Rhizomelic chondrodysplasia punctata (RCP) is a rare autosomal recessive disorder with many associated medical complications. Prior to this study, natural history information about RCP was limited and based on experiences with small populations of affected individuals. We delineate the natural history of RCP through systematic analysis of 35 previously unreported individuals (as well as review of 62 literature cases with respect to survival and cause of death). Survival, growth, and developmental expectations and medical needs are summarized based upon experience with this population. Survival is greater among this population than previously reported, with 90% surviving up to 1 year and 50% surviving up to 6 years. Cause of death is most often respiratory problem. All infants with RCP have joint contractures, bilateral cataracts, and severe growth and psychomotor delays. Recommendations for health supervision of children with RCP and for parental counseling are presented. ß 2003 Wiley-Liss, Inc.KEY WORDS: bone dysplasia; osteochondrodysplasia; peroxisomal disorders; anticipatory care; guidelines for care INTRODUCTIONRhizomelic chondrodysplasia punctata (RCP) is a rare autosomal recessive disorder of peroxisome metabolism previously said to be inevitably lethal in infancy [Spranger et al., 1971;Heselson et al., 1978, Heymans et al., 1985. It is a panethnic disorder that affects about 1 in 100,000 individuals [Stoll et al., 1989]. As first described by Spranger et al. [1971], the clinical diagnostic characteristics of RCP include severe and symmetrical shortening of the proximal long bones (rhizomelia), bilateral cataracts, and severe growth and psychomotor delays. In addition to rhizomelia, clinical evidence of congenital contractures and typical dysmorphic facial characteristics and radiographic evidence of stippled epiphyses and vertebral coronal clefts can also be diagnostic.Biochemical analyses and complementation studies allow division of individuals with RCP into three types. Those with homozygous or compound heterozygous mutations in the PEX7 gene that encodes peroxin 7 comprise the largest group, classical RCP type 1 [Braverman et al., 1997;Motley et al., 1997;Purdue et al., 1997]. The spectrum of PEX7 mutations has been studied, and functional analysis of mutations demonstrates a direct correlation between PEX7allele activity and the severity of RCP [Motley et al., 2002]. RCP type 2 arises secondary to mutations in the acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) gene [Thai et al., 1997;Ofman et al., 1998], and RCP type 3 from mutations in the alkyl-dihydroxyacetonephosphate synthase (ADAPS) gene [Wanders et al., 1994;de Vet et al., 1998].Until Wardinsky et al. [1990] reported five new cases and reviewed 21 literature cases, no one had attempted to delineate the natural history of RCP. Little has subsequently appeared concerning the clinical course in RCP. This study systematically addresses health concerns that arise in infants and children with RCP. Its intent is to present evidence-base...

We describe a fifth instance of hypophosphatasia presenting with prenatal findings suggestive of a very severe bone dysplasia but with a subsequently benign course. Spontaneous improvement of long-bone angulation began prenatally. The postnatal course has been encouraging. This sixth clinical form of hypophosphatasia, which we suggest should be called the benign prenatal form of hypophosphatasia, should be added to the differential diagnostic possibilities considered when angulation or bowing of long bones is discovered prenatally.

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Newborn screening (NBS) protocols for cystic fibrosis (CF) are the first regional population-based programs to incorporate DNA analysis into their procedures. Research about these programs can inform policy and practice regarding how best to counsel families with abnormal NBS results. The grounded theory method guided interviews with 33 families whose infants had abnormal CF NBS results. A dimensional analysis of these interviews provided a theoretical framework describing parents' preferences regarding counseling during their infant's sweat test appointment. This framework describes the contexts and characteristics of the two main dimensions of parents' preferences: factual information and emotional support. Factual information included learning about the probability of a CF diagnosis, CF disease facts, sweat test procedure, and CF genetics. Social support consisted of offering parents a choice about the timing and amount of CF information, showing empathy for their distress, instilling hope, personalizing counseling, and providing hospitality. This framework also explains the consequences of counseling that matched versus mismatched parental preferences in these domains. Counseling that matched parents preferences reduced parents' distress while mismatched counseling tended to increase parents' worry about their infant.

This study examined the utility of array-based comparative genomic hybridization (aCGH) in detecting genetic abnormalities associated with late pregnancy loss. Comparisons were made with classic cytogenetics to test whether aCGH represents a superior methodology for the clinical evaluation of stillbirth. Stillborn infants were selected for aCGH testing from the Wisconsin Stillbirth Service Program (WiSSP) database and tissue bank, based on abnormal clinical findings (presence of at least two abnormalities of two different organs or parts of the body). aCGH analysis was successfully completed in 15 cases which met the clinical criteria and for which sufficient amount of high quality DNA was recovered from archival material. The testing was performed using commercially available 1 Mb BAC arrays. Among 15 tested stillborns, aCGH detected two abnormalities (trisomy 21 and an unbalanced translocation between chromosomes 3 and 10), for an overall detection rate of 13% in stillborns with malformations who had normal or unobtainable cytogenetic results. This preliminary study supports the clinical value of aCGH testing in diagnostic evaluation of stillborns with congenital anomalies.