Deletion of the short arm of chromosome 9

A partial deletion of the short arm of chromosome 9 is reported in a female newborn and a 12.5 yearold male. The features expressed by both patients, and especially the peculiar type of the craniofacial dysmorphism, confirm the existence of a typical clinical syndrome associated with this partial autosomal monosomy.     

Silver-Russell syndrome

Silver-Russell syndrome (SRS) is characterised by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, triangular face, asymmetry and feeding difficulties. As many of these features are non-specific, clinical diagnosis of SRS remains difficult. Hypomethylation of the imprinting control region (ICR) 1 on chromosome 11p15 and maternal uniparental disomy (mUPD) for chromosome 7 are found in up to 60% and around 5-10% of patients with SRS, respectively. Patients with ICR1 hypomethylation are more likely to have classical features of SRS, including asymmetry; patients with mUPD7 are more likely to have learning difficulties, particularly speech problems, although these are usually mild. As features vary widely in severity, clinicians should have a low threshold for genetic investigation of patients with features suggestive of SRS.     

Deletion of the short arm of the X chromosome: A hereditary form of Turner syndrome

In the mothers of two girls with Turner syndrome due to a deletion of the short arm of an X chromosome, the same chromosomal anomaly was detected. Both mothers and daughters had short stature but normal pubertal development. Short parents and normal pubertal development do not exclude Turner syndrome in a girl with small stature.     

Genetic and epigenetic findings in Silver-Russell syndrome

Silver-Russell syndrome (SRS) is a genetically and clinically heterogeneous disease which is mainly characterized by pre- and postnatal growth restriction. The typical SRS phenotype furthermore includes a relative macrocephaly, a triangular shaped face, body asymmetry, clinodactyly of the fifth finger and other less constant features. In about ~50% of patients (epi)genetic alterations involving chromosomes 7 and 11 can be detected. The major finding (~44%) is a hypomethylation of the imprinting control region 1 (ICR1) in 11p15.5 affecting the expression of H19 and IGF2. 4-10% of the patients carry a maternal UPD of chromosome 7 (UPD(7)mat). In a few cases chromosomal rearrangements have been reported. The diagnostic workup should therefore include 11p15 testing, UPD(7)mat analysis and molecular karyotyping. The recurrence risk is generally low in SRS but it can strongly increase in case of familial epimutations or chromosomal rearrangements. Interestingly, in ~7% of 11p15 hypomethylation carriers, hypomethylation of additional imprinted loci can be detected. Clinically, patients with hypomethylation at multiple loci do not differ from those with isolated ICR1 hypomethylation whereas the UPD(7)mat patients generally show a milder phenotype. Nevertheless, an unambiguous (epi)genotype-phenotype correlation can not be delineated. Furthermore, the pathophysiological mechanisms resulting in the SRS phenotype still remain unknown despite the recent progress in deciphering molecular defects in the disease.     

Heart disease associated with deletion of the short arm of chromosome 18

Summary Deletion of the short arm of chromosome 18 produces a highly variable phenotype. Mental retardation, short stature, and an abnormal facies are invariably present. About 9% of patients with this syndrome have cardiac pathology.     

Silver Russell 综合征1例

患儿,男,7岁2月,因左右肢体不对称6年余入院。患儿系第一胎,第一产,足月顺产,无窒息抢救史,出生体重2505g,身长49cm。患儿出生7～8个月时,发现其手脚左右不对称,左侧大于右侧,活动灵活,1周岁会走路,说话,婴幼儿期出汗较多,无空腹晕厥史,现读小学二年级,成绩良好,智力发育良好。     

Deletion of the long arm of the Y chromosome in an adolescent with short stature and hypogonadism

We describe a patient with short stature more than that expected for non-treated congenital adrenal hyperplasia due to nonclassic 21-hydroxylase deficiency with deletions in the long arm of the Y chromosome including the CGY gene and the AZF subregions.     

