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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
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
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]
Authors:
Kasiani Myers   view full author information

Additional descriptions

From OMIM
Shwachman-Diamond syndrome is a multisystem autosomal recessive disorder characterized by exocrine pancreatic dysfunction, bony metaphyseal dysostosis, and varying degrees of marrow dysfunction with cytopenias. Myelodysplastic syndrome and acute myeloid leukemia occur in up to one third of patients (summary by Dror and Freedman, 1999). 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 blood cell fragments 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 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.  https://ghr.nlm.nih.gov/condition/shwachman-diamond-syndrome

Clinical features

Slipped femoral capital epiphyses
MedGen UID:
57704
Concept ID:
C0149887
Disease or Syndrome
A developmental deformity in which the metaphysis of the FEMUR moves proximally and anteriorly away from FEMUR HEAD (epiphysis) at the upper GROWTH PLATE. It is most common in male adolescents and is associated with a greater risk of early OSTEOARTHRITIS of the hip.
Proximal femoral metaphyseal irregularity
MedGen UID:
324485
Concept ID:
C1836320
Finding
Irregularity of the normally smooth surface of the proximal metaphysis of the femur.
Small for gestational age
MedGen UID:
7064
Concept ID:
C0021288
Patient or Disabled Group
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Finding
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Height greater than two standard deviations below the mean of the appropriate reference population for the age and sex of the individual.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Sign or Symptom
Enlargement of the liver.
Exocrine pancreatic insufficiency
MedGen UID:
45295
Concept ID:
C0030293
Disease or Syndrome
Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes.
Neonatal respiratory distress
MedGen UID:
163106
Concept ID:
C0852283
Disease or Syndrome
Respiratory difficulty as newborn.
Acute myeloid leukemia
MedGen UID:
9730
Concept ID:
C0023467
Neoplastic Process
CEBPA-associated familial acute myeloid leukemia (AML) is defined as AML in which a heterozygous germline CEBPA pathogenic variant is present in a family in which multiple individuals have AML. In contrast, sporadic CEBPA-associated AML is defined as AML in which a CEBPA pathogenic variant(s) is identified in leukemic cells but not in the non-leukemic cells. Too few individuals with CEBPA-associated familial AML have been reported to be certain about the natural history of the disease. In the majority of individuals, the age of onset of familial AML appears to be earlier than sporadic AML; disease onset has been reported in persons as young as age 1.8 years and older than age 45 years. The prognosis of CEBPA-associated familial AML appears to be favorable compared with sporadic CEBPA-associated AML. Individuals with CEBPA-associated familial AML who have been cured of their initial disease may be at greater risk of developing additional independent leukemic episodes in addition to the risk of relapse due to preexisting clones.
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.
Slipped femoral capital epiphyses
MedGen UID:
57704
Concept ID:
C0149887
Disease or Syndrome
A developmental deformity in which the metaphysis of the FEMUR moves proximally and anteriorly away from FEMUR HEAD (epiphysis) at the upper GROWTH PLATE. It is most common in male adolescents and is associated with a greater risk of early OSTEOARTHRITIS of the hip.
Metaphyseal dysostosis
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.
Proximal femoral metaphyseal irregularity
MedGen UID:
324485
Concept ID:
C1836320
Finding
Irregularity of the normally smooth surface of the proximal metaphysis of the femur.
Narrow sacroiliac notch
MedGen UID:
337966
Concept ID:
C1850087
Finding
The sacroiliac joint in the bony pelvis connects the sacrum and the ilium of the pelvis, which are joined by strong ligaments. The notch is located directly superior to the joint. This term refers to a reduction in the lateral dimension of the notch.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVShwachman syndrome
Follow this link to review classifications for Shwachman syndrome in Orphanet.

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. 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
Ventura A, Dragovich D, Luxardo P, Zanazzo G
Haematologica 1995 May-Jun;80(3):227-9. PMID: 7545636
Kent A, Murphy GH, Milla P
Arch Dis Child 1990 Dec;65(12):1349-52. PMID: 1702966Free PMC Article

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
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
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
Dhar S, Anderton JM
J Bone Joint Surg Am 1994 Feb;76(2):278-82. PMID: 8113266
Bom EP, van der Sande FM, Tjon RT, Tham A, Hillen HF
J Comput Assist Tomogr 1993 May-Jun;17(3):474-6. PMID: 8491914

Therapy

Hisha H, Kohdera U, Hirayama M, Yamada H, Iguchi-Uehira T, Fan TX, Cui YZ, Yang GX, Li Y, Sugiura K, Inaba M, Kobayashi Y, Ikehara S
Stem Cells 2002;20(4):311-9. doi: 10.1634/stemcells.20-4-311. PMID: 12110700
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
Adachi N, Migita M, Ohta T, Higashi A, Matsuda I
Eur J Pediatr 1997 Jun;156(6):444-8. PMID: 9208238
Ventura A, