Short rib-polydactyly syndrome

Short rib-polydactyly syndrome (SRPS) is a group of lethal autosomal recessive skeletal dysplasias characterized by severely shortened ribs, short limbs (micromelia), polydactyly (extra fingers and/or toes), and multiple organ abnormalities. Historically, four subtypes have been described: type I (Saldino-Noonan), type II (Majewski), type III (Verma-Naumoff), and type IV (Beemer-Langer). These conditions are now understood to represent a phenotypic spectrum of ciliopathies caused by mutations in genes involved in intraflagellar transport and cilia function, including DYNC2H1, WDR35, WDR60, IFT80, IFT172, NEK1, and others. The syndromes overlap significantly with the broader group of short-rib thoracic dysplasias (also known as asphyxiating thoracic dystrophy or Jeune syndrome), though SRPS types are generally considered the most severe, lethal end of this spectrum. The hallmark feature is a markedly narrow, constricted thorax due to extremely short ribs, which leads to severe pulmonary hypoplasia (underdeveloped lungs) and respiratory insufficiency. This is the primary cause of death, which typically occurs in the prenatal period or shortly after birth. Additional features may include hydrops fetalis, cardiovascular malformations (such as transposition of the great vessels or septal defects), gastrointestinal anomalies (including intestinal malrotation and anal atresia), genitourinary malformations (renal cystic dysplasia, ambiguous genitalia), and central nervous system abnormalities (such as Dandy-Walker malformation or other posterior fossa defects). The long bones are markedly shortened with metaphyseal irregularities, and the pelvis often shows characteristic radiographic changes. Diagnosis is typically made prenatally via ultrasound showing a narrow thorax, short limbs, and polydactyly, and can be confirmed by molecular genetic testing. The condition is almost invariably lethal in the perinatal period, and there are currently no curative treatments. Management is supportive and palliative, and genetic counseling is essential for affected families given the 25% recurrence risk in subsequent pregnancies. Prenatal molecular diagnosis is available for families with known pathogenic variants.

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