Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism

2020 ◽  
Vol 33 (7) ◽  
pp. 963-966
Author(s):  
Haruka Kawamura ◽  
Satoshi Watanabe ◽  
Takashi I ◽  
Izumi Asahina ◽  
Hiroyuki Moriuchi ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Therapeutic Potential ◽  
Giant Cells ◽  
Efficacy And Safety ◽  
Autosomal Dominant Disorder ◽  
Osteolytic Lesions ◽  
Case Presentation ◽  
Childhood Growth ◽  
Receptor Activator ◽  
Denosumab Treatment

AbstractBackgroundDenosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand, which strongly suppresses osteoclasts. Cherubism is a rare autosomal dominant disorder characterized by symmetrical swelling of the jaws, in which the bone is replaced by a fibrous granuloma containing osteoclast-like giant cells.Case presentationWe report the efficacy and safety of denosumab treatment in a prepubertal boy with progressive cherubism. The treatment consisting of eight subcutaneous denosumab injections (120 mg/dose) in 6 months not only suppressed the expansion of the osteolytic lesions but also dramatically ossified them. However, a transiently decreased growth rate and rebounded asymptomatic hypercalcemia were associated with the treatment.ConclusionsThe present case demonstrated the therapeutic potential of denosumab for treatment of cherubism, although adverse effects, especially those on childhood growth, remain obscure. Further studies are needed to establish a safe and effective protocol for denosumab treatment of children.

scholarly journals Prenatal Diagnosis of Holt–Oram Syndrome With a Novel Mutation of TBX5 Gene: A Case Report

2021 ◽  
Vol 9 ◽  
Author(s):  
Guan-nan He ◽  
Xue-yan Wang ◽  
Min Kang ◽  
Xi-min Chen ◽  
Na Xi ◽  
...  
Keyword(s):  
Septal Defect ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Splice Donor ◽  
Autosomal Dominant Disorder ◽  
Cubitus Valgus ◽  
Case Presentation ◽  
Whole Exome ◽  
The Right ◽  
Tbx5 Gene

Background: Holt–Oram syndrome (HOS) is an autosomal dominant disorder caused by mutations of TBX5 gene.Case presentation: We report a fetus with HOS diagnosed sonographically at 23 weeks of gestation. The fetal parents are non-consanguineous. The fetus exhibited short radius and ulna, inability to supinate the hands, absence of the right thumb, and heart ventricular septal defect (VSD), while the fetal father exhibited VSD and short radius and ulna only. Fetal brother had cubitus valgus and thumb adduction, except for VSD, short radius and ulna. The pregnancy was terminated. Whole-exome sequencing (WES) revealed a novel mutation in the TBX5 (c.510+1G>A) in the fetus inherited from the father. The variant (c.510+1G>A) occurs at splice donor and may alter TBX5 gene function by impact on splicing. It was not previously reported in China.Conclusion: Our case reported a novel mutation in TBX5, which expanded the known genetic variants associated with HOS.

scholarly journals Diagnosis of hereditary hemorrhagic telangiectasia in a pediatric patient admitted with diabetes: the utility of genetic testing

2021 ◽  
Vol 2 (3) ◽  
pp. 01-02
Author(s):  
Alvaro E. Galvis ◽  
Beatrice Batoczki ◽  
Iris S. Pecson ◽  
Evan Vidal ◽  
Craig T. Nakamura
Keyword(s):  
Genetic Testing ◽  
Pediatric Patient ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Autosomal Dominant ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Autosomal Dominant Disorder ◽  
Case Presentation ◽  
History Of ◽  
Vascular Dysplasia

Background: Hereditary hemorrhagic telangiectasia (HHT) formerly known as Osler-Weber-Rendu syndrome is a rare autosomal dominant disorder characterized by vascular dysplasia and a wide spectrum of clinical manifestations. Case presentation: We report the case of an undiagnosed pediatric patient who presented hypoxemia on clinical exam as the only suggestive feature for the presence of HHT. Conclusions: Although HHT diagnosis is based on the finding of characteristic clinical features genetic testing should also be implemented when a family history of the disease is present to help confirm or refute the diagnosis.

