The clinical picture of the Börjeson-Forssman-Lehmann syndrome in males and heterozygous females with PHF6 mutations

G. Turner, K. M. Lower, S. M. White, M. Delatycki, A. K. Lampe, M. Wright, J. Clayton-Smith, B. Kerr, S. Schelley, H. E. Hoyme, B. B A De Vries, T. Kleefstra, Markus Grompe, B. Cox, J. Gecz, Michael Partington

Research output: Contribution to journalArticle

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Abstract

The usual description of the Börjeson-Forssman-Lehmann syndrome (BFLS) is that of a rare, X-linked, partially dominant condition with severe intellectual disability, epilepsy, microcephaly, coarse facial features, long ears, short stature, obesity, gynecomastia, tapering fingers, and shortened toes. Recently, mutations have been identified in the PHF6 gene in nine families with this syndrome. The clinical history and physical findings in the affected males reveal that the phenotype is milder and more variable than previously described and evolves with age. Generally, in the first year, the babies are floppy, with failure to thrive, big ears, and small external genitalia. As schoolboys, the picture is one of learning problems, moderate short stature, with emerging truncal obesity and gynecomastia. Head circumferences are usually normal, and macrocephaly may be seen. Big ears and small genitalia remain. The toes are short and fingers tapered and malleable. In late adolescence and adult life, the classically described heavy facial appearance emerges. Some heterozygous females show milder clinical features such as tapering fingers and shortened toes. Twenty percent have significant learning problems, and 95% have skewed X inactivation. We conclude that this syndrome may be underdiagnosed in males in their early years and missed altogether in isolated heterozygous females.

Original languageEnglish (US)
Pages (from-to)226-232
Number of pages7
JournalClinical Genetics
Volume65
Issue number3
DOIs
StatePublished - Mar 2004

Fingerprint

Toes
Fingers
Gynecomastia
Genitalia
Mutation
Ear
Obesity
Learning
Megalencephaly
External Ear
X Chromosome Inactivation
Failure to Thrive
Microcephaly
Intellectual Disability
Epilepsy
Head
Phenotype
Genes

Keywords

  • Big ears
  • Börjeson-Forssman-Lehmann syndrome
  • Gynecomastia
  • Hypotonia
  • PHF6 mutations
  • Skewed X inactivation
  • Syndromic X-linked mental retardation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Turner, G., Lower, K. M., White, S. M., Delatycki, M., Lampe, A. K., Wright, M., ... Partington, M. (2004). The clinical picture of the Börjeson-Forssman-Lehmann syndrome in males and heterozygous females with PHF6 mutations. Clinical Genetics, 65(3), 226-232. https://doi.org/10.1111/j.0009-9163.2004.00215.x

The clinical picture of the Börjeson-Forssman-Lehmann syndrome in males and heterozygous females with PHF6 mutations. / Turner, G.; Lower, K. M.; White, S. M.; Delatycki, M.; Lampe, A. K.; Wright, M.; Clayton-Smith, J.; Kerr, B.; Schelley, S.; Hoyme, H. E.; De Vries, B. B A; Kleefstra, T.; Grompe, Markus; Cox, B.; Gecz, J.; Partington, Michael.

In: Clinical Genetics, Vol. 65, No. 3, 03.2004, p. 226-232.

Research output: Contribution to journalArticle

Turner, G, Lower, KM, White, SM, Delatycki, M, Lampe, AK, Wright, M, Clayton-Smith, J, Kerr, B, Schelley, S, Hoyme, HE, De Vries, BBA, Kleefstra, T, Grompe, M, Cox, B, Gecz, J & Partington, M 2004, 'The clinical picture of the Börjeson-Forssman-Lehmann syndrome in males and heterozygous females with PHF6 mutations', Clinical Genetics, vol. 65, no. 3, pp. 226-232. https://doi.org/10.1111/j.0009-9163.2004.00215.x
Turner, G. ; Lower, K. M. ; White, S. M. ; Delatycki, M. ; Lampe, A. K. ; Wright, M. ; Clayton-Smith, J. ; Kerr, B. ; Schelley, S. ; Hoyme, H. E. ; De Vries, B. B A ; Kleefstra, T. ; Grompe, Markus ; Cox, B. ; Gecz, J. ; Partington, Michael. / The clinical picture of the Börjeson-Forssman-Lehmann syndrome in males and heterozygous females with PHF6 mutations. In: Clinical Genetics. 2004 ; Vol. 65, No. 3. pp. 226-232.
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AU - Lampe, A. K.

AU - Wright, M.

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AU - De Vries, B. B A

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