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Shwachman syndrome(SDS)

MedGen UID:
124418
Concept ID:
C0272170
Disease or Syndrome
Synonyms: Lipomatosis of pancreas, congenital; Pancreatic insufficiency and bone marrow dysfunction; SDS; Shwachman-Bodian syndrome; Shwachman-Diamond Syndrome
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Shwachman syndrome (89454001); Shwachman-Diamond syndrome (89454001); Metaphyseal chondrodysplasia with pancreatic insufficiency AND neutropenia (89454001); Metaphyseal dysplasia with malabsorption and neutropenia (89454001); Metaphyseal chondrodysplasia, Shwachman type (89454001); Schwachman's syndrome (89454001); Schwachman-Diamond syndrome (89454001); Schwachman-Bodian syndrome (89454001); Shwachman's syndrome (89454001); Congenital lipomatosis of pancreas (89454001); Schwachmann-Diamond syndrome (89454001)
 
Gene (location): SBDS (7q11.21)
OMIM®: 260400
Orphanet: ORPHA811

Disease characteristics

Excerpted from the GeneReview: Shwachman-Diamond Syndrome
Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic dysfunction with malabsorption, malnutrition, and growth failure; hematologic abnormalities with single- or multi-lineage 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]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Kasiani Myers   view full author information

Additional descriptions

From OMIM
Shwachman-Diamond syndrome is characterized primarily by exocrine pancreatic insufficiency, hematologic abnormalities, including increased risk of malignant transformation, and skeletal abnormalities. For a review of Shwachman-Diamond syndrome, see Dror and Freedman (2002).  http://www.omim.org/entry/260400
From GHR
Shwachman-Diamond syndrome is an inherited condition that affects many parts of the body, particularly the bone marrow, pancreas, and skeletal system. 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 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 such as pneumonia, recurrent ear infections (otitis media), and skin infections. 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 that affect blood cell production, 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 the 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 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 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 this condition 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.  http://ghr.nlm.nih.gov/condition/shwachman-diamond-syndrome

