Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants

Tian, Wen; Huang, Yingzhao; Sun, Li‐Ying; Guo, Yang; Zhao, Sen; Lin, Mao; Dong, Xian‐Zhe; Zhong, Wenyao; Yin, Yuehan; Chen, Zefu; Zhang, Nan; Zhang, Yuanqiang; Wang, Lianlei; Lin, Jiachen; Yan, Zihui; Yang, Xinzhuang; Zhao, Jianfeng; Qiu, Guixing; Zhang, Jianguo; Wu, Zhihong; Wu, Nan

doi:10.1186/s13023-020-01572-9

Cited by 17 publications

(15 citation statements)

References 30 publications

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“…Most of these disorganized overgrowths of essentially mesenchymal elements have been more recently termed PTEN hamartoma of soft tissue (PHOST) [178]. In rare cases of Cowden and Cowdenlike syndromes as well as in proteus syndrome, other susceptibility genes have been reported (see below) [179][180][181][182].…”

Section: Pten Hamartoma Tumor Syndromes (Pths)mentioning

confidence: 99%

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

et al. 2021

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Cancer derived from thyroid follicular epithelial cells is common; it represents the most common endocrine malignancy. The molecular features of sporadic tumors have been clarified in the past decade. However the incidence of familial disease has not been emphasized and is often overlooked in routine practice. A careful clinical documentation of family history or familial syndromes that can be associated with thyroid disease can help identify germline susceptibility-driven thyroid neoplasia. In this review, we summarize a large body of information about both syndromic and non-syndromic familial thyroid carcinomas. A significant number of patients with inherited non-medullary thyroid carcinomas manifest disease that appears to be sporadic disease even in some syndromic cases. The cytomorphology of the tumor(s), molecular immunohistochemistry, the findings in the non-tumorous thyroid parenchyma and other associated lesions may provide insight into the underlying syndromic disorder. However, the increasing evidence of familial predisposition to non-syndromic thyroid cancers is raising questions about the importance of genetics and epigenetics. What appears to be “sporadic” is becoming less often truly so and more often an opportunity to identify and understand novel genetic variants that underlie tumorigenesis. Pathologists must be aware of the unusual morphologic features that should prompt germline screening. Therefore, recognition of harbingers of specific germline susceptibility syndromes can assist in providing information to facilitate early detection to prevent aggressive disease.

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Section: Pten Hamartoma Tumor Syndromes (Pths)mentioning

confidence: 99%

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

et al. 2021

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“…5 The aetiology of macrodactyly is not well understood, however, its association with PIK3CA /AKT1 genes has been reported in 24 patients mosaic for this variant. 6,7 In this case study, we reported a rare congenital macrodactyly of second and third toe of right foot along with deformed leg in 16-year-old girl.…”

Section: Introductionmentioning

confidence: 81%

An experience with Foot Macrodactyly: A case report and review of literature

Kaur

Kaur²

2022

IJOR

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Macrodactyly is a rare congenital malformation with clinical manifestations such as enlargement of soft tissue and osseous elements. It causes various health issues such as pain, difficulty in wearing shoes, impairment in ambulatory ability and gait development, aesthetic problem, and psychological issues. The aetiology of macrodactyly is ambiguous; however, its association with PIK3CA /AKT1 genes has been reported recently. In the present study, a rare congenital macrodactyly of second and third toe of right foot along with deformed leg in 16-year-old girl has been reported. A progressive increase in the size of the second and third toe of the right foot and deformed reddish swollen area on the same lower leg below knee was seen in the patient. The malformation was present at the time of birth and at the age of one year the patient was operated for macrodactyly, but again the toe progressively increased to the previous size. She was presented with multiple health problems. There was no positive family history and/or other congenital malformation. Thus, it was suggested that due to variable phenotypic manifestations, appropriate treatment should be chosen for the patient individually.

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“…We included ten families diagnosed with CCA and carrying pathogenic FBN2 variant from Beijing Jishuitan Hospital and Peking Union Medical College Hospital based on the D eciphering disorders I nvolving S coliosis and CO morbidities (DISCO) study ( http://www.discostudy.org/ ) ( Tian et al, 2020 ; Sun et al, 2021 ). Informed consent was obtained from all patients or their guardians.…”

Section: Methodsmentioning

confidence: 99%

Identification of Novel FBN2 Variants in a Cohort of Congenital Contractural Arachnodactyly

et al. 2022

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Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder of connective tissue characterized by crumpled ears, arachnodactyly, camptodactyly, large joint contracture, and kyphoscoliosis. The nature course of CCA has not been well-described. We aim to decipher the genetic and phenotypic spectrum of CCA. The cohort was enrolled in Beijing Jishuitan Hospital and Peking Union Medical College Hospital, Beijing, China, based on Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study (http://www.discostudy.org/). Exome sequencing was performed on patients’ blood DNA. A recent published CCA scoring system was validated in our cohort. Seven novel variants and three previously reported FBN2 variants were identified through exome sequencing. Two variants outside of the neonatal region of FBN2 gene were found. The phenotypes were comparable between patients in our cohort and previous literature, with arachnodactyly, camptodactyly and large joints contractures found in almost all patients. All patients eligible for analysis were successfully classified into likely CCA based on the CCA scoring system. Furthermore, we found a double disease-causing heterozygous variant of FBN2 and ANKRD11 in a patient with blended phenotypes consisting of CCA and KBG syndrome. The identification of seven novel variants broadens the mutational and phenotypic spectrum of CCA and may provide implications for genetic counseling and clinical management.

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Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants

Cited by 17 publications

References 30 publications

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

An experience with Foot Macrodactyly: A case report and review of literature

Identification of Novel FBN2 Variants in a Cohort of Congenital Contractural Arachnodactyly

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