Atypical hematologic and renal manifestations in neurofibromatosis type I: coincidence or pathophysiological link?
European Journal of Medical Genetics. 2014-11-01; 57(11-12): 639-642
DOI: 10.1016/j.ejmg.2014.09.001
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1. Eur J Med Genet. 2014 Nov-Dec;57(11-12):639-42. doi: 10.1016/j.ejmg.2014.09.001.
Epub 2014 Sep 16.
Atypical hematologic and renal manifestations in neurofibromatosis type I:
coincidence or pathophysiological link?
Van-Gils J(1), Harambat J(2), Jubert C(3), Vidaud D(4), Llanas B(2), Perel Y(3),
Lacombe D(5), Goizet C(5).
Author information:
(1)CHU Bordeaux, Hôpital Pellegrin, Service de Génétique Médicale, Centre de
Référence des Anomalies du Développement Embryonnaire, 33076 Bordeaux Cedex,
France. Electronic address: .
(2)CHU Bordeaux, Hôpital Pellegrin-Enfants, Centre de référence maladies rénales
rares du Sud-Ouest (SORARE), Service de Pédiatrie, 33076 Bordeaux Cedex, France.
(3)CHU Bordeaux, Hôpital Pellegrin-Enfants, Unité d’Hématologie Oncologie
Pédiatrique, 33076 Bordeaux Cedex, France.
(4)Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Service de biochimie et
génétique moléculaire, 75679 Paris Cedex 14, France.
(5)CHU Bordeaux, Hôpital Pellegrin, Service de Génétique Médicale, Centre de
Référence des Anomalies du Développement Embryonnaire, 33076 Bordeaux Cedex,
France; Université Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme
(MRGM), EA4576, 33076 Bordeaux Cedex, France.
Neurofibromatosis type 1 (NF1) is an autosomal dominant, multi-system,
neurocutaneous disorder that predisposes to the development of benign and
malignant tumors with a birth incidence rate of 1 in 2500-3000. 50% of cases are
sporadic. The diagnosis is exclusively based on clinical assessment with clinical
diagnostic criteria such as café-au-lait spots, neurofibromas, axillary or groin
freckling, Lisch nodules, optic pathway glioma, bony dysplasia and first-degree
relative with NF1. We report a family with NF1 in which two members presented
atypical clinical features in addition to the classical diagnostic criteria.
Three relatives affected by NF1, a father and two of his three sons, are
described. The clinical diagnosis was originally worn in all three cases, with
the association many spots café-au -lait over the entire body and some axillary
freckling as well as first-degree relative. One case presented an Acute Myeloid
Leukemia (AML) type 2 at 10 years of age diagnosed before the revelation of
bicytopenia associated pallor and isolated asthenia. A second case presented a
nephrotic syndrome at 4 years of age due to the association of hydrops with
headache and asthenia. Direct sequencing of NF1 led to identify the familial
mutation, a previously unreported heterozygous missense mutation c.3443C > A,
p.Ala1148Glu in exon 20 which segregated with all three affected patients. The
family described in this report confirms the high clinical variability of NF1,
even intrafamilial, and raises the question as to whether rare features such as
AML and nephrotic syndrome are associated with NF1. Some NF1 patients presenting
glomerular diseases or AML have rarely been reported, but due to the small number
of cases described the mechanisms underlying these associations are poorly
understood. However, it seems important to be aware of the possible occurrence of
nephritic syndrome and/or malignant blood diseases in NF1 patients.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
DOI: 10.1016/j.ejmg.2014.09.001
PMID: 25234363 [Indexed for MEDLINE]