Clinical features

Small for gestational age
MedGen UID:
44199
Concept ID:
C0024032
Finding
Refers to a fetus or infant who is smaller than expected for the age or gender, or who has a birth weight less than the 10th percentile.
Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Sign or Symptom
Slower than normal rate of weight increase.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Myelodysplasia
MedGen UID:
368407
Concept ID:
C1963099
Finding
Acute myeloid leukemia
MedGen UID:
505691
Concept ID:
CN004254
Finding
A form of leukemia characterized by overproduction of an early myeloid cell.
Nephrocalcinosis
MedGen UID:
504348
Concept ID:
CN000117
Finding
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Microdontia
MedGen UID:
342456
Concept ID:
C1850267
Finding
Carious teeth
MedGen UID:
401327
Concept ID:
C1867882
Finding
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Sign or Symptom
A finding referring to walking difficulties.
Cognitive impairment
MedGen UID:
383844
Concept ID:
C1856145
Finding
Intellectual disability, mild
MedGen UID:
504770
Concept ID:
CN001151
Finding
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
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:
504802
Concept ID:
CN001216
Finding
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.
Type I diabetes mellitus
MedGen UID:
334999
Concept ID:
C1844664
Finding
Enlargement of the costochondral junction
MedGen UID:
116079
Concept ID:
C0239129
Finding
Coxa vara
MedGen UID:
116081
Concept ID:
C0239138
Finding
Hip deformity in which the femoral neck leans forward resulting in a decrease in the angle between femoral neck and its shaft. It may be congenital often syndromic, acquired, or developmental.
Short thorax
MedGen UID:
140876
Concept ID:
C0426789
Finding
Proximal femoral metaphyseal irregularity
MedGen UID:
324485
Concept ID:
C1836320
Finding
Ovoid vertebral bodies
MedGen UID:
373195
Concept ID:
C1836864
Finding
Anterior rib cupping
MedGen UID:
337520
Concept ID:
C1846154
Finding
Irregular ossification at anterior rib ends
MedGen UID:
376700
Concept ID:
C1850083
Finding
Narrow sacroiliac notch
MedGen UID:
337966
Concept ID:
C1850087
Finding
Metaphyseal widening
MedGen UID:
344455
Concept ID:
C1855248
Finding
A radiologic finding characterized by an increased width of the metaphyseal regions. It is seen in rickets.
Reduced bone mineral density
MedGen UID:
393152
Concept ID:
C2674432
Finding
Metaphyseal sclerosis
MedGen UID:
765440
Concept ID:
C3552526
Finding
Pectus carinatum
MedGen UID:
504592
Concept ID:
CN000722
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Narrow chest
MedGen UID:
504594
Concept ID:
CN000728
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.
Scoliosis
MedGen UID:
427922
Concept ID:
CN002409
Finding
The presence of an abnormal lateral curvature of the spine.
Delayed skeletal maturation
MedGen UID:
505344
Concept ID:
CN002495
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.
Metaphyseal chondrodysplasia
MedGen UID:
505859
Concept ID:
CN005173
Finding
An abnormality of skeletal development characterized by a disturbance of the metaphysis and its histological structure with relatively normal epiphyses and vertebrae.
Proximal femoral epiphysiolysis
MedGen UID:
505914
Concept ID:
CN005626
Finding
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.
Steatorrhea
MedGen UID:
20948
Concept ID:
C0038238
Disease or Syndrome
A condition that is characterized by chronic fatty DIARRHEA, a result of abnormal DIGESTION and/or INTESTINAL ABSORPTION of FATS.
Exocrine pancreatic insufficiency
MedGen UID:
504939
Concept ID:
CN001582
Finding
Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes.
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Elevated hepatic transaminases
MedGen UID:
505403
Concept ID:
CN002632
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.
Eczema
MedGen UID:
504663
Concept ID:
CN000902
Finding
Eczema is a form of dermatitis. The term eczema is broadly applied to a range of persistent skin conditions and can be related to a number of underlying conditions. Manifestations of eczema can include dryness and recurring skin rashes with redness, skin edema, itching and dryness, crusting, flaking, blistering, cracking, oozing, or bleeding.
Ichthyosis
MedGen UID:
429191
Concept ID:
CN007091
Finding
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Myocardial necrosis
MedGen UID:
504919
Concept ID:
CN001546
Finding
Neutropenia
MedGen UID:
18030
Concept ID:
C0027947
Disease or Syndrome
An abnormal decrease in the number of neutrophils, a type of white blood cell.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A finding based on laboratory test results that indicate a decrease in number of platelets in a blood specimen.
Persistence of hemoglobin F
MedGen UID:
68693
Concept ID:
C0239941
Finding
Myelodysplasia
MedGen UID:
368407
Concept ID:
C1963099
Finding
Pancytopenia
MedGen UID:
504982
Concept ID:
CN001696
Finding
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Macrocytic anemia
MedGen UID:
505031
Concept ID:
CN001784
Finding
A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
Acute myeloid leukemia
MedGen UID:
505691
Concept ID:
CN004254
Finding
A form of leukemia characterized by overproduction of an early myeloid cell.
Bone marrow hypocellularity
MedGen UID:
505824
Concept ID:
CN004897
Finding
A reduced number of hematopoietic cells present in the bone marrow.
Type I diabetes mellitus
MedGen UID:
334999
Concept ID:
C1844664
Finding
Neonatal respiratory distress
MedGen UID:
505314
Concept ID:
CN002404
Finding
Respiratory difficulty as newborn.
Neutropenia
MedGen UID:
18030
Concept ID:
C0027947
Disease or Syndrome
An abnormal decrease in the number of neutrophils, a type of white blood cell.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Acute myeloid leukemia
MedGen UID:
505691
Concept ID:
CN004254
Finding
A form of leukemia characterized by overproduction of an early myeloid cell.
Coxa vara
MedGen UID:
116081
Concept ID:
C0239138
Finding
Hip deformity in which the femoral neck leans forward resulting in a decrease in the angle between femoral neck and its shaft. It may be congenital often syndromic, acquired, or developmental.
Proximal femoral metaphyseal irregularity
MedGen UID:
324485
Concept ID:
C1836320
Finding
Metaphyseal widening
MedGen UID:
344455
Concept ID:
C1855248
Finding
A radiologic finding characterized by an increased width of the metaphyseal regions. It is seen in rickets.
Metaphyseal sclerosis
MedGen UID:
765440
Concept ID:
C3552526
Finding
Metaphyseal chondrodysplasia
MedGen UID:
505859
Concept ID:
CN005173
Finding
An abnormality of skeletal development characterized by a disturbance of the metaphysis and its histological structure with relatively normal epiphyses and vertebrae.
Proximal femoral epiphysiolysis
MedGen UID:
505914
Concept ID:
CN005626
Finding
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGShwachman syndrome

Professional guidelines

PubMed

Dror Y, Donadieu J, Koglmeier J, Dodge J, Toiviainen-Salo S, Makitie O, Kerr E, Zeidler C, Shimamura A, Shah N, Cipolli M, Kuijpers T, Durie P, Rommens J, Siderius L, Liu JM
Ann N Y Acad Sci 2011 Dec;1242:40-55. doi: 10.1111/j.1749-6632.2011.06349.x. PMID: 22191555

Recent clinical studies

Etiology

Minelli A, Maserati E, Nicolis E, Zecca M, Sainati L, Longoni D, Lo Curto F, Menna G, Poli F, De Paoli E, Cipolli M, Locatelli F, Pasquali F, Danesino C
Leukemia 2009 Apr;23(4):708-11. Epub 2009 Jan 15 doi: 10.1038/leu.2008.369. [Epub ahead of print] PMID: 19148133
Porta G, Mattarucchi E, Maserati E, Pressato B, Valli R, Morerio C, Zecca M, Panarello C, Locatelli F, Lo Curto F, Pasquali F
J Pediatr Hematol Oncol 2007 Mar;29(3):163-5. doi: 10.1097/MPH.0b013e31803b958e. PMID: 17356395
Ginzberg H, Shin J, Ellis L, Morrison J, Ip W, Dror Y, Freedman M, Heitlinger LA, Belt MA, Corey M, Rommens JM, Durie PR
J Pediatr 1999 Jul;135(1):81-8. PMID: 10393609
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Diagnosis

