Short rib - polydactyly syndrome
Short rib - polydactyly syndrome is a group of genetic disorders characterized by reduced-size thoracic rib cage; shortened ribs and long tubular bones; and malformation of the cupping mechanism in the hip where the femur rotates with movement. SRPS are deadly disorders.
Definition & Facts
As of 2013, peer-reviewed studies described four types of short rib-polydactyly syndromes: Saldino-Noonan syndrome, Majewski syndrome, Verma-Naumoff syndrome, Beemer-Langer syndrome. As of 2014, OMIM, an encyclopedia of genetic disorders affiliated with Johns Hopkins University, categorized short rib - polydactyly syndromes under the umbrella of short-rib thoracic dysplasias. Incidence data reveal that SRPS is rare.
Symptoms & Complaints
All short rib - polydactyly syndromes are caused by autosomal recessive inheritance patterns. Short rib – polydactyly syndromes are congenital disorders, sharing a common genetic anomaly that causes ciliopathy, which is a broad range of disorders.
Heterozygous mutations appear related to genetic damage in production of proteins and resulting problems in ciliogenesis. Effects on the inability of the GLI2 transcription factor to operate properly within the primary cilium appear to disrupt cell division, causing malformation in divided cells. The WDR60 gene appears to be the locus for the cellular miscoding. Gene WDR35 mediates cilia generation and maintenance.
Diagnosis & Tests
Medical ultrasounds are routine in prenatal care in many parts of the world. If medical imaging is performed, reduction in rib case dimensions, anomalies in ribs and long bones, and extra fingers and toes may be determined during prenatal diagnosis. Abnormal images suggest further evaluation with magnetic resonance imaging (MRI), or computed tomography (CT) scans and fetal chemistry studies to differentiate disorders and provide prenatal diagnoses and after-birth management planning. Fetal blood tests may be required to assess whether or not there is organ failure, and if so, to what extent.
Half of positive sonographic atypical scans are readily recognized by clinicians. For others, child and parent DNA assessment using molecular analysis may be recommended when scans are abnormal, particularly when previous children have identified autosomal dominant bone problems.
Assessment at birth (newborn screening) will detail specific anomalies, e.g., compromised heart, pulmonary dysfunction, liver disease, and kidney disease. Lab data will determine the extent of genetic involvement and suggest appropriate management.
Whether children with these syndromes survive or die in the womb or shortly after birth, all should have diagnoses confirmed (in the latter case, through fetal autopsy). Data may be helpful in determining baby-mother care in subsequent pregnancies or in pregnancies of other family members.
Treatment & Therapy
Depending on the symptoms, fetal surgery versus surgery after birth may be planned. If all identification of degree of anomaly has taken place before conception or early in the pregnancy, genome editing using CRISPR or subsequent technology may be appropriate for the child, particularly very early in the pregnancy.
Prevention & Prophylaxis
Early diagnosis during pregnancy can help parents prepare for having the child; for instance, treatment for bone fractures and pulmonary support may be prepared for the child after birth. Early diagnosis may help the parents make necessary accommodations such as deciding between a vaginal delivery versus a caesarean section.
The mother’s organ and bone status may also affect how the child will be delivered. In terms of the child, delivery, and support system, home planning may be determined once the child’s known status during gestation is determined.