ESPE Abstracts

Background: 3-M syndrome is an autosomal recessive primordial growth disorder characterized by severe prenatal and postnatal growth retardation, normal mental development, unusual facial features and skeletal abnormalities. Mutations in the CUL7, OBSL1 and CCDC8 genes are responsible for this syndrome. In literature a modest response to GH treatment in 3M children is reported without a significant improvement in the final height, suggesting a picture of GH insensitivity.

Objective and hypotheses: To describe the 1 year results of r-hGH treatment in a patient with 3M syndrome and GH deficiency.

Results: Here we describe the case of an Italian girl born from non consanguineous parents, full term, small for gestational age (weight 2120 g: <3rd centile; length 40.5 cm: <3rd centile). She presented postnatal growth retardation, hip dysplasia, hyperextensible joints and normal mental development. Therefore clinical diagnoses of 3M syndrome was suspected and then confirmed by the finding of a CUL7 mutation in compound heterozygosity (c. 3750delA +3753_3762 del and c.4814delG: this last mutation unreported). At the age of 4 years and 4 months the height was −2.74 SDS, growth velocity −2.60 SDS. GH stimulation tests with arginine and clonidine showed a peak of 5.95 and 4.97 ng/ml, respectively. Not alterations in size, morphology and impregnation of pituitary gland were found at MRI. Therefore r-hGH treatment was started at 0.30 mg/kg per week. After 6 months of therapy we report a significant catch up growth: height −2.16 SDS and growth velocity 0.64 SDS; after 1 year of treatment: height was −1.80 SDS.

Conclusion: Even if a longer follow up is necessary to confirm this finding, our data may suggest to study GH axis in 3M syndrome for the possibility of an interindividual response to GH treatment in these patients.