Testing for osteogenesis imperfecta in cases of suspected non-accidental injury.

To evaluate if laboratory testing for osteogenesis imperfecta (OI) identifies children unrecognised by clinical examination in instances where non-accidental injury (NAI) is suspected as the likely cause of fracture, we carried out a retrospective review of available medical records and biochemical test results from 262 patients. Cultured fibroblasts were received for biochemical testing for OI from children in whom the diagnosis of NAI was suspected. Eleven of the samples had alterations in the amount or structure of type I collagen synthesised, consistent with the diagnosis of OI, and in 11 others we could not exclude OI. Referring physicians correctly identified children with OI in six of the 11 instances established by biochemical studies, did not identify OI by clinical examination in three, and there was inadequate clinical information to know in two others. Biochemical testing was inconclusive in 11 infants in whom the diagnosis of OI could not be excluded, none of whom were thought to be affected by the referring clinicians. Four children believed to have OI by clinical examination had normal biochemical studies, a false positive clinical diagnosis attributed, in large part, to the use of scleral hue (a feature that is age dependent) as a major diagnostic criterion. Given the inability to identify all children with OI by clinical examination in situations of suspected NAI, laboratory testing for OI (and other genetic predispositions for fractures) is a valuable adjunct in discerning the basis for fractures and may identify a small group of children with previously undiagnosed OI.

Osteogenesis imperfecta: mode of delivery and neonatal outcome.

OBJECTIVE: To evaluate the pregnancy characteristics, methods of delivery, and neonatal outcomes of fetuses affected by osteogenesis imperfecta. METHODS: We reviewed medical records of 1016 individuals whose cells were sent to the University of Washington Collagen Diagnostic Laboratory between 1987 and 1994 for confirmation of diagnoses of osteogenesis imperfecta. Information and neonatal records were available for 167 of those pregnancies. From those we identified method(s) of prenatal detection, delivery method, and neonatal complications, including survival and acquisition of new fractures, and related them to type of delivery. RESULTS: The cesarean delivery rate was 54%, most of them (53%) for nonvertex presentation and fewer than 15% because of an antenatal diagnoses of osteogenesis imperfecta. There was an unusually high rate of breech presentation at term (37%). In infants with nonlethal forms of osteogenesis imperfecta, 24 of 59 (40%) delivered by cesarean and 17 of 53 (32%) delivered vaginally had new fractures (chi(2) =.89; P =.3). Among 55 infants with the most severe form, 24 of 31 delivered by cesarean and 21 of 24 delivered vaginally died within 2 weeks of birth. CONCLUSION: Cesarean delivery did not decrease fracture rates at birth in infants with nonlethal forms of osteogenesis imperfecta nor did it prolong survival for those with lethal forms. Prenatal diagnosis did not influence mode of delivery in most instances. Most cesarean deliveries were done for usual obstetric indications.

Cerebrovascular complications in Ehlers-Danlos syndrome type IV.

Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant disorder that results from mutations in the COL3A1 gene, which encodes chains of type III procollagen. Individuals with this disorder are predisposed to rupture of arteries, the bowel, and the gravid uterus. To assess the frequency of central nervous system complications, we reviewed clinical data concerning 202 individuals with EDS type IV from 121 families in which the diagnosis was confirmed by biochemical or molecular studies. We identified 19 individuals with cerebrovascular complications, which included intracranial aneurysms with secondary hemorrhage, spontaneous carotid-cavernous sinus fistula, and cercical artery dissection. The mean age at presentation with these events was 28.3 years (range, 17-48 years). Although uncommon, EDS type IV is an important potential cause of stroke in young people. The disorder is readily identifiable clinically and the diagnosis has important implications for acute and long-term management and, potentially, for other family members. Because conventional angiography may exacerbate severe complications, noninvasive procedures such as Doppler and magnetic resonance angiography are the investigations of choice. Anticoagulation therapy may result in increased bruising or bleeding and should be used with caution.

Reevaluation of Russell-Silver syndrome.

Russell-Silver syndrome was reevaluated 2.9 to 13.0 years after initial diagnosis in 15 patients. At follow-up, five of the 15 patients exhibited late catch-up growth and had normal height, six had developmental delays or mental retardation, and asymmetry was present in five. Given the great variability in the long-term prognosis for growth and development in patients with Russell-Silver syndrome, there is a need to reevaluate this syndrome and its clinical implications.

Arteriohepatic dysplasia: phenotypic features and family studies.

Arteriohepatic dysplasia (AHD) is a disorder characterized by intrahepatic cholestasis and peripheral pulmonary artery stenosis. We have reviewed the phenotypic features in the 56 previously reported cases and 7 persons from our institutions with AHD to summarize the type of cardiac, hepatic, facial, ocular and skeletal manifestations observed in this disorder. Family studies evaluating first-degree relatives of patients with AHD are compatible with an autosomal dominant mode of inheritance with reduced penetrance and variable expressivity.