Shwachman-Diamond Syndrome Clinical Presentation

Updated: Sep 09, 2022
  • Author: Antoinette C Spoto-Cannons, MD, FAAP; Chief Editor: Hassan M Yaish, MD  more...
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  • Patients with Shwachman-Diamond syndrome (SDS) typically present with diarrhea, short stature, weight loss, and dry skin (eczema).

    • They may have fatty stools that usually improve with age. [43]

    • Imperforate anus and Hirschsprung disease have been associated with Shwachman-Diamond syndrome. These associations may delay diagnosis of Shwachman-Diamond syndrome because the presenting symptom is constipation and not diarrhea.

  • Recurrent bacterial infections of the upper respiratory tract, otitis media, sinusitis, pneumonia, osteomyelitis, bacteremia, skin infections, aphthous stomatitis, fungal dermatitis, and paronychia are common because of a neutropenia/neutrophil migration defect. [5, 6, 7, 8]

  • Hearing loss may occur secondary to recurrent otitis media.

  • A history of pallor, easy bruising, epistaxis, melena, hematemesis, or hematuria may be present in individuals with Shwachman-Diamond syndrome.

  • Unlike patients with cystic fibrosis, patients with Shwachman-Diamond syndrome have a paucity of pulmonary symptoms, [44] although some patients may present with recurrent upper and lower respiratory tract infections.

  • Delayed dental development, gingival bleeding upon brushing, and pain with eating (associated with recurrent oral ulcerations) may occur. [45]

  • Saliva production is decreased; however, no significant clinical symptoms are associated with this phenomenon.

  • Patients with Shwachman-Diamond syndrome typically experience delayed puberty. [10]

  • Mild-to-moderate psychomotor and/or developmental delay including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders may be observed in as many as 15% of affected individuals and has been shown to affect quality of life. [24]



See the list below:

  • Patients with Shwachman-Diamond syndrome may appear emaciated, with abdominal distension accentuated by hypotonia and hepatomegaly.

  • More than 50% of these individuals have short stature with a normal growth velocity. [8] Their height and weight are usually below the third percentile but may occasionally reach the 25th percentile. [10]

  • In addition to short stature, skeletal abnormalities in an individual with Shwachman-Diamond syndrome may include the following:

    • Clinodactyly

    • Syndactyly

    • Supernumerary metatarsals

    • Coxa vara deformity

    • Genu and cubitus valgus

    • Tooth enamel defects (dental dysplasia), including hypomaturation, hypocalcification, and hypoplasia (Dental caries and tooth surface loss are seen in about a third of patients. [9] )

  • Dermatologic manifestations in a person with Shwachman-Diamond syndrome include the following:

    • Eczema

    • Ichthyosis

    • Petechiae



Shwachman-Diamond syndrome is inherited in an autosomal recessive fashion. [46] See the image below.

Autosomal recessive inheritance. Autosomal recessive inheritance.

In 90% of patients with Shwachman-Diamond syndrome, mutations have been found in the SBDS gene located on chromosome 7q11. The most frequent mutations are due to gene conversion between the SBDS gene and its pseudogene (SBDSP). The SBDS gene contains 5 exons, which encode a 250-amino-acid protein of unknown function. [47] SBDS is a highly conserved protein [48] which is known to play a role in ribosome biosynthesis, mitotic spindle assembly, chemotaxis, and regulation of reactive oxygen species generation. [49, 50, 51, 52, 53]

Experiments reveal that SBDS knockdown affects expression of critical genes involved in brain development and function, bone morphogenesis, blood cell proliferation and differentiation, and cell adhesion. [54] This may be due to its role in ribosome biogenesis or RNA processing, which has been shown in yeast [55] and mammalian cells. [56] One of the SBDS-binding proteins, nucleophosmin (NPM, B23), has a role in ribosome biogenesis and control of cell cycle, [57] and the SBDS proteins facilitate the release of eIF-6 which impairs the association of the 40S and 60S subunits. [51] Interestingly, mutations that affect ribosome assembly or function are associated with other inherited bone marrow failure syndromes, [58] and models of how impairment of ribosomal pathways might affect hematopoiesis and tumorigenesis are currently under investigation. [57]

Burwick et al found that knockdown of eIF-6 expression showed improvement of ribosomal subunit association but did not improve the hematopoietic deficits noted in Shwachman-Diamond syndrome. [59]

A study by Joyce et al indicated that in Shwachman-Diamond syndrome, increased activity in the transforming growth factor-β (TGFβ) pathway triggers hematopoietic dysfunction and bone marrow failure. The investigators found a rise in hematopoietic stem cells and multipotent progenitors in Shwachman-Diamond syndrome patient bone marrow in connection with TGFβ inhibitors. The study also reported higher levels of TGFβ pathway members in the blood plasma of patients with the syndrome. [60]