Low muscle volume of the anal sphincter complex: A novel prognostic factor in children with anorectal malformations?

BACKGROUND/PURPOSE: The anal sphincter complex (ASC) plays a key role in continence and is often dysfunctional in infants born with anorectal malformations (ARM). The ASC is well depicted by magnetic resonance (MR) imaging but volumetric reference data are lacking in infants. Thus, we tested the feasibility of MR based ASC volumetry, collected reference data, and compared them with cases of favorableprognosis and unfavorable prognosis (as defined by the type of ARM). METHODS: We determined ASC volume on T2 weighted MR images of seventy six infants (ARM n = 33; controls n = 43) by manual segmentation. Inter operator agreement was assessed by intraclass correlation coefficient. Linear regression was used to establish weight dependent reference data. Observed to expected ASC volumes of patients with unfavorable and favorable prognosis were compared (unpaired t test). RESULTS: ASC volumetry was feasible in all cases. Patients with ARM had low 'observed to expected' ASC volume ( 18.1%; p = 0.006). 'Observed to expected' ASC volume differed significantly between patients with favorableand unfavorable prognosis (p < 0.001). CONCLUSION: We confirmed the feasibility of MRI based ASC volumetry and provided initial reference data for infants. Although ASC volumes were lowest in infants with ARM of unfavorable prognosis for fecal continence, the value of ASC volume as prognostic parameter remains to be determined.

Incomplete penetrance of a novel SDHD variation causing familial head and neck paraganglioma.

OBJECTIVE: Identification of variations in tumour suppressor genes encoding the tetrameric succinate dehydrogenase (SDHx) mitochondrial enzyme complex may lead to personalised therapeutic concepts for the orphan disease, familial paraganglioma (PGL) type 1-5. We undertook to determine the causative variation in a family suffering from idiopathic early-onset (22 ± 2 years) head and neck PGL by PCR and Sanger sequencing. DESIGN: Prospective genetic study. SETTING: Tertiary Referral Otolaryngology Centre. PARTICIPANTS: Twelve family members. MAIN OUTCOME MEASURES: Main outcomes were clinical analysis and SDH genotyping RESULTS AND CONCLUSIONS: A novel heterozygous c.298delA frameshift variation in exon 3 of SDH subunit D (SDHD) was associated with a paternal transmission pattern of PGL in affected family members available to the study. Family history over five generations in adulthood indicated a variable penetrance for PGL inheritance in older generations. The c.298delA variant would cause translation of a 34-residue C-terminus distal to lysine residue 99 in the predicted transmembrane domain II of the full-length sequence p.(Thr100LeufsTer35) and would affect the translation products of all protein-coding SDHD isoforms containing transmembrane topologies required for positional integration in the inner mitochondrial membrane and complex formation. These results underly the importance of genetic screening for PGL also in cases of unclear inheritance, and variation carriers should benefit from screening and lifelong follow-up.

Assessment of sacral ratio in patients with anorectal malformations: Can magnetic resonance imaging replace conventional radiograph?

INTRODUCTION: In patients with anorectal malformations (ARM), the sacral ratio (SR) serves as an established predictive marker for functional prognosis and is derived from conventional radiographs. More recently, magnetic resonance imaging (MRI) has emerged as a diagnostic alternative for preoperative/baseline assessment of patients with ARM. With this study we aimed to evaluate if the SR could be reliable be measured from MRI images and if it correlated to SR measurements obtained from radiographs. METHODS: Two raters analyzed MRI data and conventional radiographs from thirty-one subjects (n = 17 with ARM; n = 14 controls). We calculated intra-class correlation coefficients (ICCs) to test inter-rater reliability and applied paired t-tests to examine if SR parameters from MRI were comparable with those from pelvic radiograph. We further computed Pearson's correlation coefficients to test the linear relationship between SR calculated from MRI and conventional radiographs. RESULTS: The ARM and control groups did not statistically differ in their age and weight on the day of the MRI scan. Reliability analysis revealed an excellent inter-rater agreement for SR from radiograph parameters with an intraclass correlation coefficient (ICC) of 0.94, respectively of 0.86 for MRI (frontal plane), and of 0.84 for MRI (sagittal plane). The correlation coefficient between SR calculated from the sagittal MRI and SR calculated from radiograph images was significant and high (r = 0.80, P < 0.001). The SRs from MRI images did not significantly differ from SRs from radiographs, but were also not statistically equivalent. CONCLUSION: Our results demonstrate that the SR can be derived from MRI images with good inter-rater reliability. The SR value is marginal higher when calculated on MRI, presumably due to inclusion of cartilaginous yet unossified structures.

Decreased Compressional Sound Velocity Is an Indicator for Compromised Bone Stiffness in X-Linked Hypophosphatemic Rickets (XLH).

Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. Methods: BDAT bone ultrasound was performed at the non-dominant distal radius (33% relative to distal head) and the central left tibia (50%) in eight XLH patients aged between 4.2 and 20.8 years and compared to twenty-nine healthy controls aged between 5.8 and 22.4 years. In eighteen controls, only radius measurements were performed. Four patients and four controls opted to participate in HR-pQCT scanning of the ultradistal radius and tibia. Results: Bone ultrasound was feasible in patients and controls as young as 4 years of age. The velocity of the first arriving signal (νFAS) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean νFAS of XLH patients and controls was 3599 ± 106 and 3866 ± 142 m/s, respectively (-6.9%; p < 0.001). In the tibia, it was 3578 ± 129 and 3762 ± 124 m/s, respectively (-4.9%; p = 0.006). HR-pQCT showed a higher trabecular thickness in the tibia of XLH patients (+16.7%; p = 0.021). Conclusions: Quantitative bone ultrasound revealed significant differences in cortical bone quality of young XLH patients as compared to controls. Regular monitoring of XLH patients by a radiation-free technology such as BDAT might provide valuable information on bone quality and contribute to the optimization of treatment. Further studies are needed to establish this affordable and time efficient method in the XLH patients.