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PTEN hamartoma tumour syndrome: variability of an entity
  1. J H M Merks1,
  2. L S de Vries2,
  3. X-P Zhou5,
  4. P Nikkels3,
  5. P G Barth4,
  6. C Eng5,
  7. R C M Hennekam6
  1. 1Department of Paediatric Oncology, Emma Children’s Hospital, Academic Medical Centre, Amsterdam, The Netherlands
  2. 2Department of Neonatology Wilhelmina Children’s Hospital, Utrecht Medical Centre, the Netherlands
  3. 3Department of Pathology, Wilhelmina Children’s Hospital, Utrecht Medical Centre, The Netherlands
  4. 4Department of Paediatric Neurology, Emma Children’s Hospital, Academic Medical Centre, Amsterdam, The Netherlands
  5. 5Clinical Cancer Genetics Program and Human Cancer Genetics Program, Comprehensive Cancer Centre, Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA
  6. 6Department of Paediatrics and Institute for Human Genetics, Emma Children’s Hospital, Academic Medical Centre, Amsterdam, The Netherlands
  1. Correspondence to:
 Dr Hans Merks
 Department of Paediatric Oncology, Floor F8-Room 245, Emma Children’s Hospital-Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; j.h.merksamc.uva.nl

https://doi.org/10.1136/jmg.40.10.e111

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    Cowden syndrome (CS; OMIM 158350) is an autosomal dominant disorder with age related penetrance characterised by mucocutaneous lesions, macrocephaly and an increased risk of cancer, especially of the breast, thyroid and endometrium.1,2 The phenotype in CS has proven to be highly variable, which became especially evident after identification of the susceptibility gene PTEN.3,4 This is also shown in the change in incidence figures, which were found to be at least five times higher after PTEN was identified (estimated incidence before PTEN identification 1:1 000 000,5 and after >1:200 000.6,7). Bannayan-Riley-Ruvalcaba syndrome (BRRS; OMIM 153480) is allelic to CS and is characterised by the triad of macrocephaly, lipomas, and pigmented macules of the glans penis.8 Proteus syndrome (PS; OMIM 176920) is a disorder characterised by overgrowth of hands and/or feet, asymmetry of limbs, connective tissue, and epidermal naevi, vascular and lymphatic malformations, and cranial hyperostosis.8 Proteus-like syndrome (PLS) is another closely related disorder, where individuals are characterised by the presence of macrocephaly, lipomas and overgrowth not meeting the criteria for CS, BRRS, or PS.8 Germline PTEN mutations have been found in 80% of individuals with CS, 60% of individuals with BRRS, up to 20% with PS, and 50% with PLS.9,10

    Here, we present a family (a mother and three sons) in which phenotype was extremely variable, one member having macrocephaly, normal intelligence, and minimal pigmentation abnormalities; another member with macrocephaly with developmental delay; another with macrocephaly, delay and lipoma; and the last member having hemimegalencephaly (HME), Jadassohn naevus sebaceous, and neonatal demise. All were found to have the same germline mutation in PTEN.

    CASE REPORTS

    Case 1

    The proband was the thirdborn child of non-consanguineous parents. His two older sisters were healthy. Prenatal routine sonography showed a unilateral ventricular dilatation. He …

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