Shwachman–Bodian–Diamond syndrome: metaphyseal chondrodysplasia in children with pancreatic insufficiency and neutropenia

Abstract

Shwachman-Bodian-Diamond syndrome (OMIM 260400) was identified in 1964 by pediatricians Harry Shwachman, a leader in cystic fibrosis, and Louis K. Diamond, a hematologist, along with pediatrician and morbid anatomist Martin Bodian. Initially the syndrome's clinical presentation included exocrine pancreatic insufficiency (lipomatous replacement of the pancreas) and neutropenia. In 1967 skeletal changes of metaphyseal chondrodysplasia were also described, completing the triad of findings; these abnormalities are present in all affected children and should be viewed as an integral feature of the syndrome, also called Shwachman-Diamond syndrome.

Further evidence for the involvement of EFL1 in a Shwachman–Diamond-like syndrome and expansion of the phenotypic features

“…Shwachman–Diamond syndrome (SDS; OMIM 260400) is an autosomal recessive condition that is characterized by a triad of exocrine pancreatic insufficiency, bone marrow dysfunction, and metaphyseal dysostosis ( Bodian et al 1964 ; Shwachman et al 1964 ; Burke et al 1967 ). Most patients present as infants with growth failure due to pancreatic insufficiency and/or recurrent infections due to neutropenia ( Dror et al 2011 ), whereas the metaphyseal changes leading to short stature typically become evident in childhood or later ( Levin et al 2015 ). The pancreatic dysfunction varies in severity, and a subset of patients may show improvement in pancreatic function in late childhood ( Ginzberg et al 1999 ).…”

“…Neutropenia and anemia are the most common bone marrow abnormalities, but thrombocytopenia and pancytopenia may also be seen ( Dror et al 2011 ). Metaphyseal chondrodysplasia seen in SDS is present in all patients but shows variability, even within the same family ( Levin et al 2015 ). Skeletal findings are typically symmetrical and are more severe in the lower limbs.…”

“…Skeletal findings are typically symmetrical and are more severe in the lower limbs. By age 2 yr, metaphyseal changes seen include broadening of the metaphyses with characteristic lucent and sclerotic changes, which disappear when the physes fuse at puberty ( Levin et al 2015 ).…”

Biallelic splicing variants in the nucleolar 60S assembly factor RBM28 cause the ribosomopathy ANE syndrome

“…Though not fully understood, tissue-specific defects are the hallmark of ribosomopathies (11,17). Tissues formed from hematopoietic or neural crest cell lineages are disproportionately affected, resulting in anemia, neutropenia, and leukemia, bone marrow failure diseases including Diamond-Blackfan Anemia (DBA) (18)(19)(20)(21)(22)(23) and Shwachman-Diamond syndrome (24)(25)(26), craniofacial, dermatological, and neurological diseases including Treacher Collins syndrome (27)(28)(29) and postaxial acrofacial dysostosis (30), and alopecia, neurologic defects, and endocrinopathy (ANE) syndrome (31)(32)(33)(34).…”

Short stature: an ordinary sign for an unordinary diagnosis

“…The metaphyseal changes lead to asymmetrical metaphyseal growth and deformity. Moreover, generalized disturbance in bone metabolism, as well as delayed appearance of secondary ossification centers, has been shown in SDS; these symptoms cause bone age delay and abnormal bone turnover, with decreased activity of both osteoclasts and osteoblasts [ 12 , 13 ]. In conformity with these data, the bone age of the patient showed a severe ossification delay.…”