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The authors observed a patient with a cryptic subtelomeric de novo balanced translocation 46,XY.ish t(11;20)(p15.4;q13.2) presenting with severe mental retardation, muscular hypotonia, seizures, bilateral sensorineural hearing loss, submucous cleft palate, persistent ductus Botalli, unilateral cystic kidney dysplasia and frequent infections.Fluorescence in situ hybridisation mapping and sequencing of the translocation breakpoints showed that no known genes are disrupted at 20q13.2 and that ST5 (suppression of tumorigenicity 5; MIM 140750) is disrupted on 11p15.4. By quantitative PCR from different human tissues, the authors found ST5 to be relatively evenly expressed in fetal tissues. ST5 expression was more pronounced in adult brain, kidney and muscle than in the corresponding fetal tissues, whereas expression in other tissues was generally lower than in the fetal tissue. Using RNA in situ hybridisation in mouse, the authors found that St5 is expressed in the frontal cortex during embryonic development. In adult mouse brain, expression of St5 was especially high in the hippocampal area and cerebellum.Hence, the authors suppose that ST5 plays an important role in central nervous system development probably due to disturbance of DENN-domain-mediated vesicle formation and neurotransmitter trafficking. Thus, these findings implicate ST5 in the aetiology of mental retardation, seizures and multiple congenital anomalies.

Three unrelated patients with identical radiological features are presented. Hypotonia was noted at birth and one patient was diagnosed as having congenital fibre type disproportion in the neonatal period. Later muscle biopsies, however, were entirely normal. All patients, now in their teens and twenties, are of normal intelligence, show striking epiphyseal and metaphyseal changes of the long bones, and have joint laxity and multiple dislocations of large joints, which are particularly incapacitating at the knees. These three cases represent a sporadic, previously unreported skeletal dysplasia with spondyloepimetaphyseal distribution and multiple large joint dislocations.

This report describes an 11 month old female baby with features of pentasomy X. A molecular and cytogenetic evaluation revealed that her karyotype was 49,XXXXX and her extra X chromosomes were of maternal origin. She has muscular hypotonia, mental retardation, a cleft palate, mild hydrocephalus as a result of dilatation of both lateral ventricles, hyperextensible elbow joints, proximal radioulnar synostosis, clinodactyly of the fifth finger, valgus of the feet, and small hands and feet. In addition, she has a persistent pupillary membrane and congenital chorioretinal atrophy. The pathogenesis of pentasomy X is not clear at present, but it is thought to be caused by successive maternal non-dysjunctions.

Williams-Beuren syndrome (WBS, OMIM 194050) is a microdeletion syndrome caused by hemizygosity for multiple genes in 7q11.23 including the elastin locus ( ELN ).1,2 The classical WBS phenotype comprises elastin arteriopathy (supravalvular aortic stenosis and/or peripheral pulmonary stenosis), connective tissue abnormalities (for example, abnormal joint mobility, hernia and diverticula, hoarse voice), and a particular facial appearance (supraorbital fullness, stellate pattern of the iris, short nose with long philtrum, full lips, and wide mouth). Other frequent features are growth and psychomotor retardation with muscular hypotonia, limited visuospatial cognition, and specific language as well as behavioural abnormalities (overfriendliness and anxiety disorders, hypersensitivity to sounds).3–5 Endocrine and metabolic disturbances (infantile hypercalcaemia) may occur. Despite at least 21 genes having been identified in the common 1.5 Mb deletion interval in humans,6 their individual contribution to the multisystem phenotype of WBS is unclear. So far, only the gene coding for elastin ( ELN ) has been proven to be causally involved7: ELN is deleted in all WBS patients with a microdeletion 7q11.23 who have been reported to date. However, hemizygosity for ELN alone does not cause WBS, but isolated supravalvular aortic stenosis (SVAS).8 Hence, haploinsufficiency for ELN is necessary but not sufficient for WBS. Molecular dissection of the WBS phenotype is hindered by the fact that over 95% of patients with the classical phenotype carry an apparently identical ~1.5 Mb deletion interval.9–11 This constant size is explained by non allelic-homologous recombination between duplicons flanking the deletion interval.12 The presence of these direct repeats is assumed to be a predisposing factor for the WBS microdeletion that occurs with a frequency of approximately 1 in 20 000 liveborn children.12 So far, several cases of either classical WBS or SVAS with or without cognitive deficits have been found to …

The proband, the first child of unrelated parents, was noted in infancy to have microcephaly, developmental delay, dysmorphic facies, hypotonia, a small penis with cryptorchidism, and a fixed flexion deformity of his left index finger. His maternal uncle is severely retarded and has similar dysmorphic facies.

We report a sibship of two brothers and one sister with the osteoporosis-pseudoglioma syndrome and congenital heart disease. They presented in infancy with visual impairment and psychomotor retardation. Major features included bilateral cataracts, generalised osteopenia, severe platyspondyly, borderline mental retardation, muscular hypotonia, joint laxity, and ventricular septal defect. Parental consanguinity and affected sibs of both sexes strongly suggested autosomal recessive inheritance. Analysis of the present and previously reported cases showed a wide range of interfamilial variability which may point to the existence of multiple allelism or genetic heterogeneity in this syndrome.

Nineteen girls with characteristic features of Rett's syndrome, including normal initial development, regression at about 12 months of age, repetitive hand movements, and severe mental handicap were studied. This represents an estimated incidence of one in 30 000 live births (one in 15 000 girls) in the west of Scotland. Although the children were often initially considered to be autistic, they did not conform to this diagnosis as they made good personal contact within the limits of their mental development. The developmental regression was sometimes falsely attributed to vaccination. Each child showed striking involuntary movements and abnormality of tone, varying from hypotonia, which was found only in the youngest, to rigidity, which was common in older girls; this permitted classification into three clinical subtypes. The abnormalities were highly suggestive of an extrapyramidal disorder, and this has implications for further research and possible treatment.

Two patients with the XXXXY syndrome are presented. Both boys are mentally retarded with short stature, muscular hypotonia, and hypogonadism. A constant feature of this syndrome is a varying degree of epiphysial dysplasia probably secondary to hypotonia and growth deceleration.

A case of ring 17 chromosome in a 5-month-old male infant is investigated and compared with five previously reported cases. The findings commonly observed in these patients include mental and motor retardation, seizures, short stature, muscular hypotonia, and microcephaly among others. Dermatoglyphic studies showed an increased number of ulnar loops. More interestingly, bilateral transverse hypothenar creases were noted. Two of the reported cases also had unspecified genital abnormalities. The variation in clinical findings among these patients may be explained by a difference in the breakpoints on chromosome 17.