U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Shwachman-Diamond syndrome 1(SDS1)

MedGen UID:
1640046
Concept ID:
C4692625
Disease or Syndrome
Synonym: SDS1
 
Genes (locations): DNAJC21 (5p13.2); SBDS (7q11.21); SRP54 (14q13.2)
 
Monarch Initiative: MONDO:0044204
OMIM®: 260400

Definition

Shwachman-Diamond syndrome (SDS) is characterized by: exocrine pancreatic dysfunction with malabsorption, malnutrition, and growth failure; hematologic abnormalities with single- or multilineage cytopenias and susceptibility to myelodysplasia syndrome (MDS) and acute myelogeneous leukemia (AML); and bone abnormalities. In almost all affected children, persistent or intermittent neutropenia is a common presenting finding, often before the diagnosis of SDS is made. Short stature and recurrent infections are common. [from GeneReviews]

Additional description

From MedlinePlus Genetics
Shwachman-Diamond syndrome is an inherited condition that affects many parts of the body, particularly the bone marrow, pancreas, and bones.

The major function of bone marrow is to produce new blood cells. These include red blood cells, which carry oxygen to the body's tissues; white blood cells, which fight infection; and platelets, which are blood cells that are necessary for normal blood clotting. In Shwachman-Diamond syndrome, the bone marrow malfunctions and does not make some or all types of white blood cells. A shortage of neutrophils, the most common type of white blood cell, causes a condition called neutropenia. Most people with Shwachman-Diamond syndrome have at least occasional episodes of neutropenia, which makes them more vulnerable to infections, often involving the lungs (pneumonia), ears (otitis media), or skin. Less commonly, bone marrow abnormalities lead to a shortage of red blood cells (anemia), which causes fatigue and weakness, or a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding.

People with Shwachman-Diamond syndrome have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS) and aplastic anemia, which are disorders caused by abnormal blood stem cells, and a cancer of blood-forming tissue known as acute myeloid leukemia (AML).

Shwachman-Diamond syndrome also affects the pancreas, which is an organ that plays an essential role in digestion. One of this organ's main functions is to produce enzymes that help break down and use nutrients from food. In most infants with Shwachman-Diamond syndrome, the pancreas does not produce enough of these enzymes. This condition is known as pancreatic insufficiency. Infants with pancreatic insufficiency have trouble digesting food and absorbing nutrients and vitamins that are needed for growth. As a result, they often have fatty, foul-smelling stools (steatorrhea); are slow to grow and gain weight (failure to thrive); and experience malnutrition. Pancreatic insufficiency often improves with age in people with Shwachman-Diamond syndrome.

Skeletal abnormalities are another common feature of Shwachman-Diamond syndrome. Many affected individuals have problems with bone formation and growth, most often affecting the hips and knees. Low bone density is also frequently associated with this condition. Some affected infants are born with a narrow rib cage and short ribs, which can cause life-threatening problems with breathing. The combination of skeletal abnormalities and slow growth results in short stature in most people with this disorder.

The complications of Shwachman-Diamond syndrome can affect several other parts of the body, including the liver, heart, endocrine system (which produces hormones), eyes, teeth, and skin. Additionally, studies suggest that Shwachman-Diamond syndrome may be associated with delayed speech and the delayed development of motor skills such as sitting, standing, and walking.  https://medlineplus.gov/genetics/condition/shwachman-diamond-syndrome

