic encephalopathy plus HIE 1 case) showed progressive brain edema during the cooling phase and re-warming phase, respectively. There were no differences between patients with and those without progressive brain edema with regard to the interval until initiation of mild hypothermia therapy, duration of cooling phase, duration of re-warming phase, or peak serum NSE (neuron-specific enolase) levels. However, two children with progressive brain edema showed a delayed NSE peak time (15 and 13 days after onset, respectively), compared with those without progressive brain edema (2-6 days after onset). Our study suggests that serial measurement of serum NSE might be useful marker for adjusting the methods of hypothermia therapy according to neuropathology. Further study is necessary to establish optimal hypothermia therapy especially in children with acute encephalitis/ encephalopathy.

Epilepsy in patients with advanced Fukuyama congenital muscular dystrophy.

BACKGROUND: Recent advances in respiratory management have improved survival for patients with Fukuyama congenital muscular dystrophy (FCMD), characterized by congenital muscular dystrophy and brain malformation. Previous studies reported that more than half of patients exhibit seizures in childhood. However, little is known about epilepsy after childhood. METHODS: To elucidate the long-term clinical course of epilepsy, we retrospectively reviewed all medical records in nine patients (6 males, mean age 20.7 years) with FCMD diagnosed between 1981 and 2019. RESULTS: The follow-up periods ranged from 6 to 30 years (mean 18.4 years). A total of 75 EEG recordings were available from nine patients. In some patients, EEGs were normal during early childhood but tended to show paroxysmal discharges with age. Overall, epileptic seizures were observed in six patients. Except for one presenting with afebrile seizure at one year of age, the remaining five patients developed epilepsy between 13 and 22 years of age. The most common seizure type was focal impaired awareness seizure. After adolescence, four patients exhibited status epilepticus. Their convulsive movements of the seizures became less prominent with progression of the disease. At the last evaluation, most patients (5/6) had uncontrolled seizures. CONCLUSIONS: Despite presence of distinct brain malformation, epileptic seizures may develop after childhood in FCMD patients. Our experience suggests that clinicians should be careful not to overlook epileptic seizures, especially in advanced-stage patients who had profound muscle weakness.

Neoadjuvant Endocrine Therapy for Operable Breast Cancer: A Retrospective Analysis of Real-World Use.

BACKGROUND: A retrospective study of the real-world use of neoadjuvant endocrine therapy (NET) is important for standardizing the role of NET in breast cancer care. METHODS: In a consecutive series of women with operable breast cancer who received NET for ≥28 days, associations of NET objectives, NET outcomes, adjuvant chemotherapy use after NET, and survival with clinicopathological factors were examined. RESULTS: NET objectives were reduction in surgical extent in 49 patients, avoidance of surgery in 31, and treatment until scheduled surgery in 8. The mean duration of NET was 349.5 (range, 34-1,923), 869.8 (range, 36-4,859), and 55.8 (range, 39-113) days, respectively, in these cohorts (success rate: 79.6%, 64.5%, and 100%, respectively), and the differences were significant. Among patients in the former two cohorts, progression-free survival was significantly better in patients with stage 0 or I disease, ductal carcinoma in situ or invasive ductal carcinoma, ≥71% estrogen receptor (ER) positivity, and the surgical extent reduction cohort than the other counterparts. Postoperative chemotherapy use was significantly associated with lymph node metastasis, a high Ki67 labeling index, lymphovascular invasion, and a high preoperative endocrine prognostic index at the time of surgery after NET. Better recurrence-free survival after surgery was significantly associated with high ER expression after NET or high progesterone receptor expression before or after NET. CONCLUSIONS: NET can help reduce surgical extent or avoid surgery in women with early breast cancer, ductal carcinoma, or high ER expression. NET may also aid in decisions related to postoperative systemic therapy to improve survival.

Magnetically Guided Localization Using a Guiding-Marker System® and a Handheld Magnetic Probe for Nonpalpable Breast Lesions: A Multicenter Feasibility Study in Japan.

Accurate pre-operative localization of nonpalpable lesions plays a pivotal role in guiding breast-conserving surgery (BCS). In this multicenter feasibility study, nonpalpable breast lesions were localized using a handheld magnetic probe (TAKUMI) and a magnetic marker (Guiding-Marker System®). The magnetic marker was preoperatively placed within the target lesion under ultrasound or stereo-guidance. Additionally, a dye was injected subcutaneously to indicate the extent of the tumor excision. Surgeons checked for the marker within the lesion using a magnetic probe. The magnetic probe could detect the guiding marker and accurately localize the target lesion intraoperatively. All patients with breast cancer underwent wide excision with a safety margin of ≥5 mm. The presence of the guiding-marker within the resected specimen was the primary outcome and the pathological margin status and re-excision rate were the secondary outcomes. Eighty-seven patients with nonpalpable lesions who underwent BCS, from January to March of 2019 and from January to July of 2020, were recruited. The magnetic marker was detected in all resected specimens. The surgical margin was positive only in 5/82 (6.1%) patients; these patients underwent re-excision. This feasibility study demonstrated that the magnetic guiding localization system is useful for the detection and excision of nonpalpable breast lesions.

Birth length is a predictor of adiponectin levels in Japanese young children.

BACKGROUND: Adiponectin has been shown to be inversely related to birth weight in schoolchildren and adolescents. However, the available information regarding a relation between birth size and adiponectin in infants and preschoolers is limited. METHODS: A longitudinal study was conducted among healthy Japanese children, and serum adiponectin levels were measured at consecutive visits. The effect of sex, gestational age, birth length, birth weight, or placental weight on adiponectin was analyzed by using a linear mixed model for repeated measures. RESULTS: Eighty-three children were evaluated. The age range at the first visit was 0.07-5.3 years. A total number of 227 measurements were made, 1-12 per subject (median, 3) and the duration of follow-up ranged from 1 day to 2.3 years (median, 1.0 years). The subjects were divided into four groups according to the age at the first visit: (1) 0-2 months (n = 29), (2) 3 months to 1 year (n = 17), (3) 2-3 years (n = 19) and (4) 4-5 years (n = 18). In the multivariate model, birth length (coefficient = 3.94, 95% CI, 0.23-7.65) was an independent predictor of serum adiponectin levels in subjects aged 0-2 months. Gestational age (3.53, 1.14-5.92), birth length (-2.71, -4.90 to -0.53) and placental weight (2.58, 0.86-4.29) were independent predictors of serum adiponectin levels in subjects aged 4-5 years. CONCLUSION: Birth length, not birth weight, is an independent predictor of serum adiponectin levels in Japanese young children.

Epilepsy in patients with congenital cytomegalovirus infection.

Patients with congenital cytomegalovirus (CMV) infection were at high risk for postnatal seizures, but little is known about epilepsy associated with congenital CMV infection. To define the features of epilepsy, we retrospectively reviewed the clinical, laboratory and neuroradiographic findings in 19 children (male 9) with congenital CMV infection. Seven (37%) patients had developed epilepsy (partial seizure 5 and epileptic spasms 2) at a mean age of 20 months (range 2-37 months). During the clinical course, West syndrome occurred in only three patients. The most common seizure type in our series was partial seizure. At the time of last follow-up (mean 96 months), seizures remained uncontrolled in six patients. Neonatal clinical manifestations (gestational age, gender distribution, birth asphyxia or symptoms at birth) were not predictive of the development of epilepsy. On the contrary, some neuroradiographic findings (ventricular dilatation and migration disorder) were significantly associated with the development of epilepsy.