Short rib – polydactyly syndrome

Overview

Short rib–polydactyly syndrome (SRPS) is a group of rare, inherited skeletal dysplasias characterized by short ribs, narrow thoracic cavity, shortened limbs, and polydactyly (extra fingers or toes). It is a lethal form of skeletal dysplasia, typically evident before birth or in the neonatal period, often leading to respiratory insufficiency due to a small, constricted chest. SRPS is classified into several subtypes (Types I–IV), each with overlapping but distinct clinical and radiographic features. The condition follows an autosomal recessive inheritance pattern and is considered part of the ciliopathy spectrum—disorders caused by defects in the structure or function of primary cilia.

Causes

Short rib–polydactyly syndrome is caused by mutations in genes involved in the development and function of primary cilia, which are crucial for signal transduction during embryonic development. These mutations disrupt normal skeletal patterning and growth. Genes commonly implicated in different types of SRPS include:

• DYNC2H1

• WDR19

• IFT80

• NEK1

• TTC21B

SRPS is inherited in an autosomal recessive manner, meaning both copies of the defective gene must be inherited—one from each parent—for the syndrome to manifest. Carrier parents are typically asymptomatic but have a 25% chance of passing the condition to each child.

Symptoms

The clinical presentation of SRPS is severe and usually identified prenatally or at birth. The main features are skeletal, but other organ systems may also be affected. Common signs and symptoms include:

Skeletal Features:

• Short, horizontal ribs leading to a narrow thoracic cavity

• Marked shortening of the limbs (micromelia)

• Polydactyly (extra digits on hands and/or feet)

• Bowed or abnormal long bones

• Pelvic anomalies

• Abnormal vertebrae or spine curvature

Thoracic and Respiratory Issues:

• Small, constricted chest leading to underdeveloped lungs (pulmonary hypoplasia)

• Severe respiratory distress immediately after birth

Other Possible Anomalies:

• Cleft lip and/or palate

• Genitourinary malformations

• Cardiac defects

• Hepatic or renal anomalies (especially in SRPS Type IV)

In most cases, the respiratory complications due to thoracic hypoplasia are life-threatening, resulting in perinatal death.

Diagnosis

SRPS can be suspected based on prenatal ultrasound findings and confirmed postnatally through clinical examination, radiographic imaging, and genetic testing. Diagnostic approaches include:

• Prenatal ultrasound: Can detect short limbs, narrow chest, polydactyly, and other skeletal anomalies as early as the second trimester

• Fetal MRI: May be used to further evaluate lung volume and organ anomalies

• Postnatal radiographs: Reveal characteristic skeletal abnormalities, such as short ribs, bowed long bones, and pelvic deformities

• Genetic testing: Confirms mutations in known SRPS-associated genes and can differentiate between subtypes

• Family history: Consanguinity or prior affected pregnancies may suggest a hereditary pattern

Treatment

There is no curative treatment for short rib–polydactyly syndrome. Management focuses on supportive care, but due to the severity of pulmonary hypoplasia and associated anomalies, the prognosis is typically poor. Treatment strategies may include:

Supportive and Palliative Care:

• Respiratory support (e.g., mechanical ventilation) may be attempted, though often ineffective in severe cases

• Palliative care consultations to provide comfort and family support

• Psychological and genetic counseling for parents

Prenatal Counseling:

• For families with a known genetic mutation, prenatal testing via chorionic villus sampling (CVS) or amniocentesis can be offered

• In vitro fertilization with preimplantation genetic diagnosis (PGD) may be considered for future pregnancies

Prognosis

The prognosis of short rib–polydactyly syndrome is generally very poor. Most affected infants die in utero or shortly after birth due to severe respiratory failure caused by underdeveloped lungs and thoracic cavity. Survivability is extremely rare and, when it occurs, is usually associated with milder variants or incomplete forms of the syndrome.

For families affected by SRPS, genetic counseling is essential for understanding recurrence risks and exploring reproductive options. Advances in genetic testing and prenatal imaging have improved the ability to diagnose SRPS early in pregnancy, enabling informed decision-making and early intervention planning where applicable.