Twin girls with hypophosphataemic rickets and papilloedema

A 7 year-old twin girl with hypophosphataemic rickets was evaluated for a recent onset of mild strabismus.She was a homozygous twin sister with hypophosphataemic rickets diagnosed at the age of 2 years, with a mutation in intron 21 of the PHEX gene, which was also present in her sister.The girls' clinical histories were remarkable for an important lower limb varus that progressively improved after starting phosphate supplementation with a galenical solution (Joulies solution 1 mmol phosphate/ml) and vitamin D 1,25 OH.During the examinations, both girls were in good general condition. Physical examinations were unremarkable, except for tibial varus, bilateral fifth finger clinodactyly and bilateral syndactyly of the third and fourth foot fingers. No major head shape abnormalities were noticeable except for a high forehead.One patient presented with a slight strabismus, normal isochoric isocyclic and reactive pupils, no signs of cranial nerve deficit, and no alterations in the rest of the neurological examination. An ophthalmological evaluation showed bilateral papilloedema. A cerebral MRI scan was then performed, suspecting elevated intracranial pressure (figure 1). The same examination was performed on the asymptomatic sister which also demonstrated papilloedema with similar findings on cranial MRI too. edpract;archdischild-2020-319615v1/BLKF1F1BLK_F1Figure 1Sagittal MR T1-weighted imaging shows a 12 mm cerebellar tonsillar herniation (shown by the white arrow) and bulb-medullary junction herniation. The apex of the epistropheus tooth almost reaches the occipital clivus (shown by the white line) and imprints the bulb. QUESTIONS: Which is the most likely diagnosis?CraniosynostosisPseudotumor cerebriDrusenArnold-Chiari malformationHow should these patients be managed?Acetazolamide treatmentThird to fourth ventricle cystostomyWait and see with periodical visual evoked potential follow-upNeurosurgeryHow should patients with X linked hypophosphataemic rickets (XLH rickets) be managed for the risk of craniosynostosis?Monitor cephalic anthropometric measuresPerform a MRI scan if clinical signs of craiosynostosis or intracranial hypertension are presentPerform a skull X-ray every 2 yearsPerform an MRI scan every 2 years Answers can be found on page 02

Epiphyseal Cleft: A Misleading Radiologic Finding

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TTC5 syndrome: Clinical and molecular spectrum of a severe and recognizable condition.

Biallelic mutations in the TTC5 gene have been associated with autosomal recessive intellectual disability (ARID) and subsequently with an ID syndrome including severe speech impairment, cerebral atrophy, and hypotonia as clinical cornerstones. A TTC5 role in IDs has been proposed based on the physical interaction of TTC5 with p300, and possibly reducing p300 co-activator complex activity, similarly to what was observed in Menke-Hennekam 1 and 2 patients (MKHK1 and 2) carrying, respectively, mutations in exon 30 and 31 of CREBBP and EP300, which code for the TTC5-binding region. Recently, TTC5-related brain malformation has been linked to tubulinopathies due to the function of TTC5 in tubulins' dynamics. We reported seven new patients with novel or recurrent TTC5 variants. The deep characterization of the molecular and phenotypic spectrum confirmed TTC5-related disorder as a recognizable, very severe neurodevelopmental syndrome. In addition, other relevant clinical aspects, including a severe pre- and postnatal growth retardation, cryptorchidism, and epilepsy, have emerged from the reversal phenotype approach and the review of already published TTC5 cases. Microcephaly and facial dysmorphism resulted in being less variable than that documented before. The TTC5 clinical features have been compared with MKHK1 published cases in the hypothesis that clinical overlap in some characteristics of the two conditions was related to the common p300 molecular pathway

Selumetinib side effects in children treated for plexiform neurofibromas: first case reports of peripheral edema and hair color change

