The short rib-polydactyly syndromes (SRPS) are a group of autosomal recessive lethal skeletal dysplasias characterized by markedly short ribs, short limbs, polydactyly, and multiple anomalies of major organs, including heart, intestines, genitalia, kidney, liver, and pancreas. Five types ... The short rib-polydactyly syndromes (SRPS) are a group of autosomal recessive lethal skeletal dysplasias characterized by markedly short ribs, short limbs, polydactyly, and multiple anomalies of major organs, including heart, intestines, genitalia, kidney, liver, and pancreas. Five types have been distinguished: SRPS I (Saldino-Noonan type; 263530), SRPS II (Majewski type; see 263520), SRPS III (Verma-Naumoff type), SRPS IV (Beemer-Langer type; 269860), and SRPS V (614091). Significant phenotypic overlap has been reported in these forms (summary by Elcioglu and Hall, 2002).
Naumoff et al. (1977) suggested that a third type of short rib-polydactyly syndrome exists. They described 3 cases dying perinatally of asphyxia due to thoracic narrowing and found 3 possibly identical cases in the literature. Their cases 1 ... Naumoff et al. (1977) suggested that a third type of short rib-polydactyly syndrome exists. They described 3 cases dying perinatally of asphyxia due to thoracic narrowing and found 3 possibly identical cases in the literature. Their cases 1 and 2 were brother and sister. The authors did not clearly enunciate the features distinguishing this from the other two forms of short rib-polydactyly syndrome. They suggested that the disorder reported by Verma et al. (1975) may be the same as that in their patient. Naumoff (1980) indicated that the most important distinguishing features of type III are to be found in the skull: the cranial base is short, the forehead is bulging, the nasal bridge is depressed, and the occiput is flat. Another difference is in the radiologic appearance of the long tubular bones which show a distinct corticomedullary demarcation, somewhat widened metaphyses, and marked longitudinal spurs. Yang et al. (1980) reported a case with previously undescribed cytoplasmic inclusion bodies that were PAS-positive and diastase-resistant. Cloacal developmental abnormalities, which are invariably present in patients with SRPS I, are rare (1 in 13 cases). Sillence (1980) suggested that the claimed differences between types II (263520) and III are probably due to variability and not to heterogeneity, a view in which Spranger (1981) concurred. Bernstein et al. (1985) presented 4 cases of short rib-polydactyly syndrome from 3 nonconsanguineous families. The findings were most consistent with type III. They raised the question of allelism of the 3 types, being particularly impressed with the phenotypic overlap of SRPS I and SRPS III. All 4 of their cases showed anomalous sexual development. In spite of testicular differentiation in all 4 and a 46,XY karyotype in the 2 on whom chromosome studies were done, 2 infants were phenotypically female and 2 had ambiguous genitalia. Wu et al. (1995) described a family in which 3 consecutive conceptions resulted in 4 infants with SRPS. One was a twin conception. The condition was identified in the second and third pregnancies by prenatal ultrasound studies. Flat face, hypoplastic thorax, short limbs and ribs, polydactyly, absence of penis, and death soon after birth were noted in the first affected male baby. The affected female twins had the same characteristics, though milder. The last male baby was also severely affected, suggesting that chromosomal sex may be a modifying factor. Wu et al. (1995) suggested that the first and fourth cases most resembled the Verma-Naumoff type, whereas the twins resembled the type described by Marec et al. (1973); see 263530. Meizner and Barnhard (1995) reported diagnosis of SRPS type III at 20 weeks' gestation during routine ultrasonographic screening in a 21-year-old Bedouin woman. Widened humeral metaphyses with marginal spurs, postaxial polydactyly and shortened ribs were features demonstrated by the bodies. Polycystic kidneys and pointed metaphyses characterize SRPS type I; cleft lip/palate, polycystic kidneys, and disproportionately short tibia characterize type II; and acromesomelia and congenital heart disease characterize the Ellis-van Creveld syndrome (225500)--all conditions with thoracic restriction and polydactyly. Ho et al. (2000) reported a family with 2 brothers affected with mild Jeune syndrome (ATD; 208500), and a stillborn, the product of a marriage between the paternal first cousin and a maternal aunt of the 2 boys, with SRPS type III. The authors suggested that these conditions are variants of a single disorder. They proposed that the intrafamilial variability may reflect the effects of modifying loci on gene expression.
Merrill et al. (2009) and Dagoneau et al. (2009) identified homozygosity or compound heterozygosity for missense or nonsense mutations in the DYNC2H1 gene (603297) in families segregating short rib-polydactyly type III. Dagoneau et al. (2009) also identified DYNC2H1 ... Merrill et al. (2009) and Dagoneau et al. (2009) identified homozygosity or compound heterozygosity for missense or nonsense mutations in the DYNC2H1 gene (603297) in families segregating short rib-polydactyly type III. Dagoneau et al. (2009) also identified DYNC2H1 mutations in 3 families with asphyxiating thoracic dystrophy (see 613091). The DYNC2H1 gene is a component of a cytoplasmic dynein complex and is directly involved in the generation and maintenance of cilia. Dagoneau et al. (2009) concluded that ATD and SRPS III are variants of a single disorder belonging to the ciliopathy group.