Association of wilms tumor with spinal dysraphism.

Previous data suggested an association of vertebral anomalies with Wilms tumor. At the same time, vertebral midline fusion defects are often indicated by dermal anomalies over the spine. In the present study the prevalence of both occult spina bifida and cutaneous signs of spinal dysraphism was significantly higher in 50 Wilms patients than in 180 control children (18.0 versus 4.4%, p <.01, and 35.9 versus 17.5%, p <.02, respectively). Family investigations are needed to answer the question whether signs of spinal dysraphism in parents and sibs of patients may be regarded as indicators of an increased risk of Wilms tumor in the family.

Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia.

UNLABELLED: Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant skeletal dysplasia characterised by hypoplastic clavicles, patent fontanelles, short stature, tooth anomalies and other variable skeletal changes. Different mutations of the RUNX2/CBFA1 gene (MIM 600211) have been detected in patients with CCD. We investigated a mother and daughter with features of CCD presenting with reduced plasma alkaline phosphatase activity, increased urinary phosphoethanolamine excretion and decreased bone density. The latter findings were suggestive of hypophophatasia but mutation analysis showed no mutation in the tissue-nonspecific alkaline phosphatase gene (TNSALP; MIM 171760). However, a heterozygous mutation (Arg169Pro caused by nucleotide change 506G > C) was detected in the RUNX2 gene. Metabolic alterations gradually improved in both mother and daughter but bone-specific alkaline phosphatase remained low (less than 30% of normal) and mild phosphoethanolaminuria persisted. Recent studies in the Cbfa1 knock-out mouse showed decreased expression of alkaline phosphatase in differentiating bone. CONCLUSION: we suggest that the observed metabolic alterations are secondary to the RUNX2 gene mutation affecting early bone maturation and turnover. This is the first description of biochemical findings of hypophosphatasia in patients with cleidocranial dysplasia.

Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families.

Frontometaphyseal dysplasia is a rare genetic syndrome affecting the skeletal system and connective tissue. It is believed to be inherited as an X-linked trait. Features of frontometaphyseal dysplasia overlap with other skeletal dysplasias. Prominent supraorbital ridges, radiologic evidence of cranial hyperostosis, and flared metaphyses are characteristic. Scoliosis, a rare associated finding, is usually mild, and familial progressive scoliosis has not been reported so far. The skeletal dysplasia and the associated clinical findings show significant intra- and interfamilial variability. The syndrome has been suggested to be an allelic variant of the Melnick-Needles osteodysplasty, an X-linked (dominant) entity. We present two families with frontometaphyseal dysplasia, in which both males and females showed the facial and skeletal features of the syndrome in association with progressive scoliosis. Some of the affected members also had hearing loss and urogenital anomalies, supporting the existence of the recently suggested entity "fronto-otopalatodigital-osteodysplasty syndome".