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Acrofacial dysostosis in a patient with the TSC2-PKD1 contiguous gene syndrome
  1. J G Dauwerse1,
  2. K Bouman2,
  3. A J van Essen2,
  4. A H van der Hout2,
  5. G Kolsters3,
  6. M H Breuning1,
  7. D J M Peters1
  1. 1Department of Human and Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
  2. 2Department of Clinical Genetics, University Hospital, Groningen, The Netherland
  3. 3Isala Clinics De Weezenlanden, Zwolle, The Netherlands
  1. Correspondence to:
 Dr D J M Peters, Department of Human and Clinical Genetics, Leiden University Medical Centre, Sylvius Laboratory, Wassenaarseweg 72, 2333AL Leiden, The Netherlands;
 d.j.m.peters{at}lumc.nl

https://doi.org/10.1136/jmg.39.2.136

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    The acrofacial dysostoses (AFD) are a heterogeneous group of disorders characterised by defects in craniofacial and limb development. The hallmarks include downward slanting palpebral fissures, malar hypoplasia, and receding chin (retrognathia) combined with variable limb malformations. The predominantly preaxial form is called Nager AFD and the predominantly postaxial form is called Genée-Wiedeman or Miller syndrome.1 A translocation t(X;9) suggests the localisation of a gene for Nager AFD on chromosome 9q32.2 More distally, on 9q34, one of the two major genes for tuberous sclerosis (TSC1) is located. Tuberous sclerosis (TSC) is an autosomal dominant trait with variable expression most frequently characterised by neurological impairment (seizures and learning difficulties), by dermatological manifestations (facial angiofibromas, periungual fibromas, shagreen patches, and hypopigmented macules), and by renal manifestations including angiomyolipomas and cystic disease.3

    The second gene for TSC, TSC2, maps to chromosome 16p13.3 tail to tail with the major gene for autosomal dominant polycystic kidney disease (ADPKD), the PKD1 gene. These genes are separated by 63 bp.4 The main symptom of ADPKD is the occurrence of a large number of fluid filled cysts in the kidneys. Cysts can in general be detected by ultrasonography or CT scanning around the second or third decade of life and end stage renal failure occurs at a mean age of 53 years in PKD1 patients.5 ADPKD is a systemic disorder with possible extrarenal manifestations such as cysts in other organs (particularly the liver), hypertension, cardiac valve abnormalities, and cerebral aneurysms. Features of TSC and ADPKD have been observed in patients with a TSC2-PKD1 contiguous gene syndrome. In these patients, a large portion of the adjacent TSC2 and PKD1 genes has been deleted on one chromosome. In a study by Sampson et al,6 17 of 22 patients with such a deletion were …

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