Sclerosi tuberosa ed everolimus: una nuova storia

2021 ◽  
Vol 40 (7) ◽  
pp. 443-449
Author(s):  
Chiara Cervesi ◽  
Giulia Maria Di Marzio ◽  
Valentina Kiren ◽  
Elisabetta Cattaruzzi ◽  
Paola Costa ◽  
...  
Keyword(s):  
Mtor Inhibitor ◽  
Autosomal Dominant ◽  
Treatment Options ◽  
Giant Cells ◽  
Treatment Recommendation ◽  
Malignant Neoplasms ◽  
Behavioural Disorders ◽  
Autosomal Dominant Disorder ◽  
The Individual ◽  
Definite Role

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder, due to inactivating muta-tions of TSC1 or TSC2 mTOR pathway genes and is characterized by variable multisystem manifestations ranging from hamartomas to malignant neoplasms. It frequently associated to seizures, intellectual disability and behavioural disorders. Surgical treatment has traditionally been used to manage subependymal giant cells astrocytomas (SEGA). The introduction of mTOR inhibitor rapamycin, with its definite role both as primary and as adjuvant treatment, has significantly modified the management opportunities in the clinical practice. It is important to consider both treatment options in a balanced way and not only the SEGA, but also the individual patient and their associated comorbidities. The pros and the cons of both options should be discussed by a multidisciplinary team before establishing an individualized treatment recommendation. The paper reports the case of a patient with an asymptomatic SEGA who was treated with everolimus. The treatment was effective in reducing the size of the tumour, it was safe and well tolerated.

scholarly journals Fibrodysplasia ossificans progressiva (stone man syndrome): a case report

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Zakir Ali Shah ◽  
Sascha Rausch ◽  
Uzma Arif ◽  
Bilal El Yafawi
Keyword(s):  
Early Diagnosis ◽  
Heterotopic Ossification ◽  
Autosomal Dominant ◽  
Surgical Intervention ◽  
Surgical Excision ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Test Results ◽  
Autosomal Dominant Disorder ◽  
Case Presentation

Abstract Background Fibrodysplasia ossificans progressiva is an ultrarare autosomal dominant disorder and disabling syndrome characterized by postnatal progressive heterotopic ossification of the connective tissue and congenital malformation of the big toes. Fibrodysplasia ossificans progressiva has worldwide prevalence of about 1 in 2 million births. Nearly 90% of patients with fibrodysplasia ossificans progressiva are misdiagnosed and mismanaged and thus undergo unnecessarily interventions. So far, the number of reported existing cases worldwide is about 700. Clinical examination, radiological evaluation, and genetic analysis for mutation of the ACVR1 gene are considered confirmatory tools for early diagnosis of the disease. Association of fibrodysplasia ossificans progressiva with heterotopic ossification is well documented; however, postsurgical exaggerated response has never been reported previously, to the best of our knowledge. Case presentation We report a case of a 10-year-old Pakistani boy brought by his parents to our institution. He had clinical and radiological features of fibrodysplasia ossificans progressive and presented with multiple painful lumps on his back due to hard masses and stiffness of his shoulders, neck, and left hip. He underwent surgical excision of left hip ossification followed by an exaggerated response in ossification with early disability. Radiological examination revealed widespread heterotopic ossification. All of his laboratory blood test results were normal. Conclusion Fibrodysplasia ossificans progressiva is a very rare and disabling disorder that, if misdiagnosed, can lead to unnecessary surgical intervention and disastrous results of early disability. We need to spread knowledge to physicians and patients’ family members about the disease, as well as its features for early diagnosis and how to prevent flare-up of the disease to promote better quality of life in these patients.

scholarly journals Extracellular vesicles and exosomes generated from cystic renal epithelial cells promote cyst growth in autosomal dominant polycystic kidney disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hao Ding ◽  
Linda Xiaoyan Li ◽  
Peter C. Harris ◽  
Junwei Yang ◽  
Xiaogang Li
Keyword(s):  
Kidney Disease ◽  
Epithelial Cells ◽  
Polycystic Kidney Disease ◽  
Extracellular Vesicles ◽  
Autosomal Dominant ◽  
Therapeutic Potential ◽  
Polycystic Kidney ◽  
Renal Epithelial Cells ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cyst Growth

