Bilginturan et al. (1973) described a 'new' form of brachydactyly manifested by shortening of both phalanges and metacarpals and associated, probably as a pleiotropic effect, with hypertension. An extensive pedigree was well documented.
Schuster et al. ... Bilginturan et al. (1973) described a 'new' form of brachydactyly manifested by shortening of both phalanges and metacarpals and associated, probably as a pleiotropic effect, with hypertension. An extensive pedigree was well documented. Schuster et al. (1996) stated that the family reported by Bilginturan et al. (1973) lived in a remote area on the northeastern Black Sea coast of Turkey. Some members were residing in Germany. Schuster et al. (1996) performed a comprehensive medical examination on 6 members (5 affected and 1 unaffected) of this Turkish family. None of them was being treated for hypertension at the time of the study. The affected individuals were not salt sensitive and the humoral responses (including renin, aldosterone, and catecholamine) to volume expansion and contraction were normal, thus resembling essential hypertension (145500) and suggesting that the renin-angiotensin-aldosterone and the sympathetic nervous systems may not be responsible for the hypertension. Schuster et al. (1996) suggested that a not-yet-appreciated mechanism of blood pressure elevation was possibly involved. Bahring et al. (1996) demonstrated loops in the posterior/inferior cerebellar artery by magnetic resonance imaging (MRI) angiography of the posterior fossa vessels in 15 patients with this syndrome. It was present bilaterally or unilaterally in all affected individuals and in none of the unaffected members of the kindred. Bahring et al. (1996) speculated that neurovascular compression resulting from the looping might be responsible for the hypertension. Chitayat et al. (1997) reported 2 families with this disorder. All affected members of the first family had proportionate short stature, whereas the propositus and the affected relatives in the second family were only short compared to unaffected relatives. Hypertension was medically responsive in all cases. The propositus in the second family had poor compliance and a striking retinal arteriopathy. Hattenbach et al. (1998) reported the ophthalmologic findings in all 29 affected members of a Turkish kindred. Other than markedly elevated blood pressures and the residua of stroke in a few subjects, the apparent lack of end-organ damage was striking, including the normal-appearing fundi. Systolic blood pressures ranged from 110 to 250 mm Hg, while diastolic blood pressures ranged from 100 to 150 mm Hg in affected individuals. In all affected subjects, the fundi were only minimally altered or clinically normal. All 3 fluorescein angiograms were normal. Despite severe hypertension since childhood, the patients showed no signs of hypertensive retinopathy. In a review of the clinical and genetic features of autosomal dominant hypertension and brachydactyly, Luft et al. (2003) noted that magnetic resonance angiographic studies in 15 hypertensive affected and 12 normotensive unaffected members of the Turkish family originally described by Bilginturan et al. (1973) demonstrated neurovascular contact in all 15 affected individuals and none of the unaffected individuals (Naraghi et al., 1997). All of the affected individuals had left-sided posterior inferior cerebellar artery or vertebral artery loops contacting the ventrolateral medulla, and 6 had bilateral neurovascular contact. Linkage analysis for the 2 traits (hypertension-brachydactyly and neurovascular contact) with chromosome 12p markers yielded a lod score of 9.2, making the odds that these 2 traits are linked to this locus greater than 1,000,000,000:1.
In 4 families and 1 individual with hypertension and brachydactyly, including the Turkish family originally reported by Bilginturan et al. (1973) and the 2 families previously described by Chitayat et al. (1997), from the United States and Canada, ... In 4 families and 1 individual with hypertension and brachydactyly, including the Turkish family originally reported by Bilginturan et al. (1973) and the 2 families previously described by Chitayat et al. (1997), from the United States and Canada, respectively, Bahring et al. (2008) performed in vitro transcription/translation experiments with ESTs located within a common inverted region on chromosome 12p but found no peptide-related molecules. Quantitative RT-PCR showed that 2 products sharing 1 exon were exclusively expressed in nonaffected individuals, and expression in affected individuals was completely abolished. RNA secondary prediction of that single exon resulted in a stable stem-loop structure known to be essential for microRNA processing. Bahring et al. (2008) suggested that microRNA expression in affected individuals may lead to complete downregulation of a spliced transcript.