A case report of severe tuberous sclerosis complex detected in utero and linked to a novel duplication in the TSC2 gene.

BACKGROUND: Disease severity is tremendously variable in tuberous sclerosis complex (TSC). In contrast with the detailed guidelines available for TSC diagnosis and management, clinical practice lacks adequate tools to evaluate the prognosis, especially in the case of in utero diagnosis. In addition, the correlation between genotypes and phenotypes remains a challenge, in part due to the large number of mutations linked to TSC. In this report, we describe a case of severe TSC diagnosed in utero and associated with a specific mutation in the gene tuberous sclerosis complex 2 (TSC2). CASE PRESENTATION: A mother was referred for a thorough investigation following the observation by ultrasound of cardiac abnormalities in her fetus. The mother was healthy and reported frequent, intense and long-lasting hiccups/spasms in the fetus. The fetus of gestational age 33 weeks and 4 days was found to have multiple cardiac tumors with cardiac ultrasound. Brain magnetic resonance imaging (MRI) performed in utero revealed the presence of sub-ependymal nodules and of abnormal signals disseminated in the white matter, in the cerebral cortex and in the cerebellum. Following diagnosis of definite TSC, pregnancy interruption was chosen by the parents. Genetic testing of the fetus exposed a duplication in exon 41 of TSC2 (c.5169dupA), which was absent in the parents. The autopsy ascertained the high severity of brain damage characterized by an extensive disorganisation of white and grey matter in most cerebral lobes. CONCLUSIONS: This case presentation is the first to depict the association between a de novo TSC2 c.5169dupA and multi-organ manifestation together with indications of a particularly high disease severity. This report can help physicians to perform early clinical diagnosis of TSC and to evaluate the prognosis.

Implanting telehealth network for paediatric cardiology: learning from the Quebec experience.

The implementation committee of the Quebec Child Telehealth Network was formed in 1997, with a mandate to build a network dedicated to the diagnosis of congenital cardiac disease via telemedicine. We devised criterions for selection to determine which peripheral centres would be linked by telemedicine to the university-based services for paediatric cardiology provided in the Canadian Province of Quebec. The criterions included: distance from a university centre, number of births per year, and presence of an already-established outreach clinic for paediatric cardiology. The Quebec Network became operational in 2000, and was composed of 32 peripheral centres and 4 university centres. A total of 363 transmissions of echocardiograms occurred over a 3-year period from January 2000 to December 2002. Peripheral centres located at a distance greater than 100 kilometres from a university centre were 8.5 times more likely to use the network. Criterions other than distance did not influence whether or not a peripheral centre used the network. Cardiac abnormalities were identified in almost two-thirds of the transmissions. The use of the Quebec Network resulted in the avoidance of transfers or clinic visits to university hospitals in seven-tenths of cases. We conclude that distance greater than 100 kilometres from a centre offering subspecialty services in paediatric cardiology is the most important criterion for choosing the peripheral centres that are most likely to use a telehealth network. In its first three years of operation, the telehealth network had a major impact on the delivery of paediatric cardiac care, improving access to subspecialty services across the province.