Search

Mutations in the gene for the insulin-like growth factor I receptor may cause growth retardation in babies and children, according to a study of 135 children. Among the 92 children who were short, researchers found two children who had the mutation. This mutation was not present in the 43 children with normal birth weights.

The majority of the vertebrate skeleton develops through the process of endochondral ossification and involves successive steps of chondrogenesis, chondrocyte proliferation, and hypertrophic chondrocyte differentiation. Interruption of this program through gene mutations and hormonal or environmental factors contributes to numerous diseases, including growth disorders and chondrodysplasias. While a large number of growth factors and hormones have been implicated in the regulation of chondrocyte biology, relatively little is known about the intracellular signaling pathways involved. Recent data provide novel insights into the mechanisms governing acquisition of new phenotypes within the chondrogenic program and suggest multiple pivotal roles for members of the mitogen-activated protein kinase family and their downstream targets in cartilage development. These data are summarized and discussed here.

Research has been conducted on the hypomorphic Rad50 mutant mice. Results indicate that these mice exhibit growth defects and cancer predisposition.

Objective. Many short-statured children lack an etiologic explanation for their retarded growth. Recenfiy, uniparental disomy (UPD), the inheritance of both chromosomes of a chromosome pair from only 1 parent, has been associated with short stature for many chromosomes. Silver-Russell syndrome (SRS) represents an extreme syndrome of intrauterine growth retardation (IUGR) and slight dysmorphic signs, and maternal UPD of human chromosome 7 (matUPD7) has been observed in approximately 10% of SRS cases. In addition, matUPD7 has been reported in patients with only slight dysmorphic features and prenatal or postnatal growth retardation. The objectives of this study were to study the role of matUPD7 in growth failure of unknown cause and in cases of SRS, and to evaluate the efficiency of genetic testing for matUPD7 as a diagnostic tool. Methods. DNA samples were studied from 205 children, 92 girls and 113 boys, with short stature of unknown cause and their parents. The patient cohort included 39 cases of SRS, 91 patients with IUGR and subsequent postnatal short stature, and 75 patients with postnatal growth retardation only. MatUPD7 was screened for by genotyping DNA samples from the patient, mother, and father with 13 chromosome-7-specific polymorphic microsatellite markers. Results. Six (3%) of 205 matUPD7 cases were observed exclusively among 39 (15%) SRS patients studied. Patients with IUGR and/or postnatal growth retardation and with dysmorphic features did not reveal cases of matUPD7. Conclusions. Our results indicate that matUPD7 cases are predominantly observed among patients meeting the criteria of SRS, and matUPD7 is not a common cause for growth retardation. Genetic screening for cases of matUPD7 among growth-retarded patients should be focused on patients with severe IUGR and features of SRS. In addition, matUPD7 screening is advisable in individuals with cystic fibrosis and other recessive disorders mapped to chromosome 7 who have unusually short stature. Pediatrics 2002;109:441-448; Silver-Russell syndrome, growth retardation, matUPD7, imprinting., ABBREVIATIONS. SDS, standard deviation scores; IUGR, intrauterine growth retardation; SRS, Silver-Russell syndrome; PNGR, postnatal growth retardation; GH, growth hormone; UPD, uniparental disomy; matUPD7, maternal UPD of chromosome 7; patUPD7, paternal [...]

The case of a man with excessive growth illustrates the role that estrogen plays in bone maturation. He continued to grow after the age of 18 and by the age of 31, his height was in the 97th percentile. At that time he was evaluated for persistent growth, infertility and bone pain. X-rays revealed that his bones had not matured and continued to grow. His testosterone concentration was normal and his condition was unchanged by six months of testosterone treatment. Genetic analysis revealed a mutation in the gene for cytochrome P-450 aromatase. When his height exceeded the 97th percentile he was treated with estrogen, which caused his bones to mature.

Short children with normal levels of growth hormone (GH) and low levels of GH-binding protein may have mutations of the GH-receptor gene. Researchers analyzed the DNA of 24 normal adults and 14 short children with low GH-binding protein levels. When they found a mutation in the children the researchers tested the binding ability of the GH receptor. Mutations of the GH-binding receptor gene were found in 4 of the 14 children and none of the normal adults. Most of the mutations involved replacements of nucleic acids that altered the part of the GH receptor that lies outside of the cell. Three of the four children with mutations partially responded to GH therapy, indicating that the mutations conferred partial insensitivity on the receptor. People with complete receptor insensitivity do not respond to GH therapy and have Laron dwarfism.

Byline: Nagwa. Ismail, Nermeen. Metwaly, Fatma. El-Moguy, Mona. Hafez, Soha. El Dayem, Tarek. Farid Background: Empty sella (ES) may be associated with variable clinical conditions ranging from the occasional discovery [...]