Haploinsufficiency of NKX2-1 is likely to contribute to developmental delay involving 14q13 microdeletions.

Nucleotide variations or deletions in the NK2 homeobox 1 gene (NKX2-1), located at 14q13.3, lead to symptoms associated with the brain, lungs, and thyroid, and the combination of these phenotypes is clinically recognized as the brain-lung-thyroid syndrome. Many types of nucleotide variants of NKX2-1 have been identified, and phenotypic variability has been reported. Chromosomal deletions involving NKX2-1 have also been reported; however, phenotypic differences between patients with nucleotide variants of NKX2-1 and patients with chromosomal deletions involving NKX2-1 have not been well established. Recently, we identified seven patients with 14q13 microdeletions involving the NKX2-1. Most patients exhibited developmental delay. This inquiry arises regarding the potential existence of haploinsufficiency effects beyond those attributed to NKX2-1 within the 14q13 microdeletion. However, a literature review has shown that developmental delay is not rare in patients with nucleotide alterations in NKX2-1. Rather, motor function impairment may have affected the total developmental assessment, and the haploinsufficiency of genes contiguous to NKX2-1 is unlikely to contribute to developmental delay.

Serum cytokine profile in pediatric Sweet's syndrome: a case report.

BACKGROUND: Sweet's syndrome is characterized by fever, leukocytosis, and tender erythematous papules or nodules. It is a rare condition, particularly in the pediatric population, and has recently been proposed to be an autoinflammatory disease that occurs due to innate immune system dysfunction, involving several cytokines, which causes abnormally increased inflammation. To the best of our knowledge, no report has documented the cytokine profile in a pediatric patient with Sweet's syndrome. CASE PRESENTATION: A previously healthy 34-month-old Japanese girl was hospitalized because of remittent fever and pain in her right lower extremity with erythematous nodules. A skin biopsy of the eruption revealed dermal perivascular neutrophilic infiltration with no evidence of vasculitis, which led to the diagnosis of Sweet's syndrome. She was prescribed with orally administered prednisolone and a prompt response was observed; then, the prednisolone dose was tapered. During treatment she developed upper and lower urinary tract infections, after which her cutaneous symptoms failed to improve despite increasing the prednisolone dosage. To avoid long-term use of systemic corticosteroids, orally administered potassium iodide was initiated, but it was unsuccessful. However, orally administered colchicine along with prednisolone effectively ameliorated her symptoms, and prednisolone dosage was reduced again. We analyzed the circulating levels of interleukin-1ß, interleukin-6, interleukin-18, neopterin, and soluble tumor necrosis factor receptors I and II, in order to clarify the pathogenesis of Sweet's syndrome. Of these cytokines, only interleukin-6 levels were elevated prior to orally administered prednisolone therapy. Following therapy, the elevated interleukin-6 levels gradually diminished to almost normal levels; interleukin-1ß and interleukin-18 stayed within normal ranges throughout the treatment. Neopterin became marginally elevated after the start of treatment. Both soluble tumor necrosis factor receptor I and soluble tumor necrosis factor receptor II levels increased shortly after the onset of urinary tract infections. CONCLUSIONS: This is the first case report of pediatric Sweet's syndrome in which serum cytokine levels were investigated. Future studies should gather more evidence to elucidate the pathophysiology of Sweet's syndrome.

A Case of Apparent Life-Threatening Event: Comorbid Gastric Volvulus Associated Gastroesophageal Reflux Disease and Epilepsy in a 4-Month-Old Boy.

Most isolated episodes of apparent life-threatening events (ALTEs) do not lead to the diagnosis of serious conditions, and their prognoses are generally benign. However, recurrent ALTEs are often associated with a risk of future serious adverse events and should be evaluated for appropriate management. Here we present ALTE case in which gastric volvulus associated gastroesophageal reflux disease was detected as an etiology initially, followed by the detection of epilepsy as another etiology. Clinicians should consider possibility of two or more etiologies in a single recurrent ALTE case.

Human parechovirus infections and child myositis cases associated with genotype 3 in Osaka City, Japan, 2014.

Human parechovirus (HPeV) infects humans early in life and typically causes asymptomatic or mild diseases such as gastrointestinal and respiratory illness but sometimes leads to more serious consequences in neonates and young infants. In 2014, we detected HPeV from 38 patients by real-time reverse transcription-PCR in Osaka City, Japan, and 33 HPeV strains were genotyped based on their VP1 sequences. HPeV genotype 3 (HPeV-3) was the most prevalent and accounted for 22 cases (66.7%) followed by nine HPeV-1 (27.3%), one HPeV-2 (3.0%) and one HPeV-4 (3.0%). Phylogenetic analysis revealed that detected HPeV-3 strains were divided into three genetically distinct groups. One was characterized by a novel single amino acid deletion mutation at the N terminus of the 2A protein as well as the VP1 sequence, whereas the others were closely related to HPeV-3 strains detected in Japan in either 2008 or 2011. These HPeV-3 groups were detected from patients with various symptoms including three myositis cases. Recent papers have demonstrated that HPeV-3 was the aetiological agent for epidemic myalgia exclusively among adults from Yamagata Prefecture in Japan. Here, we provide clinical details and episodes of three myositis patients including an adult and two children in Osaka City, Japan. Our results suggest that HPeV-3 is a causative agent of myositis not only in adults but also in children.