Overgrowth syndromes — clinical and molecular aspects and tumour risk

Brioude, Frédéric; Toutain, Annick; Giabicani, Éloïse; Cottereau, Edouard; Cormier‐Daire, Valérie; Netchine, Irène

doi:10.1038/s41574-019-0180-z

Cited by 77 publications

(65 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although almost all patients with CLOVES syndrome are intellectually normal, one report by Alomari showed that neurologic impairment was observed in around 50% of the study cohort [12]. Thorough details of overgrowth syndromes, generally, and PROS, specifically, are reviewed in the literature [6,13]. Table 1 displays the major clinical features of PROS [6].…”

Section: Discussionmentioning

confidence: 99%

CLOVES Syndrome in a Nine-month-old Infant

Alomar

Khedr

Alajlan

2019

Cureus

View full text Add to dashboard Cite

CLOVES syndrome is a recently described overgrowth syndrome. Clinically, it is characterized by congenital lipomatous overgrowth (CLO), vascular anomalies (V), epidermal nevi (E), and skeletal deformities (S). Genetically, it is characterized by a somatic gain-of-function mutation of the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. This somatic mutation is, in turn, associated with the activation of the protein kinase Bmammalian target of the rapamycin (AKT-mTOR) pathway that drives various signaling cascades. The end result is eventually promoting cell proliferation, growth, and survival. CLOVES syndrome is exceedingly uncommon, with less than 200 cases currently documented. Herein, we describe a case of CLOVES syndrome in a nine-month-old male infant who was referred to our dermatology clinic for further assessment and management. The diagnosis was made based on clinical findings and confirmed by genetic testing.

show abstract

Section: Discussionmentioning

confidence: 99%

CLOVES Syndrome in a Nine-month-old Infant

Alomar

Khedr

Alajlan

2019

Cureus

View full text Add to dashboard Cite

show abstract

“…This subgroup shows different cancer types: hepatoblastoma, rhabdomyosarcoma, and gonadoblastoma but not in Wilms tumor. Patients with H19/IGF2:IG-DMR hypermethylated present Wilms tumor and hepatoblastoma their recurrence is related to IGF2 overexpression during cancer development ( Akmal et al, 1995 ; Rump et al, 2005 ; Maas et al, 2016 ; Mussa et al, 2017 ; Brioude et al, 2019 ). Several studies observing different cohorts of BWS patients confirmed higher tumor risk associated with the H19/IGF2:IG-DMR hypermethylated and UPD(11)pat subgroup and high frequency for Wilms tumor and hepatoblastoma ( Maas et al, 2016 ; Ounap, 2016 ; Brioude et al, 2018 ; Kamien et al, 2018 ; MacFarland et al, 2018 ; Wang et al, 2020 ).…”

Section: Predisposition In Tumor Development: Estimated Cancer Risk Imentioning

confidence: 99%

Preclinical and Clinical Epigenetic-Based Reconsideration of Beckwith-Wiedemann Syndrome

et al. 2020

View full text Add to dashboard Cite

Epigenetics has achieved a profound impact in the biomedical field, providing new experimental opportunities and innovative therapeutic strategies to face a plethora of diseases. In the rare diseases scenario , Beckwith-Wiedemann syndrome (BWS) is a pediatric pathological condition characterized by a complex molecular basis, showing alterations in the expression of different growth-regulating genes. The molecular origin of BWS is associated with impairments in the genomic imprinting of two domains at the 11p15.5 chromosomal region. The first domain contains three different regions: insulin growth like factor gene ( IGF2 ), H19 , and abnormally methylated DMR1 region. The second domain consists of cell proliferation and regulating-genes such as CDKN1C gene encoding for cyclin kinase inhibitor its role is to block cell proliferation. Although most cases are sporadic, about 5–10% of BWS patients have inheritance characteristics. In the 11p15.5 region, some of the patients have maternal chromosomal rearrangements while others have Uniparental Paternal Disomy UPD(11)pat. Defects in DNA methylation cause alteration of genes and the genomic structure equilibrium leading uncontrolled cell proliferation, which is a typical tumorigenesis event. Indeed, in BWS patients an increased childhood tumor predisposition is observed. Here, we summarize the latest knowledge on BWS and focus on the impact of epigenetic alterations to an increased cancer risk development and to metabolic disorders. Moreover, we highlight the correlation between assisted reproductive technologies and this rare disease. We also discuss intriguing aspects of BWS in twinning. Epigenetic therapies in clinical trials have already demonstrated effectiveness in oncological and non-oncological diseases. In this review, we propose a potential “epigenetic-based” approaches may unveil new therapeutic options for BWS patients. Although the complexity of the syndrome is high, patients can be able to lead a normal life but tumor predispositions might impair life expectancy. In this sense epigenetic therapies should have a supporting role in order to guarantee a good prognosis.

show abstract

“…In patients affected, generalized or segmental overgrowth can be observed sometimes. This is accompanied by visceromegaly, macrocephaly, or neurological symptoms like autism and learning deficits [17]. There is some overlap between overgrowth syndromes and mTORopathies.…”

Section: Clinical Development Of Pi3k and Mtor Inhibitors In Non-omentioning

confidence: 99%

“…In recent years, sequencing efforts have linked rare genetic disorders like Tuberous Sclerosis Complex (TSC) to hyperactivated PI3K/mTOR signaling. Germline mutations or mosaic mutations of different genes were found in tissue of versatile functions, e.g., in skin, kidney, or brain [15,16,17]. Mutated proteins found in genetic disorders are depicted in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

PI3K/mTOR Pathway Inhibition: Opportunities in Oncology and Rare Genetic Diseases

Hillmann

Fabbro

2019

IJMS

View full text Add to dashboard Cite

The phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway has been implicated as a cancer target. Big pharma players and small companies have been developing small molecule inhibitors of PI3K and/or mTOR since the 1990s. Although four inhibitors have been approved, many open questions regarding tolerability, patient selection, sensitivity markers, development of resistances, and toxicological challenges still need to be addressed. Besides clear oncological indications, PI3K and mTOR inhibitors have been suggested for treating a plethora of different diseases. In particular, genetically induced PI3K/mTOR pathway activation causes rare disorders, known as overgrowth syndromes, like PTEN (phosphatase and tensin homolog) hamartomas, tuberous sclerosis complex (TSC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS), and activated PI3-Kinase delta syndrome (PI3KCD, APDS). Some of those disorders likeTSC or hemimegalencephaly, which are one of the PROS disorders, also belong to a group of diseases called mTORopathies. This group of syndromes presents with additional neurological manifestations associated with epilepsy and other neuropsychiatric symptoms induced by neuronal mTOR pathway hyperactivation. While PI3K and mTOR inhibitors have been and still are intensively tested in oncology indications, their use in genetically defined syndromes and mTORopathies appear to be promising avenues for a pharmacological intervention.

show abstract

Overgrowth syndromes — clinical and molecular aspects and tumour risk

Cited by 77 publications

References 126 publications

CLOVES Syndrome in a Nine-month-old Infant

CLOVES Syndrome in a Nine-month-old Infant

Preclinical and Clinical Epigenetic-Based Reconsideration of Beckwith-Wiedemann Syndrome

PI3K/mTOR Pathway Inhibition: Opportunities in Oncology and Rare Genetic Diseases

Contact Info

Product

Resources

About