Efficacy and safety of long-term sirolimus use as part of multidisciplinary care in a pediatric patient with CLOVES syndrome: Case report

2021 ◽  
pp. 1-8
Author(s):  
Alexis Leonard ◽  
Yaser Diab ◽  
Laura L. Tosi
Keyword(s):  
Pediatric Patient ◽  
Medical Therapy ◽  
Vascular Malformations ◽  
Genetic Disorder ◽  
Somatic Mosaicism ◽  
Multidisciplinary Care ◽  
Genu Valgum ◽  
Close Monitoring ◽  
Length Discrepancy ◽  
Functional Gains

BACKGROUND: CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal/spinal) syndrome is a rare and progressive genetic disorder resulting from somatic mosaicism in activating mutations in the phosphatidylinositol-4,5- bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. PIK3CA is a cell growth master regulator where gain of function mutations give rise to abnormal activation of the PI3K-AKT- mammalian target of rapamycin (mTOR) pathway. Treatment with sirolimus, an mTOR inhibitor, may therefore be of benefit in patients with CLOVES syndrome. OBJECTIVE: Here we describe the efficacy and toxicity of sirolimus in a pediatric patient with progressive CLOVES syndrome. RESULTS: The child presented with a large and painful abdominal malformation, massive overgrowth of his feet, limb length discrepancy and genu valgum. There was dramatic clinical and radiographic improvement in the size and comfort of his abdominal mass within several months of initiating medical therapy. This, combined with orthopaedic care of his genu valgum, leg length discrepancy, and overgrowth of his feet, has allowed for significant functional gains. CONCLUSIONS: Multidisciplinary care is essential for comfort and functional gains in patients with CLOVES syndrome, particularly those with severe symptoms. Close monitoring while on sirolimus medical therapy combined with frequent reassessment of orthopedic needs can dramatically improve patient quality of life and outcomes.

Anesthesia in Carvajal syndrome; the first case report

2020 ◽  
Vol 24 (1) ◽  
pp. 105-107
Author(s):  
Sedighe Shahhosseini ◽  
Reza Aminnejad ◽  
Amir Shafa ◽  
Mehrdad Memarzade
Keyword(s):  
Intensive Care ◽  
Case Report ◽  
Surgical Resection ◽  
Genetic Disorder ◽  
Anesthetic Technique ◽  
Close Monitoring ◽  
Anesthesia Management ◽  
Rare Genetic Disorder ◽  
First Case ◽  
Anesthetic Considerations

Carvajal syndrome is a rare genetic disorder. Patients reporting for surgery pose some difficulties in anesthesia management. In this case report we present the case of a 12-year-old boy, who was a known case of Carvajal syndrome, referred for surgical resection of perianal condyloma. Close monitoring of hemodynamic status is the mainstay of anesthetic considerations in such patients. As in any other challenging scenario, it should be kept in mind that ‘there is no safest anesthetic agent, nor the safest anesthetic technique; there is only the safest anesthesiologist’. Citation: Shahhosseini S, Aminnejad R, Shafa A, Memarzadeh M. Anesthesia in Carvajal syndrome; the first case report. Anaesth pain intensive care 2020;24(1):___ DOI: https://doi.org/10.35975/apic.v24i1.

Description of a multidisciplinary model of care in a French cohort of adult patients with tuberous sclerosis complex

2020 ◽  
Vol 58 (1) ◽  
pp. 25-31
Author(s):  
Pierre Pfirmann ◽  
Jerome Aupy ◽  
Eva Jambon ◽  
Laetitia Idier ◽  
Mathilde Prezelin-Reydit ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Multidisciplinary Approach ◽  
Genetic Disorder ◽  
Multidisciplinary Care ◽  
Adult Patients ◽  
Bone Lesions ◽  
Interdisciplinary Management ◽  
Cutaneous Lesions ◽  
High Level

BackgroundTuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended by consensus guidelines.ObjectivesOur study aimed to give a complete description of our TSC adult cohort and to evaluate the multidisciplinary and interdisciplinary management model.MethodsData on each adult patient diagnosed with TSC, including disease manifestations, interventions and outcomes, were collected at baseline and updated annually. A multidisciplinary TSC approach with all the recommended explorations was carried out annually.Results90 patients were enrolled in Centre Hospitalier Universitaire de Bordeaux, between January 2000 and September 2018. Median age of patients at inclusion was 37 years (range, 27–47) and 20 years old at diagnosis of TSC. Regarding the occurrence of TSC manifestations, 97% of the patients had cutaneous lesions, 89% had neurological manifestations, 83% had renal manifestations and 100% had dental lesions with pits. More than half the patients had sclerotic bone lesions (68%), TSC-associated neuropsychiatric disorders (64%) and lymphangioleiomyomatosis (59%). A TSC multidisciplinary approach was developed including a global follow-up and an evaluation of TSC targeting organs, according to the recommendations. A satisfaction survey revealed global and entire satisfaction of patients with TSC.ConclusionWe obtained an accurate description of a cohort of adult patients with TSC. Our multidisciplinary approach model allowed us to provide optimal management of patients with TSC with a high level of patient satisfaction.

