CTEV WITH MEGA URINARY BLADDER: A CASE REPORT

Congenital talipes equino varus (CTEV), also known as congenital club foot is one of the common developmental deformities occurring at ankle, subtalar and metatarsal joints. Three elements comprise this deformity- equinus, inversion of foot and adduction of the forefoot relative to the hind-foot and equinus. The incidence of the deformity is 1 per 1000 live births. 20% of cases are associated with distal arthrogryposis, congenital myotonic dystrophy, myelomeningocele, amniotic band sequence and genetic syndromes such as trisomy 18 or chromosome 22q11 deletion syndrome, in the remaining cases the deformity is isolated and the exact etiology is unknown. We are presenting a case of aborted male fetus of 20 weeks with congenital talipes equino varus in left foot with enlarged urinary bladder. The purpose of this report is to document the association of CTEV with enlarged urinary bladder.

Taiwanese Clinical Experience with Noninvasive Prenatal Testing for DiGeorge Syndrome

<b><i>Objective:</i></b> DiGeorge syndrome (DGS) is associated with microdeletions of chromosome 22q11. It is the second most common cause of congenital heart disease and is an important consideration whenever a conotruncal cardiac anomaly is identified. The availability of noninvasive prenatal testing (NIPT) is altering the practice of prenatal genetics and maternal-fetal medicine, resulting in a decline in invasive testing. Antenatal ultrasound and other biomarkers have their own limitation. NIPT was proposed to screen DGS with cell-free DNA in Taiwan. Here, we present our experience of prenatal diagnosis of DGS in our center. <b><i>Methods:</i></b> This was a retrospective study between November 1, 2019, and August 31, 2020, in Taiwan. Data were collected from 7,826 pregnant women self-referred for DGS screening with massive parallel shotgun sequencing-based NIPT. High-risk cases subsequently received amniocentesis for array comparative genomic hybridization (aCGH) to confirm the diagnosis. Characteristics of pregnancies were documented when participants received the test. Report of NIPT was completed 2 weeks after the test. Follow-up on high-risk cases was completed by telephone interview on January 30, 2021. <b><i>Results:</i></b> Thirteen cases showed high risk by NIPT, and 7 cases were confirmed by aCGH. The sensitivity and specificity were 100% (95% confidence interval [CI] 64.57–100.00%) and 99.92% (95% CI 99.83–99.96%). The prevalence of DGS was 1 in 1,118 pregnancies. The positive predictive rate was 53.85% (95% CI 29.14–76.79%). One true positive (TP) showed US anomaly, and 5 TPs selected termination. <b><i>Discussion/Conclusion:</i></b> NIPT demonstrated good performance in DGS screening. Detection of 22q11.2 deletion could be combined with routine screening to facilitate proper intervention.

Antioxidant therapy in a patient with Hyperprolinemia type I presented with mild neuromotor retardation and speech disturbance

Background: Hyperprolinemia type 1 (HPI) is an autosomal recessive inborn disease caused by mutations/deletions of PRODH gene, which is located on chromosome 22q11. The clinic spectrum involves mainly delayed psychomotor development, mild-to-severe mental retardation, neuropsychiatric symptoms and epilepsy. Although HPI can easily be diagnosed in patients undergoing metabolic screening tests, there is no effective therapy protocol in use. There are studies showing that it does most of its clinical findings by disrupting mitochondria function. Case report: We present a long-term follow-up of a four-year-old girl with mild neuromotor retardation and speech disturbance, diagnosed with HPI and treated with antioxidant therapy (vitamin C, CoenzymeQ10, vitamin B complex and L-carnitine) for six years. It has been shown that antioxidant therapy decreases proline levels properly and provides clinical improvement.

The Role of Alpha-Synuclein and Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders

Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson’s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Here, we focus on clinico-genetic studies of causal variants and overlapping clinical and cellular features of ASD and PD. Several genes and genomic regions were selected for our review, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence the development of both ASD and PD, with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes, which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches. We propose to re-conceptualize how we understand these disorders and provide a new angle into disease targets and mechanisms linking neurodevelopmental disorders and neurodegeneration.

The Role of Alpha-Synuclein And Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders

Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson&rsquo;s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Here, we focus on clinico-genetic studies of causal variants and overlapping clinical and cellular features of ASD and PD. Several genes and genomic regions were selected for our review, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence development of both ASD and PD with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches. We propose to re-conceptualize how we understand these disorders and provide a new angle into disease targets and mechanisms linking neurodevelopmental disorders and neurodegeneration.

Chromosome 22q11 deletion in a patient with pulmonary atresia, intact ventricular septum, and confluent branch pulmonary arteries

In this study, we report a patient with pulmonary atresia with intact ventricular septum (PA/IVS), confluent pulmonary arteries supplied by an arterial duct, and chromosome 22q11.2 microdeletion. The 22q11.2 deletion syndrome has been associated with anomalies of the outflow tracts, such as tetralogy of Fallot with either pulmonary stenosis or atresia, but we are aware of a solitary case described with pulmonary atresia when the ventricular septum is intact. The presence of genetic malformations can have long-term co-morbidities. By describing our patient, we aim to create awareness of this rare association.