Definition: The short rib-polydactyly syndromes (SRPSs) are a group of lethal skeletal dysplasias with autosomal recessive inheritance characterized by markedly short ribs, short limbs, usually polydactyly, and multiple anomalies of major organs.

Short rib-polydactyly syndromes (SRPSs) are a descriptive category for a group of lethal skeletal dysplasias characterized by a hypoplastic thorax, short ribs, short limbs, polydactyly, and visceral abnormalities.

The 4 established variants are SRPS I (Saldino-Noonan type), SRPS II (Majewski type; MIM.263520), SRPS III (Verma-Naumoff type; MIM.263510), and SRPS IV (Beemer-Langer type; MIM.269860).

Type II (Majewski) short rib polydactyly can be distinguished from the Type I/III (Saldino-Noonan) type on the basis of radiographic and histologic changes.

All of the variants are thought to be inherited in an autosomal recessive pattern. Because of the frequent phenotypic overlap, however, there is controversy as to whether the variants are due to variable expression or to genetic heterogeneity. (12210298, 10517252, 8301649, 3981580)

Types

 SRPS1: Saldino-Noonan syndrome (MIM.265530)
 SRPS2: Majewski syndrome (MIM.263520)
 SRPS3: Verma-Naumoff syndrome (MIM.263510)
 SRPS4: Beemer-Langer syndrome (MIM.269860)
 Ellis-van Creveld disease (EVC1 and EVC2)
 unclassifiable short rib-polydactyly syndrome (17935248)

• short rib-polydactyly syndrome with acromesomelic hypomineralization and campomelia (17935248)

Synopsis

 short ribs
 short limbs
 polydactyly
 multiple anomalies of major organs (visceral anomalies)
 hypoplastic thorax
 chondral calcospherite (2080437)

Associations

 situs inversus (1481807, 1519646)
 persistent truncus arteriosus
 endocardial cushion defect
 hypoplastic lungs
 hypoplastic adrenal glands
 vaginal atresia
 polycystic pancreas in short-rib polydactyly syndrome type 3 (SRPS3) (Verma-Naumoff syndrome) (MIM.263510) (8172252)

 cerebral malformations

• multiple cyst formation in the parenchyma
• primary malformations of the nervous and mesenchymal tissues
• deposition of an unusual substance in the cerebral white matter
• capillary telangiectasia of the pia mater and choroid plexus
• olfactory dysplasia with asymmetry
• focal cortical dysplasia in the frontal lobe and cerebellum
• olivary dysplasia
• enlargement of the posterior part of the lateral ventricle
• neuronal migration disorders (16719409)

 renal anomalies

• bilateral renal agenesis (8543114)
• obstructive renal dysplasia (11746172)
• bilateral non-obstructive renal dysplasia (11746172)
• glomerulocystic kidney disease in short-rib polydactyly syndrome type II, Majewski type (SRPS2) (7491205, 8398663)
• bilateral non-obstructive renal dysplasia (BNORD) and polycystic pancreas in short-rib polydactyly syndrome type 3 (SRPS3) (Verma-Naumoff syndrome) (MIM.263510) (8172252)

 cystic hygroma (10064412)
 choroid plexus cysts (10064412)
 penile agenesis (7726223)
 cerebral malformations (8267012)

• anencephaly (8267012)

Cytogenetic anomalies

 pericentric inversion of chromosome 4 (7909650)
 17q paracentric inversion mosaicism (7856642)

Loci

 chromosome 4 (7909650)

• 4p16 (8054971)
• 4q13

Differential diagnosis

 all skeletal dysplasias with micromelia and short ribs

• thanatophoric dwarfism
• chondrodysplasia punctata
• osteogenesis imperfecta
• campomelic dysplasia
• oro-facial-digital syndrome type II (with Majewski type)

References

 Elcioglu NH, Hall CM. Diagnostic dilemmas in the short rib-polydactyly syndrome group. Am J Med Genet. 2002 Sep 1;111(4):392-400. PMID: 12210298

 Guschmann M, Horn D, Entezami M, Urban M, Hänel S, Kunze J, Vogel M. Mesomelic campomelia, polydactyly and Dandy-Walker cyst in siblings.Prenat Diagn. 2001 May;21(5):378-82. PMID: 11360278

 Sarafoglou K, Funai EF, Fefferman N, Zajac L, Geneiser N, Paidas MJ, Greco A, Wallerstein R.Short rib-polydactyly syndrome: more evidence of a continuous spectrum.Clin Genet. 1999 Aug;56(2):145-8. PMID: 10517252

 Lavanya R, Pratap K.Short rib polydactyly syndrome?a rare skeletal dysplasia.Int J Gynaecol Obstet. 1995 Sep;50(3):291-2. PMID: 8543114

 Martínez-Frías ML, Bermejo E, Urioste M, Huertas H, Arroyo I.Lethal short rib-polydactyly syndromes: further evidence for their overlapping in a continuous spectrum.J Med Genet. 1993 Nov;30(11):937-41. PMID: 8301649

 Martínez-Frías ML, Bermejo E, Urioste M, Egüés J, López Soler JA.Short rib-polydactyly syndrome (SRPS) with anencephaly and other central nervous system anomalies: a new type of SRPS or a more severe expression of a known SRPS entity? Am J Med Genet. 1993 Oct 1;47(5):782-7. PMID: 8267012

 Keating SJ, Eyre DR, Pritzker KP.Short rib polydactyly syndrome type I: an autopsy approach to diagnosis of chondrodysplasias.Mod Pathol. 1989 Sep;2(5):427-32. PMID: 2813343

 Erzen M, Stanescu R, Stanescu V, Maroteaux P.Comparative histopathology of the growth cartilage in short-rib polydactyly syndromes type I and type III and in chondroectodermal dysplasia.Ann Genet. 1988;31(3):144-50. PMID: 2464965

 Bernstein R, Isdale J, Pinto M, Du Toit Zaaijman J, Jenkins T.Short rib-polydactyly syndrome: a single or heterogeneous entity? A re-evaluation prompted by four new cases.J Med Genet. 1985 Feb;22(1):46-53. PMID: 3981580