Reductive Otoplasty and Facial Debulking in a Pediatric Patient With PIK3CA-Related Overgrowth

FACE ◽  
2021 ◽  
pp. 273250162110482
Author(s):  
Rishub K. Das ◽  
Barry G. Rahman ◽  
James D. Phillips ◽  
Alexandra J. Borst ◽  
Nolan Jaeger ◽  
...  
Keyword(s):  
Pediatric Patient ◽  
Vascular Malformations ◽  
Genetic Diseases ◽  
Facial Soft Tissue ◽  
Novel Approach ◽  
Rare Genetic Diseases ◽  
Increased Risk ◽  
Surgical Debulking ◽  
Segmental Overgrowth ◽  
Overgrowth Syndromes

Overgrowth syndromes encompass a number of rare genetic diseases with heterogeneous clinical phenotypes. Accordingly, there is a strong imperative to collect data and classify these disorders to aid in diagnosis and management. Recent advances in the genetics of overgrowth syndromes have identified mutations in the PIK3CA gene. These somatic mutations manifest in progressive segmental overgrowth of fibrous and adipose tissue and bone, vascular malformations, and in some cases, increased risk for malignancy. Targeted medical therapy is under investigation for the management of PROS, but treatment of overgrowth relies on surgical debulking. Macrotia in PIK3CA-related overgrowth spectrum (PROS) has not been reported in the literature. In this case, we discuss a novel approach to reductive otoplasty and facial soft tissue debulking in a pediatric patient with PROS.

Biochemical features of primary cells from a pediatric patient with a gain-of-function ODC1 genetic mutation

2019 ◽  
Vol 476 (14) ◽  
pp. 2047-2057
Author(s):  
Chad R. Schultz ◽  
Caleb P. Bupp ◽  
Surender Rajasekaran ◽  
André S. Bachmann
Keyword(s):  
Pediatric Patient ◽  
De Novo ◽  
Genetic Disorder ◽  
Genetic Mutation ◽  
Dermal Fibroblasts ◽  
The Body ◽  
De Novo Mutation ◽  
Global Developmental Delay ◽  
Gain Of Function ◽  
Protein Variant

Abstract We recently described a new autosomal dominant genetic disorder in a pediatric patient caused by a heterozygous de novo mutation in the ornithine decarboxylase 1 (ODC1) gene. The new genetic disorder is characterized by global developmental delay, alopecia, overgrowth, and dysmorphic features. We hypothesized that this new mutation (c.1342 A>T) leads to a C-terminal truncation variant of the ODC protein that is resistant to normal proteasomal degradation, leading to putrescine accumulation in cells. ODC (E.C. 4.1.1.17) is a rate-limiting enzyme in the biosynthesis of polyamines (putrescine, spermidine, and spermine) that plays a crucial role during embryogenesis, organogenesis, and tumorigenesis. In this study, we show that primary dermal fibroblasts derived from a skin biopsy of a 3-year-old patient contain large amounts of ODC protein and putrescine compared with primary dermal (neonatal and adult) fibroblast control cells. Importantly, the accumulated ODC protein variant remained functionally active as we detected exceptionally high ODC enzyme activity in both primary dermal fibroblasts (12–17-fold of controls) and red blood cells (RBCs) (125–137-fold of controls), using a specific 14C radioactive ODC activity assay. Exposure of primary dermal fibroblasts to ODC inhibitor α-difluoromethylornithine (DFMO) reduced the ODC activity and putrescine to levels observed in controls without adversely affecting cell morphology or inducing cell death. In conclusion, our patient and potentially other patients that carry a similar ODC1 gain-of-function mutation might benefit from treatment with DFMO, a drug with a good safety profile, to suppress the exceptionally high ODC activity and putrescine levels in the body.

Vascular birthmarks

VASA ◽  
2008 ◽  
Vol 37 (1) ◽  
pp. 5-17 ◽  
Author(s):  
Willenberg ◽  
Baumgartner
Keyword(s):  
Vascular Malformations ◽  
Treatment Strategies ◽  
Multidisciplinary Care ◽  
High Flow ◽  
Low Flow ◽  
Management Options ◽  
Benign Neglect ◽  
Current Availability ◽  
History Of ◽  
Vascular Birthmarks

Vascular birthmarks can be classified into hemangioma and vascular malformations. Hemangioma are frequent tumours of early infancy demonstrating endothelial hyperplasia, a history of rapid neonatal growth and slow involution during later childhood. Treatment of hemangioma is dependent of stage and type of the lesion. Given the current availability of drugs, lasers, and other techniques to treat hemangioma safely, philosophy of "benign neglect" should not be considered anymore. Vascular malformations show a normal endothelial turnover, being present at birth and growing commensurately with the child. Exact diagnosis by employing modern diagnostic means, which are able to differentiate low-flow from high flow lesions is important for further therapeutic management. Beside conservative treatment strategies, use of laser, sclerotherapy, interventional embolization and surgical treatment are possible management options. Patients should receive multidisciplinary care in qualified vascular centres.

Infection of arachnoid cyst associated with vasospasm and stroke in a pediatric patient: case report

2020 ◽  
Vol 26 (5) ◽  
pp. 594-598
Author(s):  
Jenna R. Gale ◽  
Kamil W. Nowicki ◽  
Rachel M. Wolfe ◽  
Roberta K. Sefcik ◽  
Taylor J. Abel
Keyword(s):  
Pediatric Patient ◽  
Arachnoid Cyst ◽  
Internal Carotid ◽  
Pediatric Population ◽  
Arachnoid Cysts ◽  
Left Middle Cerebral Artery ◽  
Close Monitoring ◽  
Patient Case ◽  
Left Middle ◽  
Middle Cerebral Artery Infarct

Arachnoid cysts are relatively common and benign intraarachnoid membrane outpouchings containing CSF-like fluid. The majority of arachnoid cysts remain stable and asymptomatic and do not require intervention in the pediatric population. Here, the authors present the first reported case of an infected arachnoid cyst in a pediatric patient resulting in severe vasospasm of the left terminal internal carotid artery, left A1 segment, and left M1 branches with a left middle cerebral artery infarct. Their experience suggests that close monitoring is warranted for this condition and that the pediatric population may be at higher risk for vasospasm.

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