Clinical insights gained from eight new cases and review of reported cases with Jeune syndrome (asphyxiating thoracic dystrophy)

Abstract

Jeune syndrome, originally described as asphyxiating thoracic dystrophy by Jeune et al. [Jeune et al. (1955); Arch Fr Pediatr 12:886-891], is an autosomal recessive osteochondrodysplasia with characteristic skeletal abnormalities, and variable renal, hepatic, pancreatic, and retinal complications. We present eight patients, including two brothers with Jeune syndrome, and an extensive review of 118 cases in the published literature with the purposes of: (1) defining the clinical and radiological diagnostic criteria for Jeune syndrome; (2) comparing our cases to those in the literature meeting the documented clinical and radiological findings of Jeune syndrome, in order to: (3) provide an accurate clinical characterization of Jeune syndrome with frequency of associated complications and outcome data. In order to estimate the frequency of phenotypic abnormalities in Jeune syndrome as precisely as possible, we did not include reports in the literature with incomplete descriptions of the radiologic and clinical findings, nor those reports having additional findings overlapping with other syndromes. We found that the occurrence of renal, hepatic, and ophthalmologic complications is variable; does not correlate with severity of the skeletal phenotype; nor is it predictable even with the presence of a well-defined skeletal phenotype, as in this study. Based upon these cases with Jeune syndrome, renal and hepatic abnormalities occur in approximately 30% of cases, with renal failure occurring in 38% of those with kidney involvement. Eye abnormalities are reported in 15%, but it is unclear whether this represents under-ascertainment. There is a 1.2:1 ratio between living and deceased patients; a respiratory cause of death is most common, occurring almost exclusively in those less than 2 years of age, and a renal etiology accounts for all deaths between the ages of 3-10 years of age. There is a paucity of affected individuals reported in the literature greater than age 20 years, and a lack of longitudinal data to obtain accurate data on morbidity and mortality of Jeune syndrome at older ages. This study provides a well-defined group of patients with Jeune syndrome with delineation of the frequency of associated findings, which may form a basis for current and future genotype-phenotype studies.

Sensenbrenner syndrome (Cranioectodermal dysplasia): Clinical and molecular analyses of 39 patients including two new patients

“…Sensenbrenner patients with mutations were more likely to have sagittal craniosynostosis, joint laxity, dental anomalies, retinal abnormalities, and congenital heart defects. As expected, considerable overlap with ATD-JS was noted, but the distinctive Sensenbrenner facial appearance (dolichocephaly, high hairline, forehead bossing), sagittal craniosynostosis, ectodermal anomalies (teeth, hair, nails), and syndactyly appear to differentiate the two syndromes [Keppler-Noreuil et al, 2011;Baujat et al, 2013]. Severe forms of Sensenbrenner syndrome and ATD-JS have been diagnosed as short rib-polydactyly syndromes (SRPs).…”

“…Liver involvement was seen in approximately half of the Sensenbrenner patients, regardless of mutation status, similar to that in ATD-JS. Liver disease in ATD-JS, including most commonly hepatic fibrosis, is reported in 28% of patients compared to 40-50% of patients with Sensenbrenner syndrome, regardless of mutation status [Keppler-Noreuil et al, 2011;Baujat et al, 2013]. In comparison, liver involvement is a universal finding in patients with MKS and COACH syndrome (a subset of JSRD) with cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis [Gunay-Aygun, 2009].…”

“…There is some overlap with SaldinoMainzer syndrome since both have short (cone-shaped) phalanges, retinopathy, and renal disease [Perault et al, 2012]. To further illustrate the overlap, we propose that a patient reported as ATD-JS [patient 8, Keppler-Noreuil et al, 2011] be reassigned as Sensenbrenner syndrome based on the small teeth, sparse hair, "boxy" cranium, and facial appearance (Fig. 3).…”

“…Fourteen patients had echogenic kidneys detected on ultrasound study, of which three were noted to be enlarged. The frequency of renal complications in ATD-JS is reported as 17-30% with fewer than half with renal involvement developing renal failure compared to those with Sensenbrenner syndrome, regardless of mutation status ($70%) [Keppler-Noreuil et al, 2011;Baujat et al, 2013].…”

“…Similarly in ATD-JS, death occurred in 44% of reported patients with the majority ($60%) aged <5 years. Cause of death from ages birth to 2 years was almost exclusively respiratory, while cause of death between 3 and 10 years was primarily renal in origin [Keppler-Noreuil et al, 2011].…”