Porta G, Mattarucchi E, Maserati E, Pressato B, Valli R, Morerio C, Zecca M, Panarello C, Locatelli F, Lo Curto F, Pasquali F
J Pediatr Hematol Oncol 2007 Mar;29(3):163-5. doi: 10.1097/MPH.0b013e31803b958e. PMID: 17356395
Ginzberg H, Shin J, Ellis L, Morrison J, Ip W, Dror Y, Freedman M, Heitlinger LA, Belt MA, Corey M, Rommens JM, Durie PR
J Pediatr 1999 Jul;135(1):81-8. PMID: 10393609
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Gastroenterology 1982 Jul;83(1 Pt 1):22-7. PMID: 7075943

Therapy

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Stem Cells 2002;20(4):311-9. doi: 10.1634/stemcells.20-4-311. PMID: 12110700
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Ristola M, Savilahti E, Leirisalo-Repo M, Repo H
Eur J Pediatr 1991 Jan;150(3):173-8. PMID: 2044587
Woods WG, Krivit W, Lubin BH, Ramsay NK
Am J Pediatr Hematol Oncol 1981 Winter;3(4):347-51. PMID: 7332065

Prognosis

Pressato B, Valli R, Marletta C, Mare L, Montalbano G, Curto FL, Pasquali F, Maserati E
J Pediatr Hematol Oncol 2015 May;37(4):307-10. doi: 10.1097/MPH.0000000000000268. PMID: 25887640
Nakaya T, Kurata A, Hashimoto H, Nishimata S, Kashiwagi Y, Fujita K, Kawashima H, Kuroda M
Pathol Int 2014 Feb;64(2):75-80. doi: 10.1111/pin.12133. PMID: 24629175
Filippi L, Tronchin M, Pezzati M, Chiti G, Dani C, Vichi GF, Rubaltelli FF
J Pediatr Gastroenterol Nutr 2002 Feb;34(2):219-23. PMID: 11840044
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Gastroenterology 1996 Dec;111(6):1593-602. PMID: 8942739
Goeteyn M, Oranje AP, Vuzevski VD, de Groot R, van Suijlekom-Smit LW
Arch Dermatol 1991 Feb;127(2):225-30. PMID: 1990988

Clinical prediction guides

Pressato B, Valli R, Marletta C, Mare L, Montalbano G, Curto FL, Pasquali F, Maserati E
J Pediatr Hematol Oncol 2015 May;37(4):307-10. doi: 10.1097/MPH.0000000000000268. PMID: 25887640
Maserati E, Minelli A, Olivieri C, Bonvini L, Marchi A, Bozzola M, Danesino C, Scappaticci S, Pasquali F
Cancer Genet Cytogenet 2000 Sep;121(2):167-71. PMID: 11063802
Ginzberg H, Shin J, Ellis L, Morrison J, Ip W, Dror Y, Freedman M, Heitlinger LA, Belt MA, Corey M, Rommens JM, Durie PR
J Pediatr 1999 Jul;135(1):81-8. PMID: 10393609
Kent A, Murphy GH, Milla P
Arch Dis Child 1990 Dec;65(12):1349-52. PMID: 1702966Free PMC Article
Woods WG, Krivit W, Lubin BH, Ramsay NK
Am J Pediatr Hematol Oncol 1981 Winter;3(4):347-51. PMID: 7332065

Recent systematic reviews

Parikh S, Bessler M
Curr Opin Pediatr 2012 Feb;24(1):23-32. doi: 10.1097/MOP.0b013e32834eca77. PMID: 22227778Free PMC Article
Dror Y, Donadieu J, Koglmeier J, Dodge J, Toiviainen-Salo S, Makitie O, Kerr E, Zeidler C, Shimamura A, Shah N, Cipolli M, Kuijpers T, Durie P, Rommens J, Siderius L, Liu JM
Ann N Y Acad Sci 2011 Dec;1242:40-55. doi: 10.1111/j.1749-6632.2011.06349.x. PMID: 22191555
Tsangaris E, Klaassen R, Fernandez CV, Yanofsky R, Shereck E, Champagne J, Silva M, Lipton JH, Brossard J, Michon B, Abish S, Steele M, Ali K, Dower N, Athale U, Jardine L, Hand JP, Odame I, Canning P, Allen C, Carcao M, Beyene J, Roifman CM, Dror Y
J Med Genet 2011 Sep;48(9):618-28. Epub 2011 Jun 9 doi: 10.1136/jmg.2011.089821. [Epub ahead of print] PMID: 21659346

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