The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management

Tan, Wen‐Hann; Baris, Hagit N.; Burrows, Patricia E.; Robson, Caroline D.; Alomari, Ahmad I.; Mulliken, John B.; Fishman, Steven J.; Irons, Mira

doi:10.1136/jmg.2007.048934

Cited by 248 publications

(162 citation statements)

References 29 publications

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“…Then Herman et al 45 and Buxbaum et al 86 reported individuals with macrocephaly and autism associated with mutations in the PTEN gene. Tan et al 87 reported that most children with PTEN mutations are macrocephalic. Among individuals with autism, those with PTEN mutations can be differentiated from those without PTEN mutations by the presence of severe to extreme macrocephaly (head circumferences >+3SD) in the former.…”

Section: Pten Genementioning

confidence: 99%

Genetic causes of syndromic and non‐syndromic autism

Çağlayan

2010

Develop Med Child Neuro

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Aims Over the past decade, genetic tests have become available for numerous heritable disorders, especially those whose inheritance follows the Mendelian model. Autism spectrum disorders (ASDs) represent a group of developmental disorders with a strong genetic basis. During the past few years, genetic research in ASDs has been successful in identifying several vulnerability loci and a few cytogenetic abnormalities or single‐base mutations implicated in the causation of autism. Method In this study the literature was reviewed to highlight genotype–phenotype correlations between causal gene mutations or cytogenetic abnormalities and behavioural or morphological phenotypes. Results Based on this knowledge, practical information is offered to help clinicians pursue targeted genetic testing of individuals with autism whose clinical phenotype is suggestive of a specific genetic or genomic aetiology. Interpretation Comprehensive research into the molecular mechanism of autism is required to aid the development of disease‐specific targeted therapies. In order to transfer this recently acquired knowledge into clinical practice, it is critical to define a set of phenotypic inclusion criteria that must be met by affected probands to justify their enrolment in a specific genetic testing programme.

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Section: Pten Genementioning

confidence: 99%

Genetic causes of syndromic and non‐syndromic autism

Çağlayan

2010

Develop Med Child Neuro

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“…A population-based study in Amsterdam including a review of the literature at that time cited a weighted prevalence of 21%, 2 whereas two other retrospective studies from tertiary referral centers found macrocephaly in 100% of patients studied. 9,10 In addition to PHTS, macrocephaly is a component of many other genetic syndromes, a few of which have had occipital-frontal circumference (OFC) norms ascertained and published. However, the systematic ascertainment and characterisation of head circumference has not been performed in CS or BRRS nor in the molecularly defined PHTS.…”

Section: Introductionmentioning

confidence: 99%

Analysis of prevalence and degree of macrocephaly in patients with germline PTEN mutations and of brain weight in Pten knock-in murine model

et al. 2011

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PTEN Hamartoma Tumour Syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), and other conditions resulting from germline mutation of the PTEN tumour suppressor gene. Although macrocephaly, presumably due to megencephaly, is found in both CS and BRRS, the prevalence and degree have not been formally assessed in PHTS. We evaluated head size in a prospective nested series of 181 patients found to have pathogenic germline PTEN mutations. Clinical data including occipital-frontal circumference (OFC) measurement were requested for all participants. Macrocephaly was present in 94% of 161 evaluable PHTS individuals. In patients r18 years, mean OFC was +4.89 standard deviations (SD) above the population mean with no difference between genders (P¼0.7). Among patients 418 years, average OFC was 60.0 cm in females and 62.8 cm in males (Po0.0001). To systematically determine whether macrocephaly was due to megencephaly, we examined Pten M3M4 missense mutant mice generated and maintained on mixed backgrounds. Mice were killed at various ages, brains were dissected out and weighed. Average brain weight for Pten M3M4 homozygous mice (N¼15) was 1.02 g compared with 0.57 g for heterozygous mice (N¼29) and 0.49 g for wild-type littermates (N¼24) (Po0.0001). Macrocephaly, secondary to megencephaly, is an important component of PHTS and more prevalent than previously appreciated. Patients with PHTS have increased risks for breast and thyroid cancers, and early diagnosis is key to initiating timely screening to reduce patient morbidity and mortality. Clinicians should consider germline PTEN testing at an early point in the diagnostic work-up for patients with extreme macrocephaly.

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“…Affected individuals are at risk for developing various benign and malignant tumors [1,2]. In addition, PTEN has been linked with vascular anomalies [2]. Given the extent of the tumor and the potential for substantial morbidity with surgical resection, surgical removal of the mass is currently deferred in this boy.…”

mentioning

confidence: 99%

“…Affected individuals are at risk for developing various benign and malignant tumors [1,2]. In addition, PTEN has been linked with vascular anomalies [2].…”

mentioning

confidence: 99%