ECAD study: Evaluating agreement degree among paediatricians in hip dysplasia assessment by the Graf ultrasound method.

Developmental dysplasia of the hip (DDH) is the most common musculoskeletal anomaly of childhood. This study analyses paediatrician's concordance performing hip ultrasound according to Graf's method. An analytical cross-sectional study is designed. Patients' hips are evaluated by Graf's ultrasound method at 4-6 and 12-16 weeks of age. Demographic characteristics, pregnancy history, factors related to DDH, hip type, and α and ß angles are collected. To assess the agreement degree of hip diagnosis and hip types Kappa index (I. kappa) is used. Intraclass correlation coefficient (ICC) evaluates the concordance of α and ß angles. A p value < 0.05 is considered statistically significant. All results are represented with their 95% confidence interval (95% CI). Four hundred sixty-seven neonates are recruited and meet the inclusion criteria. A total of 3182 images were analysed. Agreement between paediatricians according to hip diagnosis and different types ranges from moderate to almost perfect I. kappa 0.6-1.0 (95% CI 0.5-0.7; 95% CI 1.0-1.0). α angle ICC for paediatricians is between 0.75 and 0.88 (95% CI 0.61-0.86; 95% CI 0.80-0.92). ß angle value agreement degree among paediatricians at both visits is moderate. The Graf method is the most popular ultrasound technique for hip assessment. In our setting, paediatricians carry out children follow-up; therefore, they should perform universal screening. In this study agreement degree between paediatricians varies between substantial and almost perfect. Conclusion: The Graf ultrasound procedure performed by paediatricians is a reliable test and can be used for DDH screening. What is Known • Developmental dysplasia of the hip (DDH) is the most common congenital musculoskeletal anomaly of childhood. Early diagnosis and treatment improve DDH prognosis. Lack of detection can cause complications such as lameness, early osteoarthritis and need for hip replacement at an early age. What is New • Today, the best screening method is still subject of debate. But it seems that with selective screening many pathological hips go unnoticed. Universal screening implementation may be a challenge in some countries. But the question is if this could be carried out by paediatricians as part of healthy child follow-up.

The clinical and biochemical hallmarks generally associated with GLUT1DS may be caused by defects in genes other than SLC2A1.

Glucose transporter 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder caused by haploinsufficiency of the GLUT1 glucose transporter (encoded by SLC2A1) leading to defective glucose transport across the blood-brain barrier. This work describes the genetic analysis of 56 patients with clinical or biochemical GLUT1DS hallmarks. 55.4% of these patients had a pathogenic variant of SLC2A1, and 23.2% had a variant in one of 13 different genes. No pathogenic variant was identified for the remaining patients. Expression analysis of SLC2A1 indicated a reduction in SLC2A1 mRNA in patients with pathogenic variants of this gene, as well as in one patient with a pathogenic variant in SLC9A6, and in three for whom no candidate variant was identified. Thus, the clinical and biochemical hallmarks generally associated with GLUT1DS may be caused by defects in genes other than SLC2A1.

Complexity of the Hereditary Motor and Sensory Neuropathies: Clinical and Cellular Characterization of the MPZ p.D90E Mutation.

Early-onset hereditary motor and sensory neuropathies are rare diseases representing a broad clinical and genetic spectrum. Without a notable familial history, the clinical diagnosis is complicated because acquired causes of peripheral neuropathy, such as inflammatory neuropathies, neuropathies with toxic causes, and nutritional deficiencies, must be considered. We examined the clinical, electrophysiological, and pathologic manifestations of a boy with an initial diagnosis of chronic inflammatory demyelinating polyneuropathy. The progression of the disease despite treatment led to a suspicion of hereditary motor and sensory neuropathy. Genetic testing revealed the presence of the MPZ p.D90E mutation in heterozygosis. To clarify the pathogenicity of this mutation and achieve a conclusive diagnosis, we investigated the MPZ p.D90E mutation through in silico and cellular approaches. This study broadens the clinical phenotype of hereditary motor and sensory neuropathy due to MPZ mutation and emphasises the difficulty of achieving an accurate genetic diagnosis in a sporadic patient to provide an appropriate pharmacologic treatment.