T he insulin-like growth factors (IGFs; somatomedins) comprise a family of peptides that play important roles in mammalian growth and development. The principal members of this family are IGF1 and IGF2. IGF1 (somatomedin C), a 70 residue basic polypeptide, mediates many of the growth promoting actions of growth hormone (GH) and has metabolic and mitogenic effects.1 The major source of circulating IGF1 is the liver, but it is also produced in a wide variety of tissues and has endocrine and paracrine modes of action. The mature IGF1 peptide has A, B, C, and D domains with homology to insulin, and is highly conserved.2 It is produced as an inactive precursor, pre-pro-IGF1, with an additional carboxyterminal E region that plays an important role in the maturation of normal IGF1 peptide. This regulatory region is obtained by alternative splicing of the last two exons. IGF1 resides on the long arm of chromosome 12 (12q 22-24.1), 3 and several molecular studies have demonstrated that the structure of this gene is very complex. The gene contains six exons, which extend over more than 85 kb on chromosomal DNA. For human IGF1, two potential primary translation products exist: IGF1A and IGF1B, with sizes of 153 and 195 amino acids respectively. The two precursors are synthesised from distinct messenger RNAs produced by alternative splicing of the primary transcript. IGF1A mRNA contains exons 1, 2, 3, 4, and 6 of the human IGF1 gene while IGF1B is encoded by exons 1, 2, 3, 4, and 5. It has been speculated that IGF1B plays the major role during intrauterine growth, while the same function during postnatal growth is taken over by IGF1A. 4 Recent studies have focused attention on the genetic causes of growth alterations. Mutations involving the molecular structure of GH 5 or the function of the GH receptor 6 have been described. Recently, a partial deletion of the gene for IGF1, resulting in intrauterine growth failure plus severe post-natal growth retardation, sensorineural deafness, and mental retardation has been found. 7 In this study, we describe a new case of IGF1 deficiency associated with sensorineural deafness, severe pre-and post-natal growth failure, and delayed psychomotor development produced by a novel transversion TRA, which disrupts the normal consensus sequence for the polyadenylation site in the 39 untranslated region of exon 6 of IGF1, leading to altered mRNA processing, which could account for the extremely low IGF1 circulating levels and for the clinical findings. METHODS Case reportThe patient was born at 39 weeks' gestation by caesarean section because of poor fetal growth. The pregnancy had until then been uneventful. The birth weight was 1480 kg (24SD), length was 41 cm (26.5 SD), and the head circumference was 26.5 cm (,5th percentile). Hypoglycaemia and icterus were not reported. His parents were second cousins and the family history showed several miscarriages. His mother was 153 cm tall (5th percentile) and his father was 163 cm (5th percentile). His healthy sister, at the age of 9 years, was ...

Children with IDDM have normal onset of puberty and normal sexual maturation. Even though final height falls within the normal percentiles, the diminished height gain after diagnosis requires further investigation.

To analyze possible early abnormalities in bone resorption in type 1 diabetes mellitus the urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline was evaluated by immunoassay in 26 prepubertal diabetic patients (mean age 7.8 ± 1.6 years, mean duration 3.0 ± 1.1 years) and 46 healthy children (age 8.3 ± 1.3 years). Relationships with growth parameters (height-standard deviation score, body mass index and height velocity during the year preceding the study) and metabolic control were sought. Longitudinal and ponderal growth was normal in diabetic children. Urinary collagen crosslink excretion was 88.4 ± 25 nmol/mmol creatinine (median 86, range 44–146) in diabetic patients and 65.6 ± 19 nmol/mmol creatinine (median 61, range 32–108) in controls (p = 0.0002). It was positively influenced by diabetic status (beta = 20.5) and negatively by age (beta = –6.41), controlling by sex and BMI (p = 0.0001). A positive correlation was found between collagen crosslinks and blood glucose (r = 0.48, p = 0.01) or HbA1c levels (r = 0.44, p = 0.02) evaluated at the time of the study, while no significant correlation was found with the mean HbA1c values assessed in the last year or throughout the whole duration of diabetes. Collagen crosslink excretion was significantly increased in patients who presented worsening of their metabolic control in the last 3 months. No relationship was found with the duration of disease or growth parameters. In conclusion, the elevated urinary excretion of collagen crosslinks in diabetic children indicates that bone resorption may be disturbed. Poor metabolic control influences the increased rate of bone resorption and may expose growing diabetic patients to a risk of bone loss.

We report on a new case of a syndrome first described by Cantú et al. [1982: Hum Genet 60:36-41] comprising congenital hypertrichosis, "coarse" facial appearance, and mild osteochondrodysplasia. Our case has some unusual radiological findings, namely proximal and distal megaepiphyses of long bones and advanced bone age.