Deletions of the short arm of chromosome 6 are relatively rare, the main features being developmental delay, craniofacial malformations, hypotonia, and defects of the heart and kidney, with hydrocephalus and eye abnormalities occurring in some instances. We present the molecular cytogenetic investigation of six cases with 6p deletions and two cases with unbalanced translocations resulting in monosomy of the distal part of 6p. The breakpoints of the deletions have been determined accurately by using 55 well-mapped probes and fluorescence in situ hybridization (FISH). The cases can be grouped into two distinct categories: interstitial deletions within the 6p22-p24 segment and terminal deletions within the 6p24-pter segment. Characteristics correlating with specific regions are: short neck, clinodactyly or syndactyly, brain, heart and kidney defects with deletions within 6p23-p24; and corneal opacities/iris coloboma/Rieger anomaly, hypertelorism and deafness with deletions of 6p25. The two cases with unbalanced translocations presented with a Larsen-like syndrome including some characteristics of the 6p deletion syndrome, which can be explained by the deletion of 6p25. Such investigation of cytogenetic abnormalities of 6p using FISH techniques and a defined set of probes will allow a direct comparison of reported cases and enable more accurate diagnosis as well as prognosis in patients with 6p deletions.

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Objectives: To describe the clinical findings and natural history in 22 carriers of an R460H mutation in the transforming growth factor b receptor 2 gene (TGFbR2) from a five-generation kindred ascertained by familial aortic dissection. Methods: 13 of the confirmed carriers were interviewed and examined, and information about the remaining carrier was obtained from medical records. Clinical information about deceased individuals was obtained, when possible, from postmortem reports, death certificates and medical records. Results: There have been eight sudden deaths; the cause of death was aortic dissection in all six cases in which a postmortem examination was performed. Three individuals had undergone aortic replacement surgery. Dissection had occurred throughout the aorta, and in one case in the absence of aortic root dilatation. Subarachnoid haemorrhage, due to a ruptured berry aneurysm, had occurred in two individuals. Four gene carriers and one deceased family member who were investigated had tortuous cerebral blood vessels. One had tortuous vertebral arteries, two had tortuous carotid arteries and one a tortuous abdominal aorta. Two individuals were found to have a brachiocephalic artery aneurysm and a subclavian artery aneurysm, respectively. Conclusions: Despite the predisposition to aortic dilatation and dissection, individuals did not frequently manifest the skeletal features of Marfan syndrome, with the exception of joint hypermobility. No one individual had ocular lens dislocation. Striae and herniae were common. There was some overlap with Ehlers-Danlos syndrome type 4, OMIM 130050, with soft translucent skin, which is easily bruised. Other features were arthralgia, migraine and a tendency to fatigue easily, varicose veins and prominent skin striae. This family provides further evidence that mutations in TGFbR2 cause a distinct syndrome that needs to be distinguished from Marfan syndrome to direct investigation and management of patients and shows the natural history, spectrum of clinical features and variable penetrance of this newly recognised condition.

We describe a 32 year old male with a distal 6p24.3->pter deletion. He has specific developmental anomalies of the anterior chamber ofthe eye and a cleft uvula which is consistent with the recent localisation of genes for iris development and orofacial clefting to distal 6p. In addition he has progressive sensorineural deafness and this may localise a gene for deafness to this region. We conclude that a refined distal 6p deletion syndrome exists and includes a characteristic facial appearance with hypertelorism, downward slanting palpebral fissures, tented mouth, smooth philtrum, palatal malformation, ear anomalies, anterior chamber eye defects, progressive sensorineural deafness, cardiac defects, abdominal herniae, small external genitalia, and motor and speech delay. ( Med Genet 1998;35:685-689)

The 22q13 deletion syndrome is associated with global developmental delay, absent or delayed speech, and generalised hypotonia. In this study, the size and nature of 22q13 deletions (n ¼ 9) were studied in detail by high-resolution chromosome specific array-based comparative genomic hybridisation (array CGH). The deletion sizes varied considerably between the different patients, that is, the largest deletion spanning 8.4 Mb with the breakpoint mapping to 22q13.2 and the smallest deletion spanning 3.3 Mb with the breakpoint mapping to 22q13.31. In one case, a unique subtelomeric 3.9 Mb deletion associated with a 2.0 Mb duplication of 22q13 was observed, adding to a growing number of similar cases identified for other chromosome ends. Remarkably, this patient had signs suggestive of retinitis pigmentosa, which has never been reported before in the 22q13 deletion syndrome. The identification of two pairs of recurrent proximal breakpoints on 22q13 suggests that these specific regions may be prone to recombination, due to yet unknown genome architectural features. In addition to the copy number changes on 22q13, a duplication of B330 kb on 22q11.1 was observed and shown to be a genetic large-scale copy number variation without clinical consequences. The current study failed to reveal relationships between the clinical features and the deletion sizes. Global developmental delay and absent or severely delayed speech were observed in all patients, whereas hypotonia was present in 89% of the cases (8/9). This study underscores the utility of array CGH for characterising the size and nature of subtelomeric deletions, such as monosomy 22q13, and underlines the considerable variability in deletion size in the 22q13 deletion syndrome regardless of the clinical phenotype.