Myeloproliferative disorder in Noonan syndrome.
Children with Noonan syndrome (NS) are at increased risk of developing juvenile myelomonocytic leukemia (JMML) or a myeloproliferative disorder associated with NS (MPD/NS) resembling JMML in the first weeks of life; whereas JMML is an aggressive disorder requiring hematopoietic stem cell transplantation, MPD/NS may resolve without treatment and cases with spontaneous remission have also been reported. Two cases of NS with hematologic disorders are described. Diagnosis of the syndrome was confirmed by the identification of earlier reported germline missense mutations in the PTPN11 gene. Splenomegaly in 1 patient and leukocytosis, monocytosis and "in vitro" culture assays consistent with JMML in both were the most salient hematologic features. After a 24-month follow-up, these 2 infants continue to improve and JMML has been ruled out. Splenomegaly persists in 1 patient and monocytosis in both, but without signs of malignancy, thereby suggesting abnormal hematopoiesis or MPD/NS, as described in NS.
Bastida
Pilar
P
Department of Pediatric Oncology and Hematology, Hospital Universitario Materno-Infantil Vall d'Hebron, Barcelona, Spain. pbastida@vhebron.net
García-Miñaúr
Sixto
S
Ezquieta
Begoña
B
Dapena
José Luis
JL
Sanchez de Toledo
José
J
D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics / Q000628:therapy; D008297:Male; D020125:Mutation, Missense; D009196:Myeloproliferative Disorders / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D009634:Noonan Syndrome / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics
C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11