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is caused by germline mutations of PKD1 or PKD2 on one allele and a somatic mutation inactivating the remaining normal allele. However, if and how null ADPKD gene renal epithelial cells affect the biology and function of neighboring cells, including heterozygous renal epithelial cells, fibroblasts and macrophages during cyst initiation and expansion remains unknown. Here we address this question with a “cystic extracellular vesicles/exosomes theory”. We show that cystic cell derived extracellular vesicles and urinary exosomes derived from ADPKD patients promote cyst growth in Pkd1 mutant kidneys and in 3D cultures. This is achieved by: 1) downregulation of Pkd1 gene expression and upregulation of specific miRNAs, resulting in the activation of PKD associated signaling pathways in recipient renal epithelial cells and tissues; 2) the activation of fibroblasts; and 3) the induction of cytokine expression and the recruitment of macrophages to increase renal inflammation in cystic kidneys. Inhibition of exosome biogenesis/release with GW4869 significantly delays cyst growth in aggressive and milder ADPKD mouse models, suggesting that targeting exosome secretion has therapeutic potential for ADPKD.

Autosomal Dominant Frontotemporal Lobar Degeneration in a Filipino Family with Progranulin Mutation

2021 ◽  
pp. 1-8
Author(s):  
Jacqueline Dominguez ◽  
Arlene Ng ◽  
Jeryl Yu ◽  
Anne Cristine Guevarra ◽  
Maria Luisa Daroy ◽  
...  
Keyword(s):  
Frontotemporal Lobar Degeneration ◽  
White Matter Hyperintensities ◽  
Autosomal Dominant ◽  
The Philippines ◽  
Vascular Risk ◽  
Case Presentation ◽  
Nonfluent Aphasia ◽  
Protein Tau ◽  
Review Reports ◽  
Progressive Nonfluent Aphasia

<b><i>Background:</i></b> Compared to Western populations, familial frontotemporal lobar degeneration (FTLD) is rare among Asians. Progranulin (GRN) gene mutation, which is a major cause of FTLD, is likewise rare. We present a family with FTLD from the Philippines with an autosomal dominant pattern of inheritance and GRN mutation and briefly review reports of GRN mutations in Asia. <b><i>Case Presentation:</i></b> The proband is 66 years old with progressive nonfluent aphasia (PNFA)-corticobasal syndrome . We assessed 3 generations of her pedigree and found 11 affected relatives with heterogenous phenotypes, usually behavioral variant frontotemporal dementia (FTD) and PNFA. Neuroimaging showed atrophy and hypometabolism consistent with FTD syndromes. White matter hyperintensities were seen in affected members even in the absence of vascular risk factors. A GRN mutation R110X was found in 6 members, 3 with symptoms and 3 were asymptomatic. Plasma GRN was low (&#x3c;112 ng/mL) in all mutation carriers. No mutations were found in microtubule-associated protein tau, APP, PSEN1, and PSEN2 genes, and all were APOE3. <b><i>Conclusion:</i></b> This is the first Filipino family with autosomal dominant FTD documented with GRN mutation. Identifying families and cohorts would contribute to therapeutic developments in an area with FTD-GRN.

scholarly journals Anti-IL17 antibody Secukinumab therapy is associated with ossification in giant cell tumor of bone: a case report of pathologic similarities and therapeutic potential similar to Denosumab

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Andrew Chandler ◽  
Meredith K. Bartelstein ◽  
Tomohiro Fujiwara ◽  
Cristina R. Antonescu ◽  
John H. Healey ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Therapeutic Potential ◽  
Quantitative Polymerase Chain Reaction ◽  
Treatment Method ◽  
Giant Cells ◽  
Cell Tumor ◽  
Pcr Analysis ◽  
Increased Risk

