Spondyloepiphyseal dysplasia, Omani type: further definition of the phenotype.

Spondyloepiphyseal dysplasia (SED), Omani type (OMIM 608637) is a recessively inherited skeletal dysplasia previously described in two distantly related families from the Republic of Oman. The phenotype consists of short stature, severe kyphoscoliosis, arthritic joints (elbows, wrists, knees), secondary large joint dislocations, rhizomelia, fusion of carpal bones and mild brachydactyly. Affected individuals were homozygous for a missense mutation, R304Q in CHST3 that encodes the enzyme chondroitin 6-O-sulfotransferase-1 (C6ST-1). This enzyme mediates the sulfation of proteoglycans, particularly chondroitin sulfate (CS), in the extracellular matrix of cartilage. Here we describe the identification of a mutation (857T > C predicting the substitution L286P) in CHST3 in a Turkish family and extend the clinical phenotype of SED-Omani type to include congenital joint dislocation, club feet, ventricular septal defect, deafness, metacarpal shortening and accessory carpal ossification centers. Fibroblasts and urine obtained from affected patients demonstrated negligible levels of 6-O-sulfated GalNAc residue in CS. Furthermore, the 6-O-sulfotransferase activity of cloned C6ST-1 into which the L286P mutation had been introduced was dramatically reduced, confirming the pathogenicity of this substitution. These results indicate that the clinical consequences of a deficiency of 6-O-sulfation in CS can be varied and that a clinical spectrum may exist similar to that seen in other skeletal dysplasias characterized by disorders of proteoglycan sulfation.

[Intra-uterine death caused by fetal akinesia]. / Intra-uteriene sterfte door foetale bewegingsarmoede: het belang van diagnostiek na een vruchtdood.

BACKGROUND: When two successive pregnancies end in intra-uterine fetal death (IUFD), the question of whether it is coincidental or if there is an underlying abnormality arises. Although diagnostic investigations into the underlying cause are not always carried out after IUFD, they are recommended by the professional body. CASE DESCRIPTION: A 28-year-old female attended our gynaecology outpatient clinic for a second opinion following two intra-uterine fetal deaths. Her own treating physician was of the opinion that there was no connection between the two IUFDs. After a multidisciplinary evaluation, the phenotype fetal akinesia deformation sequence (FADS) was diagnosed in both cases. This is a rare, clinically and aetiologically heterogeneous group of disorders. Thereafter the patient and her husband were offered specific pre-conception counseling. CONCLUSION: Every IUFD justifies systemic and multidisciplinary investigation to determine any underlying aetiology such as FADS. This may contribute to better pre-conception advice and prenatal individualised diagnostics in a subsequent pregnancy.

Prenatal diagnosis in two cases of de novo complex balanced chromosomal rearrangements. Three-year follow-up in one case.

We report two cases of apparently balanced complex de novo chromosomal rearrangements (BCCR) detected prenatally at 17 weeks and 10 weeks of gestation, respectively. Chromosomes were studied using GTG-banding and fluorescent in situ hybridization (FISH). In one case four chromosomes and in the other case three chromosomes were involved in the rearrangements. One of the pregnancies was terminated and no external or internal showed no abnormalities. The child is now 3 years old and has neither congenital anomalies nor evidence of delayed psychomotor development.