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J Med Genet. 2010 Sep;47(9):623-30. doi: 10.1136/jmg.2009.075937. Epub 2010 Jun 12.

Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions.

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  • 1Department of Maxillofacial Surgery, University Medical Centre, Hamburg-Eppendorf, Germany.

Abstract

BACKGROUND:

Large deletions of the NF1 gene region occur in approximately 5% of patients with neurofibromatosis type-1 (NF1) and are associated with particularly severe manifestations of the disease. However, until now, the genotype-phenotype relationship has not been comprehensively studied in patients harbouring large NF1 gene deletions of comparable extent (giving rise to haploinsufficiency of the same genes).

METHOD:

We have performed the most comprehensive clinical/neuropsychological characterisation so far undertaken in NF1 deletion patients, involving 29 patients with precisely determined type-1 NF1 (1.4 Mb) deletions.

RESULTS:

Novel clinical features found to be associated with type-1 NF1 deletions included pes cavus (17% of patients), bone cysts (50%), attention deficit (73%), muscular hypotonia (45%) and speech difficulties (48%). Type-1 NF1 deletions were found to be disproportionately associated with facial dysmorphic features (90% of patients), tall stature (46%), large hands and feet (46%), scoliosis (43%), joint hyperflexibility (72%), delayed cognitive development and/or learning disabilities (93%) and mental retardation (IQ<70; 38%), as compared with the general NF1 patient population. Significantly increased frequencies (relative to the general NF1 population) of plexiform neurofibromas (76%), subcutaneous neurofibromas (76%), spinal neurofibromas (64%) and MPNSTs (21%) were also noted in the type-1 deletion patients. Further, 50% of the adult patients exhibited a very high burden of cutaneous neurofibromas (N>or=1000).

CONCLUSION:

These findings emphasise the importance of deletion analysis in NF1 since frequent monitoring of tumour presence and growth could potentiate early surgical intervention thereby improving patient survival.

PMID:
20543202
[PubMed - indexed for MEDLINE]
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