Deletion of the long arm of chromosome 18, primary hypothyroidism, Biermer's anemia and IgM hypogammaglobulinemia

We report the case of an adolescent girl who presents with the 18q-syndrome, primary hypothyroidism, pernicious anemia and IgM hypogammaglobulinemia. Her karyotype was performed during infancy because of malformations and showed deletion of the long arm of chromosome 18. The patient had been treated with levothyroxine (Elthyrone) since age 13 when primary hypothyroidism was documented. A close hematological follow-up was then undertaken due to the presence of anti-parietal cell antibodies. A megaloblastic anemia of sudden offset led to the diagnosis of pernicious anemia by age 16, which was confirmed by a positive Shilling's test. Recently, the patient was found to have antimicrosome antibodies and moderate IgM hypogammaglobulinemia.     

Silver-Russell syndrome. Observations in 20 patients

The growth and development data of 20 patients with the Silver-Russell syndrome (14 boys, 6 girls) were analyzed. Family history, pregnancy and delivery did not reveal any significant anomalies. Birth length was 44.0 +/- 3.0 cm (boys) and 43.8 +/- 2.1 cm (girls), birth weight 2.0 +/- 0.4 kg and 2.05 +/- 0.3 kg, respectively. At the time of diagnosis (mean age 4.1 +/- 2.2 years), height was -4.4, bone age -1.9, weight -3.7, and head circumference -1.5 standard deviations below the normal mean for age. Calculated or reached adult height corresponded to 82--94% of target height. Intelligence was normal in most patients. 8 had asymmetrical extremities, 3 an asymmetrical face. 7 of 14 boys had cryptorchidism (3 uni-, 4 bilateral), 2 incomplete masculinization, and 2 of 6 girls hypertrophy of the clitoris. Development of secondary sex characters was appropriate for bone age with exception of one boy, whose puberty was early. In 3 boys with completed pubertal development, testicular volume was small and gonadotropins (before and after LHRH) high. It is concluded that 1. the growth pattern in Silver-Russell syndrome is quite homogeneous, and rather accurate predictions are possible; 2. Intersexual genitalia do not seem to be related to endocrine factors, and 3. hypergonadotropic hypogonadism appears to be frequent in males.     

The search for the gene for Silver-Russell syndrome

Patients with Silver-Russell syndrome display intrauterine growth restriction and other dysmorphic features. No single genetic cause for this syndrome has been found, although there are a small number of familial cases and some patients with chromosomal rearrangements. Maternal uniparental disomy of chromosome 7 has been found in approximately 7% of patients with Silver-Russell syndrome. In five of these patients exhibiting maternal uniparental disomy, no common regions of isodisomy were found, thereby ruling out the expression of a recessive allele. It is most likely that one or more imprinted genes are responsible for the phenotype of Silver-Russell syndrome. Human chromosome 7 demonstrates homology with two imprinted regions on mouse chromosomes 6 and 11, which are equivalent to human chromosome regions 7q32 and 7p11-p13, respectively. We directly analysed the imprinting status of candidate genes from chromosome 7 that mapped to homologous imprinted regions in the mouse and also had a potential role in growth. The candidates were the genes that encode the epidermal growth factor receptor and the insulin-like growth factor binding proteins-1 and -3. All three of these candidate genes are localized to chromosome region 7p11-p13. Using intragenic polymorphisms as markers, we found that all three genes showed biallelic expression in different fetal tissues. Therefore, it is unlikely that these candidate genes are directly involved in producing the phenotype of Silver-Russell syndrome. Other candidates are under analysis, including two newly identified genes that are known to be imprinted.     

Cognitive abilities associated with the Silver-Russell syndrome.

There is no consensus opinion on whether or not cognitive impairments are found in the Silver-Russell syndrome. An investigation of a substantial sample was undertaken, using standardised assessments, in 20 boys and five girls aged 6.0 years to 11.8 years. Mean (SD) birth weights were -2.65 (0.95) SD scores, corrected for gestation. At evaluation the children had a mean (SD) age of 8.8 (1.8) years and a mean height of -2.26 (1.5) SD scores. Tests of cognitive abilities included assessments of general intelligence, reading and arithmetic attainments, and a cognitive processing task. Most had some degree of developmental delay: mean (SD) full scale IQ was 86 (24); 32% scored within the learning disability range (that is, IQ < 70); 40% were reading at least 24 months below their chronological age. Current head circumference correlated highly with full scale IQ. Assessments of special educational needs had been completed on 36%; 48% were receiving speech therapy. Approximately half of children with the Silver-Russell syndrome have significant impairment of their cognitive abilities.