Distinctive metaphyseal chondrodysplasia with severe distal radius and ulna involvement (upper extremity mesomelia) and normal height.

Metaphyseal chondrodysplasias (MCD) are skeletal disorders characterized by metaphyseal irregularities and, usually, by short stature. In MCD, wide heterogeneity exists with regard to clinical and radiological changes. We report on a patient with clinical and radiological findings of MCD who had coxa valga and normal height with metaphyseal involvement of the long bones. The short radii and ulnae showed a very severe change in their distal metaphyses, leading to mesomelic shortening confined to the upper limbs. Hematological, ophthalmological, and hearing examinations were normal. This type of MCD appears to represent a yet undescribed syndrome.

Previously undescribed nonsense mutation in SHH caused autosomal dominant holoprosencephaly with wide intrafamilial variability.

Holoprosencephaly (HPE) is the most common developmental defect of the forebrain and midface in humans, with a frequency of 1/16,000 live births. Different genes are implicated in the pathogenesis of HPE; these include SHH, ZIC2, SIX3, TGIF, and human DKK1. We describe here a family with recurrence of autosomal dominant HPE in different members showing a wide clinical variability. The mother presents a single central maxillary incisor and mild hypotelorism as signs of the diseases, while three of her sons were affected by HPE. By direct sequencing and restriction analysis of exon 2 of the SHH gene, we have identified a previously undescribed nonsense mutation at codon 128 (W128X). The identification of this mutation allowed us to give a prenatal diagnosis in this family and confirms a wide intrafamilial variability in the phenotypic spectrum.

Meier-Gorlin syndrome (ear-patella-short stature syndrome) in an Italian patient: clinical evaluation and analysis of possible candidate genes.

We report on an Italian boy with the Meier-Gorlin syndrome (ear-patella-short stature syndrome). This rare autosomal recessive disorder comprises the triad of microtia, absent patellae, and growth retardation with prenatal onset. The patient had also an acute torsion of his left spermatic cord, a condition related to a congenital defect of the tunica vaginalis. Because this syndrome had been suggested as the human equivalent of the short ear mouse [Lacombe et al., 1994: Ann. Genet. 37:184-191], a mutation analysis of the BMP5 gene was performed and found normal. The LMX1B and the SHOX genes were also evaluated considering the absent patellae and short stature, respectively, and were found normal as well.