Clinical features

From HPO
Acute myeloid leukemia
MedGen UID:
9730
Concept ID:
C0023467
Neoplastic Process
A clonal expansion of myeloid blasts in the bone marrow, blood or other tissues. The classification of acute myeloid leukemias (AMLs) encompasses four major categories: 1) AML with recurrent genetic abnormalities; 2) AML with multilineage dysplasia; 3) Therapy-related AML; 4) AML not otherwise specified. The required bone marrow or peripheral blood blast percentage for the diagnosis of AML is 20% (WHO classification)
Myelodysplasia
MedGen UID:
10231
Concept ID:
C0026985
Congenital Abnormality
Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Coxa vara
MedGen UID:
1790477
Concept ID:
C5551440
Anatomical Abnormality
Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees.
Myocardial necrosis
MedGen UID:
254841
Concept ID:
C1442837
Disease or Syndrome
Irreversible damage to heart tissue (myocardium) due to lack of oxygen after a heart attack (myocardial infarction).
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Steatorrhea
MedGen UID:
20948
Concept ID:
C0038238
Finding
Greater than normal amounts of fat in the feces. This is a result of malabsorption of lipids in the small intestine and results in frothy foul-smelling fecal matter that floats.
Exocrine pancreatic insufficiency
MedGen UID:
75647
Concept ID:
C0267963
Disease or Syndrome
Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Specific learning disability
MedGen UID:
871302
Concept ID:
C4025790
Mental or Behavioral Dysfunction
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Persistence of hemoglobin F
MedGen UID:
68693
Concept ID:
C0239941
Finding
Hemoglobin F (HbF) contains two globin alpha chains and two globin gamma chains. It is the main form of hemoglobin in the fetus during the last seven months of intrauterine development and in the half year of postnatal life. In adults it normally makes up less than one percent of all hemoglobin. This term refers to an increase in HbF above this limit. In beta thalassemia major, it may represent over 90 percent of all hemoglobin, and in beta thalassemia minor it may make up between 0.5 to 4 percent.
Proximal femoral epiphysiolysis
MedGen UID:
57704
Concept ID:
C0149887
Disease or Syndrome
Slipped capital femoral epiphysis is defined as a posterior and inferior slippage of the proximal epiphysis of the femur onto the metaphysis (femoral neck), occurring through the physeal plate during the early adolescent growth spurt.
Metaphyseal chondrodysplasia
MedGen UID:
120528
Concept ID:
C0265290
Congenital Abnormality
An abnormality of skeletal development characterized by a disturbance of the metaphysis and its histological structure with relatively normal epiphyses and vertebrae.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Narrow greater sciatic notch
MedGen UID:
154353
Concept ID:
C0566888
Finding
A narrowing of the sacrosciatic notch, i.e., the deep indentation in the posterior border of the hip bone at the point of union of the ilium and ischium.
Proximal femoral metaphyseal irregularity
MedGen UID:
324485
Concept ID:
C1836320
Finding
Irregularity of the normally smooth surface of the proximal metaphysis of the femur.
Anterior rib cupping
MedGen UID:
337520
Concept ID:
C1846154
Finding
Wide, concave anterior rib end.
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Irregular ossification at anterior rib ends
MedGen UID:
376700
Concept ID:
C1850083
Finding
Ovoid vertebral bodies
MedGen UID:
344549
Concept ID:
C1855665
Finding
When viewed in lateral radiographs, vertebral bodies have a roughly rectangular configuration. This term applies if the vertebral body appears rounded or oval.
Enlargement of the costochondral junction
MedGen UID:
346535
Concept ID:
C1857180
Finding
Abnormally increased size of the costochondral junctions, which are located between the distal part of the ribs and the costal cartilages, which are bars of hyaline cartilage that connect the ribs to the sternum.
Metaphyseal sclerosis
MedGen UID:
765440
Concept ID:
C3552526
Finding
Abnormally increased density of metaphyseal bone.
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.

Professional guidelines

PubMed

Han X, Lu S, Gu C, Bian Z, Xie X, Qiao X
BMC Pediatr 2023 Oct 6;23(1):503. doi: 10.1186/s12887-023-04324-3. PMID: 37803383Free PMC Article
Touw IP
Curr Opin Hematol 2022 Jan 1;29(1):27-33. doi: 10.1097/MOH.0000000000000696. PMID: 34854832Free PMC Article
Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB
Orphanet J Rare Dis 2011 May 19;6:26. doi: 10.1186/1750-1172-6-26. PMID: 21595885Free PMC Article

Recent clinical studies

Etiology

Dokal I, Tummala H, Vulliamy T
Blood 2022 Aug 11;140(6):556-570. doi: 10.1182/blood.2020006481. PMID: 35605178Free PMC Article
Cesaro S, Pegoraro A, Sainati L, Lucidi V, Montemitro E, Corti P, Ramenghi U, Nasi C, Menna G, Zecca M, Danesino C, Nicolis E, Pasquali F, Perobelli S, Tridello G, Farruggia P, Cipolli M
J Pediatr 2020 Apr;219:196-201.e1. Epub 2020 Feb 6 doi: 10.1016/j.jpeds.2019.12.041. PMID: 32037152
Kallen ME, Dulau-Florea A, Wang W, Calvo KR
Semin Hematol 2019 Jan;56(1):69-82. Epub 2018 Jun 23 doi: 10.1053/j.seminhematol.2018.05.016. PMID: 30573048
Bezzerri V, Cipolli M
Mol Diagn Ther 2019 Apr;23(2):281-290. doi: 10.1007/s40291-018-0368-2. PMID: 30413969
Babushok DV, Bessler M
Best Pract Res Clin Haematol 2015 Mar;28(1):55-68. Epub 2014 Nov 12 doi: 10.1016/j.beha.2014.11.004. PMID: 25659730Free PMC Article

