A standard of care for individuals with <scp><i>PIK3CA</i></scp>‐related disorders: An international expert consensus statement

Douzgou, Sofia; Rawson, M.D.; Baselga, Eulàlia; Danielpour, Moise; Faivre, Laurence; Kashanian, Alon; Keppler‐Noreuil, Kim M.; Kuentz, Paul; Mancini, Grazia M.S.; Manière, Marie‐Cécile; Martínez‐Glez, Víctor; Parker, Victoria; Semple, Robert K.; Srivastava, Siddharth; Vabres, P.; Wit, Marie‐Claire Y. de; Graham, John M.; Clayton‐Smith, Jill; Mirzaa, Ghayda; Biesecker, Leslie G.

doi:10.1111/cge.14027

Cited by 26 publications

(27 citation statements)

References 62 publications

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“…Depression and anxiety are common, especially as patients get older. Risk of malignancy, although occurrences are rare [ 20 ], may contribute to ongoing anxiety and reduced quality of life. A panel discussion in which the authors discuss mental health and quality of life is provided in Additional file 6 .…”

Section: Resultsmentioning

confidence: 99%

Mapping the PIK3CA-related overgrowth spectrum (PROS) patient and caregiver journey using a patient-centered approach

Rodríguez‐Laguna

Davis²,

Finger³

et al. 2022

Orphanet J Rare Dis

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Background PROS disorders are driven by somatic, gain-of-function mutations in PIK3CA that result in hyperactivation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway. PROS encompasses a broad spectrum of overlapping phenotypes (including overgrowth and vascular malformations) that vary significantly in their severity; every case is unique, leading to different, complex experiences. Here, we aim to describe the PROS experience from the patients’ and caregivers’ points of view, from onset to diagnosis to treatment and support. Results The PROS patient journey was developed using a literature review, an ethnography study, health care professional (HCP) research, and social listening. It was then validated with patients, caregivers, and patient advocates. Physician research included 94 PROS centers and other vascular anomaly centers throughout the United States and Europe. Ethnographic research included 24 patients, caregivers, and/or advocates; selected data from 223 patients were reviewed. Key priority areas of need were identified, along with barriers to and potential enablers of quality care. Visual mapping of the PROS patient and family journey was developed to identify key personal health and system issues, and opportunities for improvements throughout patients’ lifespans. Maps were also developed for 3 specific conditions: Klippel–Trénaunay syndrome (K–T); congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal anomalies (CLOVES) syndrome; and megalencephaly-capillary malformation syndrome (M-CM). Overall, most patients with PROS conditions and their families struggle with a long path to diagnosis, access to genetic testing, and finding qualified specialists. Following diagnosis, patients and families are frequently challenged with major medical events, comorbidities, unpredictability, frequent hospitalization, impact on school and work, the need for multidisciplinary care, unwanted attention, adverse impact on mental and emotional health, and financial pressures. Lack of effective pain management emerged as a substantial issue. Challenges and barriers to quality care shift throughout patients’ lifespans; transition from pediatric to adult care can be especially difficult. Conclusions This patient journey in PROS was created in collaboration with patients, caregivers, and advocates as key partners. This novel methodology, which could be applied elsewhere, can more accurately identify areas of unmet need, barriers to care, education topics, and assist HCPs to understand the patient and family perspective.

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Section: Resultsmentioning

confidence: 99%

Mapping the PIK3CA-related overgrowth spectrum (PROS) patient and caregiver journey using a patient-centered approach

Rodríguez‐Laguna

Davis²,

Finger³

et al. 2022

Orphanet J Rare Dis

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“…They found that nonhotspot pathogenic variants were more frequent in the syndromic LM group (including CLOVES and unclassified PROS) compared to the common or combined LM group. Most recently, a consensus statement was posed defining two broad categories for patients with molecularly confirmed PROS, in order to guide the clinical management (Douzgou et al, 2021). Patients with activating mosaic PIK3CA variants, overgrowth, and/or vascular findings were classified based on whether they had megalencephaly and/or polymicrogyria (MCAP), or not (non‐MCAP PROS).…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and molecular characterization of five patients with PIK3CA‐related overgrowth spectrum (PROS)

İli

Taşdelen

Durmaz

et al. 2022

American J of Med Genetics Pt A

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Somatic and germline PI3K-AKT-mTOR pathway pathogenic variants are involved in several segmental overgrowth phenotypes such as the PIK3CA-related overgrowth spectrum (PROS), Proteus syndrome, and PTEN hamartoma tumor syndrome. In this study, we describe five patients with PROS. We identified by high-throughput sequencing four different somatic PIK3CA pathogenic variants in five individuals. The Glu726Lys variant, which was previously reported in megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, was identified in two patients with unclassified PROS. The Cys420Arg substitution, which was previously reported in CLOVES, was found in a patient with fibroadipose hyperplasia. Additionally, relatively rare pathogenic variants, His1047Tyr and Tyr1021Cys, were detected in two patients with MCAP. Therefore, we suggest performing deep sequencing of PIK3CA in all patients with suspected PROS, instead of targeted polymerase chain reaction for hotspot pathogenic variants.

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“…Patient 5 lacked Ito hypomelanosis which had been previously reported in another patient with overgrowth and Ito hypomelanosis, harboring the same genetic variant. Endocrinology issues are rarely reported in PROS patients, including hypoglycemia, growth hormone deficiency, or other forms of hypothalamic–pituitary dysfunction (Douzgou et al, 2022); however, to date no case of peripheral hypogonadism, as in Patient 2, is found in the literature.…”

Section: Discussionmentioning

confidence: 99%

“…For this reason, the authors recommend counseling the families on a case‐by‐case basis. Further longitudinal studies and clinical trials are necessary to provide precise management recommendations for these aspects (Douzgou et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic analysis of patients with segmental overgrowth features and somatic mammalian target of rapamycin (mTOR) pathway disruption: Possible novel clinical issues

Romano

Madia

Marco

et al. 2022

Birth Defects Research

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Segmental overgrowth syndromes include a group of clinical entities, all characterized by the abundant proliferation of tissues or organs in association with vascular abnormalities. These syndromes show a wide spectrum of severity ranging from limited involvement of only small areas of the body to complex cases with impressive distortions of multiple tissues and organs. It is now clear that somatic mutations in genes of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway (in brief “mTOR pathway”) are responsible for such entities. Not all the cells of the body carry the same causative mutation, which is mosaic, appearing from two (or more) distinct cell lineages after fertilization. In this article, we reconsider the clinical spectrum and surveillance programs of patients with segmental overgrowth syndromes, based on the features of six patients with diverse clinical forms of overgrowth and pathogenic variants in genes of the mTOR pathway.

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A standard of care for individuals with PIK3CA‐related disorders: An international expert consensus statement

Cited by 26 publications

References 62 publications

Mapping the PIK3CA-related overgrowth spectrum (PROS) patient and caregiver journey using a patient-centered approach

Mapping the PIK3CA-related overgrowth spectrum (PROS) patient and caregiver journey using a patient-centered approach

Phenotypic and molecular characterization of five patients with PIK3CA‐related overgrowth spectrum (PROS)

Clinical and genetic analysis of patients with segmental overgrowth features and somatic mammalian target of rapamycin (mTOR) pathway disruption: Possible novel clinical issues

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