Search Results (3)

Since phosphate is indispensable for skeletal mineralization, chronic hypophosphatemia causes rickets and osteomalacia. Fibroblast growth factor 23 (FGF23), which is mainly produced by osteocytes in bone, functions as the central regulator of phosphate metabolism by increasing the renal excretion of phosphate and suppressing the production of 1,25-dihydroxyvitamin D. The excessive action of FGF23 results in hypophosphatemic diseases, which include a number of genetic disorders such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). Phosphate-regulating gene homologous to endopeptidase on the X chromosome (PHEX), dentin matrix protein 1 (DMP1), ectonucleotide pyrophosphatase phosphodiesterase-1, and family with sequence similarity 20c, the inactivating variants of which are responsible for FGF23-related hereditary rickets/osteomalacia, are highly expressed in osteocytes, similar to FGF23, suggesting that they are local negative regulators of FGF23. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by cleavage-resistant variants of FGF23, and iron deficiency increases serum levels of FGF23 and the manifestation of symptoms in ADHR. Enhanced FGF receptor (FGFR) signaling in osteocytes is suggested to be involved in the overproduction of FGF23 in XLH and autosomal recessive hypophosphatemic rickets type 1, which are caused by the inactivation of PHEX and DMP1, respectively. TIO is caused by the overproduction of FGF23 by phosphaturic tumors, which are often positive for FGFR. FGF23-related hypophosphatemia may also be associated with McCune-Albright syndrome, linear sebaceous nevus syndrome, and the intravenous administration of iron. This review summarizes current knowledge on the pathogenesis of FGF23-related hypophosphatemic diseases. Full article

The rare nevus sebaceous (NS) syndrome (NSS) includes cortical malformations and drug-resistant epilepsy. Somatic RAS-pathway genetic variants are pathogenetic in NS, but not yet described within the brain of patients with NSS. We report on a 5-year-old boy with mild psychomotor delay. A brown-yellow linear skin lesion suggestive of NS in the left temporo-occipital area was evident at birth. Epileptic spasms presented at aged six months. EEG showed continuous left temporo-occipital epileptiform abnormalities. Brain MRI revealed a similarly located diffuse cortical malformation with temporal pole volume reduction and a small hippocampus. We performed a left temporo-occipital resection with histopathological diagnosis of focal cortical dysplasia type Ia in the occipital region and hippocampal sclerosis type 1. Three years after surgery, he is seizure-and drug-free (Engel class Ia) and showed cognitive improvement. Genetic examination of brain and skin specimens revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. Literature review suggests epilepsy surgery in patients with NSS is highly efficacious, with 73% probability of seizure freedom. The few histological analyses reported evidenced disorganized cortex, occasionally with cytomegalic neurons. This is the first reported association of a KRAS genetic variant with cortical malformations associated with epilepsy, and suggests a possible genetic substrate for hippocampal sclerosis. Full article

Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous disorder. It is characterized by the presence of nevus sebaceous, ocular anomalies, neurological deficits, and convulsion. Renal involvement was not commonly reported. We report a 10-year-old girl with LNSS who had concomitant cystic kidney disease and diffuse aortopathy with bilateral renal artery stenosis, leading to hypertension requiring oral anti-hypertensive medications. The girl presented with chorioretinal coloboma and multiple nevus sebaceous at birth. She had aortic coarctation and received surgical repair at one week of life. She had persistent hypertension during her follow-up. Further investigations were performed to look for causes of hypertension apart from possible re-coarctation. Her magnetic resonance angiogram revealed diffuse aortopathy, which extended from the aortic arch to the abdominal aorta. Branches of the aorta, including the celiac trunk, superior mesenteric arteries, and renal arteries, were also narrowed. Multiple renal cysts were also identified in her right kidney. Interventional angioplasty over the renal arteries was not feasible due to diffuse narrowing of the aorta, especially at the origins of renal arteries. The blood pressure was controlled with oral anti-hypertensive medications. Our case illustrated that pediatricians should be aware of the possible renal involvements in LNSS, which impose a significant impact on the management and long-term prognosis of these patients. Full article