Diagnosis

Dokal I, Tummala H, Vulliamy T
Blood 2022 Aug 11;140(6):556-570. doi: 10.1182/blood.2020006481. PMID: 35605178Free PMC Article
Bezzerri V, Cipolli M
Mol Diagn Ther 2019 Apr;23(2):281-290. doi: 10.1007/s40291-018-0368-2. PMID: 30413969
West AH, Churpek JE
Hematology Am Soc Hematol Educ Program 2017 Dec 8;2017(1):79-87. doi: 10.1182/asheducation-2017.1.79. PMID: 29222240Free PMC Article
Babushok DV, Bessler M
Best Pract Res Clin Haematol 2015 Mar;28(1):55-68. Epub 2014 Nov 12 doi: 10.1016/j.beha.2014.11.004. PMID: 25659730Free PMC Article
Myers KC, Bolyard AA, Otto B, Wong TE, Jones AT, Harris RE, Davies SM, Dale DC, Shimamura A
J Pediatr 2014 Apr;164(4):866-70. Epub 2013 Dec 31 doi: 10.1016/j.jpeds.2013.11.039. PMID: 24388329Free PMC Article

Therapy

Meng X, Zhang H, Dong L, Min Q, Yu M, Li Y, Liu L, Wang W, Ying W, Sun J, Wang JY, Hou J, Wang X
Blood Adv 2024 Apr 9;8(7):1667-1682. doi: 10.1182/bloodadvances.2023012171. PMID: 38286463Free PMC Article
Thompson AS, Giri N, Gianferante DM, Jones K, Savage SA, Alter BP, McReynolds LJ
Pediatr Res 2022 Dec;92(6):1671-1680. Epub 2022 Mar 23 doi: 10.1038/s41390-022-02009-8. PMID: 35322185Free PMC Article
Bezzerri V, Api M, Allegri M, Fabrizzi B, Corey SJ, Cipolli M
Int J Mol Sci 2020 Jun 30;21(13) doi: 10.3390/ijms21134672. PMID: 32630050Free PMC Article
Babushok DV, Bessler M
Best Pract Res Clin Haematol 2015 Mar;28(1):55-68. Epub 2014 Nov 12 doi: 10.1016/j.beha.2014.11.004. PMID: 25659730Free PMC Article
Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB
Orphanet J Rare Dis 2011 May 19;6:26. doi: 10.1186/1750-1172-6-26. PMID: 21595885Free PMC Article

Prognosis

Hudda Z, Myers KC
Hematology Am Soc Hematol Educ Program 2023 Dec 8;2023(1):141-148. doi: 10.1182/hematology.2023000471. PMID: 38066882Free PMC Article
Cesaro S, Pegoraro A, Sainati L, Lucidi V, Montemitro E, Corti P, Ramenghi U, Nasi C, Menna G, Zecca M, Danesino C, Nicolis E, Pasquali F, Perobelli S, Tridello G, Farruggia P, Cipolli M
J Pediatr 2020 Apr;219:196-201.e1. Epub 2020 Feb 6 doi: 10.1016/j.jpeds.2019.12.041. PMID: 32037152
Garah J, Rosen I, Shaoul R
J Pediatr Gastroenterol Nutr 2019 Apr;68(4):574-577. doi: 10.1097/MPG.0000000000002267. PMID: 30633105
Dolezal JM, Dash AP, Prochownik EV
BMC Cancer 2018 Mar 12;18(1):275. doi: 10.1186/s12885-018-4178-z. PMID: 29530001Free PMC Article
Parikh S, Bessler M
Curr Opin Pediatr 2012 Feb;24(1):23-32. doi: 10.1097/MOP.0b013e32834eca77. PMID: 22227778Free PMC Article

Clinical prediction guides

Thompson AS, Giri N, Gianferante DM, Jones K, Savage SA, Alter BP, McReynolds LJ
Pediatr Res 2022 Dec;92(6):1671-1680. Epub 2022 Mar 23 doi: 10.1038/s41390-022-02009-8. PMID: 35322185Free PMC Article
Schürch C, Schaefer T, Müller JS, Hanns P, Arnone M, Dumlin A, Schärer J, Sinning I, Wild K, Skokowa J, Welte K, Carapito R, Bahram S, Konantz M, Lengerke C
Blood 2021 Mar 11;137(10):1340-1352. doi: 10.1182/blood.2020008115. PMID: 33227812Free PMC Article
Bogusz-Wójcik A, Kołodziejczyk H, Klaudel-Dreszler M, Oracz G, Pawłowska J, Szalecki M
Ital J Pediatr 2020 Oct 12;46(1):151. doi: 10.1186/s13052-020-00919-z. PMID: 33046118Free PMC Article
Toiviainen-Salo S, Mäyränpää MK, Durie PR, Richards N, Grynpas M, Ellis L, Ikegawa S, Cole WG, Rommens J, Marttinen E, Savilahti E, Mäkitie O
Bone 2007 Dec;41(6):965-72. Epub 2007 Sep 5 doi: 10.1016/j.bone.2007.08.035. PMID: 17920346
Cipolli M
Pancreatology 2001;1(5):543-8. doi: 10.1159/000055858. PMID: 12120235

Recent systematic reviews

Han X, Lu S, Gu C, Bian Z, Xie X, Qiao X
BMC Pediatr 2023 Oct 6;23(1):503. doi: 10.1186/s12887-023-04324-3. PMID: 37803383Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...