Prenatal diagnosis of proximal focal femoral deficiency: Literature review of prenatal sonographic findings

Proximal focal femoral deficiency (PFFD) is a rare musculoskeletal malformation that occurs in 0.11-0.2 per 10,000 live births. This congenital anomaly involves the pelvis and proximal femur with widely variable manifestations, from mild femoral shortening and hypoplasia to the absence of any functional femur and acetabular aplasia. Prenatal diagnosis of PFFD is still a challenge, but early recognition of this malformation could provide useful information to both parents and physicians concerning management and therapeutic planning. For this review, we analyzed all the cases of prenatally diagnosed PFFD that were reported in the literature from 1990 to 2014 and provide a description of the most common prenatal sonographic findings

Optimal surgical care for adolescent idiopathic scoliosis: an international consensus

Purpose The surgical management of adolescent idiopathic scoliosis (AIS) has seen many developments in the last two decades. Little high-level evidence is available to support these changes and guide treatment. This study aimed to identify optimal operative care for adolescents with AIS curves between 40° and 90° Cobb angle. Methods From July 2012 to April 2013, the AOSpine Knowledge Forum Deformity performed a modified Delphi survey where current expert opinion from 48 experienced deformity surgeons, representing 29 diverse countries, was gathered. Four rounds were performed: three web-based surveys and a final face-to-face meeting. Consensus was achieved with ≥70 % agreement. Data were analyzed qualitatively and quantitatively. Results Consensus of what constitutes optimal care was reached on greater than 60 aspects including: preoperative radiographs; posterior as opposed to anterior (endoscopic) surgical approaches; use of intraoperative spinal cord monitoring; use of local autologous bone (not iliac crest) for grafts; use of thoracic and lumbar pedicle screws; use of titanium anchor points; implant density of <80 % for 40°–70° curves; and aspects of postoperative care. Variability in practice patterns was found where there was no consensus. In addition, there was consensus on what does not constitute optimal care, including: routine pre- and intraoperative traction; routine anterior release; use of bone morphogenetic proteins; and routine postoperative CT scanning. Conclusions International consensus was found on many aspects of what does and does not constitute optimal operative care for adolescents with AIS. In the absence of current high-level evidence, at present, these expert opinion findings will aid health care providers worldwide define appropriate care in their regions. Areas with no consensus provide excellent insight and priorities for future researchpublished_or_final_versio

Rod Angulation Relationship with Thoracic Kyphosis after Adolescent Idiopathic Scoliosis Posterior Instrumentation

Adolescent idiopathic scoliosis; Predictive medicine; Rod contourEscoliosis idiopática del adolescente; Medicina predictiva; Contorno de varillaEscoliosi idiopàtica de l'adolescent; Medicina predictiva; Contorn de varetaIntroduction: Surgery to correct spinal deformities in scoliosis involves the use of contoured rods to reshape the spine and correct its curvatures. It is crucial to bend these rods appropriately to achieve the best possible correction. However, there is limited research on how the rod bending process relates to spinal shape in adolescent idiopathic scoliosis surgery. Methods: A retrospective study was conducted using a prospective multicenter scoliosis database. This study included adolescent idiopathic scoliosis patients from the database who underwent surgery with posterior instrumentation covering the T4 to T12 segments. Standing global spine X-rays were used in the analysis. The sagittal Cobb angles between T5 and T11 were measured on the spine. Additionally, the curvature of the rods between T5 and T11 was measured using the tangent method. To assess the relationship between these measurements, the difference between the dorsal kyphosis (TK) and the rod kyphosis (RK) was calculated (ΔK = TK − RK). This study aimed to analyze the correlation between ΔK and various patient characteristics. Both descriptive and statistical analyses were performed to achieve this goal. Results: This study encompassed a cohort of 99 patients, resulting in a total of 198 ΔK measurements for analysis. A linear regression analysis was conducted, revealing a statistically significant positive correlation between the kyphosis of the rods and that of the spine (r = 0.77, p = 0.0001). On average, the disparity between spinal and rod kyphosis averaged 5.5°. However, it is noteworthy that despite this modest mean difference, there was considerable variability among the patients. In particular, in 84% of cases, the concave rod exhibited less kyphosis than the spine, whereas the convex rod displayed greater kyphosis than the spine in 64% of cases. It was determined that the primary factor contributing to the flattening of the left rod was the magnitude of the coronal Cobb angle, both before and after the surgical procedure. These findings emphasize the importance of considering individual patient characteristics when performing rod bending procedures, aiming to achieve the most favorable outcomes in corrective surgery. Conclusions: Although there is a notable and consistent correlation between the curvature of the spine and the curvature of the rods, it is important to acknowledge the substantial heterogeneity observed in this study. This heterogeneity suggests that individual patient factors play a significant role in shaping the outcome of spinal corrective surgery. Furthermore, this study highlights that more severe spinal curvatures in the frontal plane have an adverse impact on the shape of the rods in the sagittal plane. In other words, when the scoliosis curve is more pronounced in the frontal plane, it tends to influence the way the rods are shaped in the sagittal plane. This underscores the complexity of spinal deformities and the need for a tailored approach in surgical interventions to account for these variations among patients.This research is funded by the European Spine Study Group

