The presence of diminished white matter and corpus callosal thinning in a case with a SOX9 mutation

SOX9 is responsible for campomelic dysplasia (CMPD). Symptoms of CMPD include recurrent apnea, upper respiratory infection, facial features, and shortening of the lower extremities. The variant acampomelic CMPD (ACMPD) lacks long bone curvature. A patient showed macrocephaly (+3.9 standard deviations [SD]) and minor anomalies, such as hypertelorism, palpebronasal fold, small mandible, and a cleft of soft palate without long bone curvature. From three months of age, he required tracheal intubation and artificial respiration under sedation because of tracheomalacia. Cranial magnetic resonance imaging was normal at one month of age but showed ventriculomegaly, hydrocephaly, and the corpus callosum thinning at two years of age. Exome sequencing revealed a de novo novel mutation, c. 236A > C, p (Q79P), in SOX9. Sox9 is thought to be crucial in neural stem cell development in the central and peripheral nervous system along with Sox8 and Sox10 in mice. In humans, neuronal abnormalities have been reported in cases of CMPD and ACMPD, including relative macrocephaly in 11 out of 22 and mild lateral ventriculomegaly in 2 out of 22 patients. We encountered a two-year old boy with ACMPD presenting with tracheomalacia and macrocephaly with a SOX9 mutation. We described for the first time an ACMPD patient with acquired diminished white matter and corpus callosal thinning, indicating the failure of oligodendrocyte/astrocyte development postnatally. This phenotype suggests that SOX9 plays a crucial role in human central nervous system development. Further cases are needed to clarify the relationship between human neural development and SOX9 mutations.     

A patient with early myoclonic encephalopathy (EME) with a de novo KCNQ2 mutation

Background

The potassium voltage-gated channel subfamily Q member 2 (KCNQ2) gene has been reported to be associated with various types of epilepsy, including benign familial neonatal seizure (BFNS), early infantile epileptic encephalopathy (EIEE), and unclassified early onset encephalopathies. We herein report a patient with early myoclonic encephalopathy (EME) caused by a KCNQ2 mutation.

A de novo deletion of 20q11.2-q12 in a boy presenting with abnormal hands and feet, retinal dysplasia, and intractable feeding difficulty

Proximal interstitial deletions involving 20q11-q12 are very rare. Only two cases have been reported. We describe another patient with 20q11.21-q12 deletion. We precisely mapped the 6.5-Mb deletion and successfully determined the deletion landmarks at the nucleotide level. Common clinical features among the three cases include developmental delay, intractable feeding difficulties with gastroesophageal reflux, and facial dysmorphism including triangular face, hypertelorism, and hypoplastic alae nasi, indicating that the 20q11.2-q12 deletion can be a clinically recognizable syndrome. This is also supported by the fact that the three deletions overlap significantly. In addition, unique features such as arthrogryposis/fetal akinesia (hypokinesia) deformation and retinal dysplasia are recognized in the patient reported herein.     

Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides

The mammalian natriuretic peptide family consists of atrial (ANP), brain [B-type; BNP] and C-type natriuretic peptide (CNP) and three receptors, natriuretic receptors-A (NPR-A), -B (NPR-B) and -C (NPR-C). Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively. By contrast, CNP is mainly expressed in the central nervous system, bone and vasculature. Plasma concentrations of both ANP and BNP are elevated in patients with cardiovascular disease, though the magnitude of the increase in BNP is usually greater than the increase in ANP. This makes BNP is a clinically useful diagnostic marker for several pathophysiological conditions, including heart failure, ventricular remodeling and pulmonary hypertension, among others. Recent studies have shown that in addition to BNP-32, proBNP-108 also circulates in human plasma and that levels of both forms are increased in heart failure. Furthermore, proBNP-108 is O-glycosylated and circulates at higher levels in patients with severe heart failure. In this review we discuss recent progress in our understanding of the biochemistry, molecular biology and clinical relevance of the natriuretic peptide system.     

A case of Baraitser–Winter syndrome with unusual brain MRI findings: Pachygyria,subcortical-band heterotopia,and periventricular heterotopia

Baraitser–Winter syndrome (BaWS) is characterized by iris coloboma, ptosis, hypertelorism, and mental retardation; it is a rare multiple congenital anomaly or a mental-retardation syndrome of unknown etiology. Patients suffering from this syndrome have been also found to show brain anomalies such as pachygyria, subcortical-band heterotopia (SBH), and hippocampal malformations; therefore, these anomalies have been included in the phenotypic spectrum of this syndrome. We report the case of a Japanese boy suffering from BaWS; the patient’s brain magnetic resonance imaging scan revealed pachygyria, SBH, and periventricular heterotopia. However, the results of the genome-wide array comparative genomic hybridization did not reveal any chromosomal rearrangements.     

A novel methodology to evaluate health impacts caused by VOC exposures using real-time VOC and Holter monitors

While various volatile organic compounds (VOCs) are known to show neurotoxic effects, the detailed mechanisms of the action of VOCs on the autonomic nervous system are not fully understood, partially because objective and quantitative measures to indicate neural abnormalities are still under development. Nevertheless, heart rate variability (HRV) has been recently proposed as an indicative measure of the autonomic effects. In this study, we used HRV as an indicative measure of the autonomic effects to relate their values to the personal concentrations of VOCs measured by a real-time VOC monitor. The measurements were conducted for 24 hours on seven healthy subjects under usual daily life conditions. The results showed HF powers were significantly decreased for six subjects when the changes of total volatile organic compound (TVOC) concentrations were large, indicating a suppression of parasympathetic nervous activity induced by the exposure to VOCs. The present study indicated these real-time monitoring was useful to characterize the trends of VOC exposures and their effects on autonomic nervous system.     

Neuroradiologic findings in Sotos syndrome

Sotos syndrome is a well-known anomaly syndrome characterized by overgrowth, characteristic facial gestalt, and developmental delay, and haploinsufficiency of the NSD1 gene has been revealed as one of the major genetic causes. However, there have been only a few reports on neuroradiologic findings by computed tomography (CT) or magnetic resonance imaging (MRI), and functional examination of the brain has not been reported. We examined three cases with typical Sotos syndrome, which also were confirmed by genetic analysis with a specific probe for the NSD1 gene. The results of MRI showed the characteristic features that have been reported previously. The findings obtained by using single-photon emission computed tomography and magnetic resonance spectroscopy suggested an association between mental delay and behavioral tendency in Sotos syndrome and immaturity in frontal brain function.     

Indication of femorotibial and femoroperoneal bypass for Buerger's disease

Infrapopliteal bypass with autogenous vein graft was performed in twenty-three patients of thromboangiitis obliterans (Buerger's Disease) during the past 8 years. The outflow vessel of the graft had the direct connection with the pedal arch in 3 cases. In 20 cases the graft was anastomosed to the solitary tibial or peroneal segment, in which the occlusive lesion existed between the outflow vessel and pedal arch, or otherwise, the pedal arch was not opacified in the arteriogram. The length of the solitary tibial or peroneal segment of the successful cases ranged from 11.5 cm to 29.0 cm. The cumulative patency rates of the 23 bypass grafts at 3 months, 1 year, 3 years and 5 years were 86.7%, 77.3%, 77.3%, 77.3% respectively. This result is comparable to those of other authors. When the solitary tibial or peroneal artery is found out and is longer than 12 cm in the arteriogram of Buerger's Disease, we are going to perform bypass surgery to the vessel. If the foot is already necrotic, the amputation should be carried out several days or several weeks after the successful reconstructive surgery.