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These growth abnormalities in LS patients without IGF-I substitutive treatment includes postnatal average growth rates of one-half the expected during the first years of life[19], a small brain (with prominent forehead, reduced vertical dimension of the face and hypoplasia of the midfacies and the nasal bridge), a small heart and acromicria[203] together with underdevelopment of the muscular system that delays walking in three-fourth of patients[204, 205], osteopenia at all stages (despite normal sex hormone status) with increased occurrence of avascular necrosis of the femoral head[206], impair and weaken skin, hair and nail growth[207], blue sclera due to the decreased thickness of its connective tissue, allowing visualization of the underlying choroid[205], a puberty delay from 3 to 7 years[206], retardation in the maturation of dentition[206] and high-pitched voice[208]

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doi: 10.1007/s00251-011-0513-0 30 WeiskopfDAngeloMAde AzeredoELSidneyJGreenbaumJAFernandoANet al