Abstract Background Giant cell tumor of bone is a benign, locally aggressive neoplasm. Surgical resection is the preferred treatment method. However, for cases in which resection poses an increased risk to the patient, denosumab (anti-RANKL monoclonal antibody) is considered. Secukinumab is an anti-IL-17 antibody that is used in psoriatic arthritis to reduce bone resorption and articular damage. Case presentation One case of giant cell tumor of bone (GCTB) in a patient treated with secukinumab for psoriatic arthritis demonstrated findings significant for intra-lesional calcifications. Histologic examination showed ossification, new bone formation, and remodeling. A paucity of osteoclast type giant cells was noted. Real-time quantitative polymerase-chain-reaction (qRT-PCR) analysis revealed decreased osteoclast function compared to treatment-naive GCTB. Conclusions Secukinumab may play a role in bone remodeling for GCTB. Radiologists, surgeons, and pathologists should be aware of this interaction, which can cause lesional ossification. Further research is required to define the therapeutic potential of this drug for GCTB and osteolytic disease.

PLEXIFORM NEUROFIBROMA OF THE BRACHIAL PLEXUS – A RARE CASE REPORT

2021 ◽  
pp. 13-15
Author(s):  
Surya Rao Rao Venkata Mahipathy ◽  
Alagar Raja Durairaj ◽  
Narayanamurthy Sundaramurthy ◽  
Anand Prasath Jayachandiran ◽  
Suresh Rajendran
Keyword(s):  
Brachial Plexus ◽  
Rare Case ◽  
Autosomal Dominant ◽  
Plexiform Neurofibroma ◽  
Autosomal Dominant Disorder ◽  
Surgical Debulking ◽  
Rare Case Report ◽  
Benign Tumours ◽  
Common Benign Tumour

Neurobroma is a common benign tumour occurring as part of an autosomal dominant disorder, neurobromatosis type 1, leading to the formation of benign tumours or neurobromas of the peripheral nervous system. Large neurobromas of the brachial plexus are rare and present a difcult challenge for surgeon due to the anatomical complexity of the brachial plexus. Dermal neurobromas usually present with swelling and occasional pain, but neurobromas associated with the brachial plexus present with pain and neurological symptoms. These plexiform neurobromas of the brachial plexus are known to undergo malignant transformation. Here, we present a case of a large plexiform neurobroma affecting the left brachial plexus and extending till the elbow, conrmed with MRI and surgical debulking was done.

Progressive Diaphyseal Dysplasia: Genetics and Clinical and Radiologic Manifestations

PEDIATRICS ◽  
1984 ◽  
Vol 74 (3) ◽  
pp. 399-405
Author(s):  
Yehezkel Naveh ◽  
Joseph K. Kaftori ◽  
Uri Alon ◽  
Jacob Ben-David ◽  
Moshe Berant
Keyword(s):  
Autosomal Dominant ◽  
Autosomal Dominant Disorder ◽  
Generation Family ◽  
Progressive Diaphyseal Dysplasia ◽  
Radiographic Screening ◽  
Osteosclerotic Dysplasia ◽  
Structural Deformity ◽  
Diaphyseal Dysplasia ◽  
Engelmann Disease

Progressive diaphyseal dysplasia was found in a three-generation family including 13 affected individuals, the largest family reported to date. Our study confirms that progressive diaphyseal dysplasia, also known as Engelmann's or Camurati-Engelmann disease, is an autosomal dominant disorder with variable osseous and muscular manifestations. Disease distribution among patients, within a given patient, or even in individual bones is unpredictable. The femur is the most commonly and severely affected bone and hence most useful for radiographic screening of possible patients. Radiographs provide a meaningful assessment of disease activity and extent. The severity of symptoms is generally proportionate to severity of involvement shown by roentgenography. Exophthalmos due to osteosclerotic dysplasia of the skull occurred in more than half of the patients with progressive diaphyseal dysplasia. Twelve-year follow-up of this family, with affected individuals ranging in age from 6 months to 12 years, indicates that progressive diaphyseal dysplasia may progress or become quiescent and be remarkably inactive despite advanced osteosclerosis and structural deformity.

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