P2.K212: A Rare Cause of Short-Rib Thoracic Dysplasia in a Neonate

Introduction: Shwachman Diamond Syndrome (SDS) is a multisystem disorder that typically presents in early childhood with exocrine pancreatic dysfunction, bone marrow failure, and skeletal abnormalities. Neonatal diagnosis presents a challenging scenario due to its rare presentation. This case report aims to describe a neonate with thoracic dystrophy and pancytopenia found to have SDS.

Case Description: The patient is a full term SGA female neonate born via repeat C-section. Her mother received full prenatal care and had an uncomplicated pregnancy. At birth her physical exam was notable for bossing parietal bones, micrognathia, and rhizomelia of the extremities. A skeletal survey showed a small bell shaped rib cage and dysplasia of the pelvis and extremities. Quickly after delivery she required intubation for respiratory insufficiency.

During her hospital course, the patient had multi-organ complications. She had severe restrictive lung disease and concurrent pulmonary hypertension requiring invasive ventilation, nitric oxide, and sildenafil treatment. She had difficulty with feeding tolerance characterized by bilious emesis on small volume feeds without evidence of anatomic or functional obstruction. She had refractory anemia, thrombocytopenia, and neutropenia requiring numerous transfusions, G-CSF, and romiplostim with minimal improvement in blood counts. Genetic, hematologic, and infectious workup was sent. Her whole genome sequence showed unique mutations in both copies of the SBDS gene consistent with SDS. Both parents were found to be heterozygous carriers. After diagnosis was established, a fecal elastase was sent and found to be low.

Despite optimized care, the patient continued to have significant respiratory failure and pancytopenia. The family was extensively counseled and ultimately pursued comfort care. Compassionate extubation was performed with subsequent demise at 9 weeks of age.

Discussion: SDS is a disorder characterized by mutations in the SBDS gene on chromosome 7q11 which encodes for ribosomal proteins. The differential for primary short-rib thoracic dysplasias includes asphyxiating thoracic dystrophy (ATD or Jeune Syndrome), short-rib polydactyly syndrome, Ellis-van Creveld Syndrome, and Mainzer-Saldino Syndrome.

In contrast to primary skeletal dysplasias, SDS is a multisystem condition. It is the second most common cause of exocrine pancreatic insufficiency after cystic fibrosis. The spectrum of bone marrow abnormalities includes anemia, thrombocytopenia, and neutropenia. Skeletal abnormalities primarily include the metaphyses, and short-rib thoracic dysplasia is rare. Treatment is supportive and includes supplementation of pancreatic enzymes and fat soluble vitamins, transfusion of blood products, and bone marrow stimulating agents. Complications from both the disease and treatments are common.

Conclusion: This case highlights the importance of considering SDS in neonates with short-rib thoracic dysplasia. While many conditions in the differential are mainly skeletal disorders, SDS has multisystem involvement that can be life-threatening if not caught early. A high index of suspicion is necessary to recognize this condition in the neonatal population.