Shwachman-Diamond syndrome: a complex case demonstrating the potential for misdiagnosis as asphyxiating thoracic dystrophy (Jeune syndrome)

Abstract

BackgroundThe differential diagnosis of a neonate or fetus presenting with a bell-shaped or long narrow thorax includes a wide range of bony dysplasia syndromes. Where this is accompanied by respiratory distress, asphyxiating thoracic dystrophy (ATD, Jeune syndrome) is an important potential diagnosis. Shwachman-Diamond syndrome (SDS) is widely recognised as a cause of exocrine pancreatic dysfunction, short stature and bone marrow failure. It is not so well appreciated that rib and/or thoracic cage abnormalities occur in 30–50% of patients and that, in severe cases, these abnormalities may lead to thoracic dystrophy and respiratory failure in the newborn. There are, however, at least three previous case reports of children who were initially diagnosed with ATD who were subsequently shown to have SDS.Case presentationThis report details the case history of a patient misdiagnosed as having ATD as a neonate following the neonatal asphyxial death of her brother. She subsequently developed progressive pancytopenia but was only diagnosed with SDS at 11 years of age after referral for haematopoietic stem cell transplantation for bone marrow failure accompanied by trilineage dysplasia and clonal cytogenetic abnormalities on bone marrow examination. Subsequent testing revealed the presence of fat globules in stools, reduced faecal chymotrypsin, fat-soluble vitamin deficiency, metaphyseal dysplasia on skeletal survey and heterozygous mutations of the SBDS gene.ConclusionThis report highlights the potential for diagnostic confusion between ATD and SDS. It is important to include SDS in the differential diagnosis of newborns with thoracic dystrophy and to seek expert clinical and radiological assessment of such children.

Novel myopathy in a newborn with Shwachman–Diamond syndrome and review of neonatal presentation

“…In addition, the risk of misdiagnosis is high, as the differential diagnosis of a narrow thorax includes a wide range of bony dysplasias. Asphyxiating thoracic dystrophy (ATD or Jeune syndrome) is a possible misdiagnosis [Keogh et al, ; Schaballie et al, ; Saito‐Benz et al, ]. Among other differential diagnoses were paternal uniparental disomy 14 (UPD14), Ellis van Creveld syndrome, cranioectodermal dysplasia (CED or Sensenbrenner syndrome type 1–4) and cartilage‐hair hypoplasia (CHH).…”

“…The authors referred to the SDS syndrome described by both Shwachman and Bodian [Bodian et al, ; Shwachman et al, ]. Recent reports [Keogh et al, ; Schaballie et al, ] highlighted the risk of misdiagnosing an SDS‐related severe thoracic dystrophy as ATD. The authors explained that due to better intensive care, survival improved and the diagnosis of SDS becomes evident later, when the extraskeletal manifestations arise in the form of pancreatic insufficiency, hepatic fibrosis, hematological complications, and chronic renal failure.…”

Jeune Syndrome: Case Series Report

“…Патоморфологически обнару-живаются кистозные изменения и фиброз. Следует отме-тить, что при этом клинические проявления чаще всего не регистрируются [34].…”

Thoracic Hypoplasia at Birth as Presenting Feature of Shwachman-Diamond Syndrome in Twins

“…The differential diagnosis of a neonate with thoracic hypoplasia includes a range of rare syndromes: (ATD, Ellis-van Creveld syndrome, short rib-polydactyly syndrome (type I-IV), thoracolaryngopelvic dysplasia (Barnes syndrome), and SDS. 4 Although ATD is an important potential diagnosis in case of neonatal respiratory distress and thoracic hypoplasia, there are some cases in literature that report ATD misdiagnosis in children later diagnosed as SDS. [4][5][6][7][8] SDS is a rare autosomal recessive disorder first described in 1964; it is a multisystem disease involving bone marrow, pancreas, bony skeleton, and other organs such as liver, kidneys, teeth, brain, immune system; and is also associated with myelodysplastic syndrome and leukemia.…”

“…4 Although ATD is an important potential diagnosis in case of neonatal respiratory distress and thoracic hypoplasia, there are some cases in literature that report ATD misdiagnosis in children later diagnosed as SDS. [4][5][6][7][8] SDS is a rare autosomal recessive disorder first described in 1964; it is a multisystem disease involving bone marrow, pancreas, bony skeleton, and other organs such as liver, kidneys, teeth, brain, immune system; and is also associated with myelodysplastic syndrome and leukemia. 2,9 It is caused by mutations in the gene encoding Shwachman-Bodian-Diamond syndrome protein (SBDS), which is involved in several pathways that deal with ribosomal RNA metabolism, apoptosis, and mitotic spindle stabilization.…”