Background: Plexiform neurofibromas (PNs) are congenital tumors that affect around 50 % of the subjects with neurofibromatosis type 1. Despite being histologically benign, PNs can grow rapidly, especially in the pediatric age, and cause severe morbidities. In the past, various therapeutic approaches have been proposed to treat these masses, none of which obtained valuable results. Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, has been the first molecule to demonstrate the ability of tackling the growth of PNs. The drug\u2019s most common side effects, which usually are mild or moderate, include gastrointestinal symptoms (diarrhea, abdominal pain), dermatologic manifestations (maculo-papular and acneiform rash, paronychia, mucositis), and various laboratory test abnormalities (elevation of creatine kinase and aminotransferase). Cases presentation: We report two previously undescribed adverse events in pediatric patients: peripheral edema and hair color change. The first case of peripheral edema occurred in a 7-year-old boy affected by a severe form of NF1, after two years of treatment with selumetinib at the standard dose (25 mg/m2twice a day). The edema involved the right leg, and the patient did not complain of pain. The second case of peripheral edema occurred in a 12-year-old girl after six months of therapy with selumetinib at the standard dose, involving her lower left leg. The patient initially complained of pain in that area, but it gradually and spontaneously resolved. In both patients, all the radiological exams, including lymphoscintigraphy, pelvic and abdominal ultrasound, and doppler ultrasound of the affected limb, as well as blood tests, revealed no abnormalities. Hair color change appeared in a 4-year-old boy after six months of therapy at the standard dose. The boy\u2019s hair, whose natural color was dark blonde, became lighter in some areas. Despite the appearance of these side effects, all the patients and their families decided to continue the treatment with selumetinib, in considerations of its clinical benefits. Conclusions: Since the use of selumetinib to treat plexiform neurofibromas is increasing in the pediatric population, clinicians should be aware of its side effects, so to decide whether continuing the treatment, reducing the dose or even interrupting it, when appropriate

Malattie rare a cavallo dell\u2019innovazione: una sfida etica e scientifica

Recent advances in medicine are providing new opportunities to treat rare and complex disorders. Precision therapies are being developed to target molecular processes crucial to the disease pathogenesis. Media often present technological advances raising great hopes. However, the journey on the road of medical innovation can be extremely bumpy for some patients. Indeed, subjects living during a period of innovation and medical changes may just face failures, both in terms of frustrated hopes as well as suffering. Indeed, novel treatments do not always lead to a cure for the disease and the choice to join a clinical trial with innovative medications can be hardly challenging, both as concerns science and humanism. The paper describes four stories of children with rare disorders who had different outcomes and discusses how difficult the best scientific and ethical choices can be when novel treatments are proposed

Imaging of empyema (EMP) in children: How bedside ultrasonography (US) impact on clinical practice?

Imaging plays a central role in the diagnosis and management of childhood EMP. Although recent literature recommend the use of US as the central imaging investigation, its use is not as widespread as traditional radiology

Child with a non-painful red scrotum

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Inflammation profile of four early onset Crohn patients.

Crohn disease (CD) is a multifactorial disorder affecting mainly young adults. Sometimes, however, it can present in the first year of life (Early onset Crohn disease (EOCD)) showing an unpredictable course and can often be more severe than at older ages. Some cases have been associated to an underlying primary immunodeficiency such as IL10R deficiency. We studied the functional response to IL-10 and the genotype of IL-10 receptor in four patients with early onset crohn-like colitis. We found an IL10R variant, which may be associated with a decreased response to the cytokine in one patient. Further studies to determine its pathogenic effect should be performed. In addition IL-10 mediated inhibition of LPS-induced TNF\u3b1 expression was measured in patient's monocytes

Inflammation profile of four early onset Crohn patients

Crohn disease (CD) is a multifactorial disorder affecting mainly young adults. Sometimes, however, it can present in the first year of life (Early onset Crohn disease (EOCD)) showing an unpredictable course and can often be more severe than at older ages. Some cases have been associated to an underlying primary immunodeficiency such as IL10R deficiency. We studied the functional response to IL-10 and the genotype of IL-10 receptor in four patients with early onset crohn-like colitis. We found an IL10R variant, which may be associated with a decreased response to the cytokine in one patient. Further studies to determine its pathogenic effect should be performed. In addition IL-10 mediated inhibition of LPS-induced TNFα expression was measured in patient's monocytes