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J Med Genet 40:e50 doi:10.1136/jmg.40.4.e50
  • Online mutation report

Novel PHF6 mutation p.D333del causes Börjeson-Forssman-Lehmann syndrome

  1. A Baumstark1,
  2. K M Lower2,3,
  3. A Sinkus4,
  4. I Andriuškevičiūtė4,
  5. L Jurkėnienė4,
  6. J Gécz2,3,
  7. W Just1
  1. 1Abt Humangenetik, Universität Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany
  2. 2Neurogenetics Laboratory, Department of Laboratory Genetics, Women’s and Children’s Hospital, 72 King William Road, North Adelaide, SA 5006, Australia
  3. 3Department of Paediatrics, The University of Adelaide, Adelaide, Australia
  4. 4Laboratory of Cytogenetics, Department of Biology, Kaunas University of Medicine, Mickevičiaus 9, LT-3000 Kaunas, Lithuania
  1. Correspondence to:
 Dr W Just, Abt Humangenetik, Universitätsklinikum Ulm Albert-Einstein-Allee 11, 89081 Ulm, Germany; 
 walter.just{at}medizin.uni-ulm.de

    The X linked mental retardation group XLMR comprises at least 160 syndromic and non-syndromic disorders of the human X chromosome as summarised by the online catalogue of Mendelian inheritance in man (OMIM; accession date July 2002; http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM). For 113 of these, the gene locus has been mapped, although the gene itself may not have been identified yet.

    Börjeson-Forssman-Lehmann syndrome (BFLS)1 belongs to the syndromic forms of XLMR disorders.2 BFLS is best described as a mental deficiency-endocrine disorder. This relatively rare disorder was described for the first time in 1962.1 It is characterised by moderate to severe mental retardation, excessive facial fat, large ears, marked obesity, hypogonadism, and gynaecomastia. A detailed pathoanatomical follow up of the patient from the first publication of the syndrome completed the thorough description of the phenotype.3 Although BFLS is an X chromosomal recessively inherited disorder, it may also be seen in women,2,4 perhaps as a consequence of X inactivation skewing, as has been proven by methylation specific PCR.5 Subjects with BFLS may show intra- and interfamilial phenotypic variability.6 There are other autosomal and X linked disorders with similar symptoms, making the accurate diagnosis of BFLS more difficult. The differential diagnosis of obesity related syndromes includes syndromes like Prader-Willi, Bardet-Biedl, or Wilson-Turner syndromes. However, obesity as a cardinal symptom is not necessarily linked to these loci, as was proven by a linkage analysis of obese sibs.7 Therefore, a thorough analysis of the phenotype is essential. Some features, which are quite frequent in BFLS and allow for the discrimination of this disorder from other mental retardation/obesity related syndromes are: hypogonadism, long, large ears, prominent supraorbital ridge, long philtrum, protruding lips, kyphosis, coarse face, and narrow palpebral fissures, which have been described also as lid ptosis.8

    BFLS has been …