Celiac disease screening in 100 Turkish children with Down syndrome

The aim of this study was to screen a group of children with Down syndrome (DS) for celiac disease, and to define future strategies for screening the patients followed at our center. One hundred children over the age of two years with Down syndrome were serologically screened using antiendomysium antibody (EMA) IgA and serum IgA in order to exclude a concomitant IgA deficiency. Clinical assessment included detailed physical examination, measurement of weight and height plotted on growth charts for DS children followed by an interview of the patients and parents about gastrointestinal symptoms. Only one patient out of 100 (1%) was detected to be EMA IgA-positive. The child's family refused consent for the biopsy procedure. None of the patients had IgA deficiency. Abdominal distention was present in 13 (13%) patients, and anorexia in 9 (9%), vomiting in 7 (7%) and alopecia areata in 2 (2%) patients were also noted. Despite the small number of patients in our group, this result yielding 1% EMA-positivity is the lowest yet determined among DS patients. It has led us to discuss whether or not a change in our screening strategy is necessary

Hypophosphatasia Presenting with Pyridoxine-Responsive Seizures, Hypercalcemia, and Pseudotumor Cerebri: Case Report

Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure. Key words: Hypophosphatasia, pyridoxine-responsive seizures, bisphosphonates, alkaline phosphatase, bone resorption, hypercalcemi

A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategie

Congenital contractural arachnodactyly (Beals syndrome)

Congenital contractural arachnodactyly (Beals syndrome) is an autosomal dominantly inherited connective tissue disorder characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, abnormal pinnae and muscular hypoplasia. It is caused by a mutation in FBN2 gene on chromosome 5q23. Although the clinical features can be similar to Marfan syndrome (MFS), multiple joint contractures (especially elbow, knee and finger joints), and crumpled ears in the absence of significant aortic root dilatation are characteristic of Beals syndrome and rarely found in Marfan syndrome. The incidence of CCA is unknown and its prevalence is difficult to estimate considering the overlap in phenotype with MFS; the number of patients reported has increased following the identification of FBN2 mutation. Molecular prenatal diagnosis is possible. Ultrasound imaging may be used to demonstrate joint contractures and hypokinesia in suspected cases. Management of children with CCA is symptomatic. Spontaneous improvement in camptodactyly and contractures is observed but residual camptodactyly always remains. Early intervention for scoliosis can prevent morbidity later in life. Cardiac evaluation and ophthalmologic evaluations are recommended

Analysis of MTHFR 1298A>C in addition to MTHFR 677C>T polymorphism as a risk factor for neural tube defects in the Turkish population

Maternal folic acid intake in the periconceptional period is strongly related to reduction in recurrence and occurrence of birth defects involving the neural tube. Among the single nucleotide polymorphisms (SNPs) influencing the folate metabolism, the methylenetetrahydrofolate reductase (MTHFR) gene has been the one most exclusively studied. Many studies have reported significant association between MTHFR 677C>T and increased risk of neural tube defects (NTDs). Our previous study did not support this observation. The present study aimed to determine the prevalence of 1298A>C polymorphism in addition to 677C>T in the same Turkish population as a risk factor for NTDs. We genotyped case (95 offspring with NTDs, 80 mothers, 72 fathers) and control (93 healthy children) populations for MTHFR 677C>T and MTHFR 1298 A>C polymorphisms. The comparison demonstrated a significant increase in the 1298AA/677TT genotype frequency among mothers of offspring with NTDs (OR 5.23 [1.06-25.9]; p=0.067). The 677CT genotype was only 1.35 times higher than controls among mothers when 677C>T polymorphism was evaluated alone, while 677CT/1298AC in the current study demonstrated a 3.8 times increase in this risk. These observations led us to conclude that although not statistically significant, MTHFR 1298AC polymorphism might be a risk factor for the occurrence of NTDs in the Turkish population