BackgroundEarly diagnosis of girls with Turner syndrome (TS) is essential to provide timely intervention and support. The screening guidelines for TS suggest karyotype evaluation in patients presenting with short stature, webbed neck, lymphoedema, coarctation of aorta or ≥ two dysmorphic features. The aim of the study was to determine the age and clinical features at the time of presentation and to identify potential delays in diagnosis of TS.MethodsRetrospective data on age at diagnosis, reason for karyotype analysis and presenting clinical features was collected from the medical records of 67 girls with TS.ResultsThe mean age of diagnosis was 5.89 (±5.3) years ranging from pre-natal to 17.9 years (median 4.6 years). 10% were diagnosed antenatally, 16% in infancy, 54% in childhood (1–12 years) and 20% in adolescence (12–18 years). Lymphoedema (27.3%) and dysmorphic features (27.3%) were the main signs that triggered screening in infancy. Short stature was the commonest presenting feature in both childhood (52.8%) and adolescent (38.5%) years. At least 12% of girls fulfilled the criteria for earlier screening but were diagnosed only at a later age (mean age = 8.78 years). 13.4% of patients had classical 45XO karyotype and 52.3% of girls had a variant karyotype.ConclusionMajority of girls with TS were diagnosed only after the age of 5 years. Short stature triggered evaluation for most patients diagnosed in childhood and adolescence. Lack of dedicated community height-screening programme to identify children with short stature and lack of awareness could have led to potential delays in diagnosing TS. New strategies for earlier detection of TS are needed.

X-linked hypophosphataemia (XLH) is caused by a pathogenic variant in the PHEX gene, which leads to elevated circulating FGF23. High FGF23 causes hypophosphataemia, reduced active vitamin D concentration and clinically manifests as rickets in children, and osteomalacia in children and adults. Conventional therapy for XLH includes oral phosphate and active vitamin D analogues but does not specifically treat the underlying pathophysiology of elevated FGF23-induced hypophosphataemia. In addition, adherence to conventional therapy is limited by frequent daily dosing and side effects such as gastrointestinal symptoms, secondary hyperparathyroidism and nephrocalcinosis. Burosumab, a recombinant human IgG1 monoclonal antibody that binds to and inhibits the activity of FGF23, is administered subcutaneously every 2 weeks. In clinical trials (phase 2 and 3) burosumab was shown to improve phosphate homeostasis, that consequently resolves the skeletal/non-skeletal manifestations of XLH. Burosumab was licensed in Europe (February 2018) with NICE approving use within its marketing authorisation in October 2018. In this publication, the British Paediatric and Adolescent Bone Group (BPABG), reviewed current evidence and provides expert recommendations for care pathway and management of XLH with burosumab.

Background: Raine syndrome (RS) is a rare autosomal recessive disorder caused by biallelic loss-of-function mutations of FAM20C. The most common clinical features are microcephaly, exophthalmos, hypoplastic nose and severe midface hypoplasia, leading to choanal atresia. The radiological findings include generalized osteosclerosis and brain calcifications. RS is usually lethal during the neonatal period due to severe respiratory distress. However, there exists a non-lethal RS form, the phenotype of which is extremely heterogeneous. There is paucity of data about clinical course and life expectancy of these patients. Results: This is the first description of follow-up features of non-lethal RS patients. Moreover, we present three unpublished cases. There are five Asian and two Arab patients. All were born to consanguineous parents. The most common neonatal comorbidity was respiratory distress secondary to choanal atresia. A variable degree of neurodevelopmental delay was seen in the majority of our cases and seizures and hearing or vision involvement were also frequent. Neurological and orthopedic issues were the most frequent complications seen at follow-up in our group. Persistent hypophosphatemic rickets was the most striking endocrinological manifestation, which was scarcely responsive to therapy with phosphate salts and alfacalcidol. Life expectancy of our patients goes beyond childhood, with the oldest of those described being 18 years old at present. Conclusions: Manifestations of RS in those surviving the neonatal period are being increasingly recognized. Our study supports previous findings and provides clinical and biochemical observations and data from longer follow up. Finally, we propose multidisciplinary follow up for patients with non-lethal RS.

No abstract

No abstract