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J Clin Endocrinol Metab. 2006 Jan;91(1):300-6. Epub 2005 Nov 1.

Noonan syndrome: relationships between genotype, growth, and growth factors.

Author information

1
Department of Pediatrics, University Hospital, 49933 Angers, France. jmlimal@chu-angers.fr

Abstract

CONTEXT:

Half of the patients with Noonan syndrome (NS) carry mutation of the PTPN11 gene, which plays a role in many hormonal signaling pathways. The mechanism of stunted growth in NS is not clear.

OBJECTIVE:

The objective of the study was to compare growth and hormonal growth factors before and during recombinant human GH therapy in patients with and without PTPN11 mutations (M+ and M-).

SETTING, DESIGN, AND PATIENTS:

This was a prospective multicenter study in 35 NS patients with growth retardation. Auxological data and growth before and during 2 yr of GH therapy are shown. GH, IGF-I, IGF binding protein (IGFBP)-3, and acid-labile subunit (ALS) levels were evaluated before and during therapy.

RESULTS:

Molecular investigation of the PTPN11 coding sequence revealed 12 different heterozygous missense mutations in 20 of 35 (57%). Birth length was reduced [mean -1.2 sd score (SDS); six m+ and two m- were < -2 SDS] but not birth weight. M+ vs. M- patients were shorter at 6 yr (P = 0.04). In the prepubertal group (n = 25), GH therapy resulted in a catch-up height SDS, which was lower after 2 yr in M+ vs. M- patients (P < 0.03). The mean peak GH level (n = 35) was 15.4 +/- 6.5 ng/ml. Mean blood IGF-I concentration in 19 patients (11 m+, eight m-) was low (especially in M+) for age, sex, and puberty (-1.6 +/- 1.0 SDS) and was normalized after 1 yr of GH therapy (P < 0.001), without difference in M+ vs. M- patients. ALS levels (n = 10) were also very low. By contrast, the mean basal IGFBP-3 value (n = 19) was normal.

CONCLUSIONS:

In NS patients with short stature, some neonates have birth length less than -2 SDS. Growth of M+ is reduced and responds less efficiently to GH than M- patients. The association of low IGF-I and ALS with normal IGFBP-3 levels could explain growth impairment of M+ children and could suggest a GH resistance by a late postreceptor signaling defect.

PMID:
16263833
DOI:
10.1210/jc.2005-0983
[Indexed for MEDLINE]

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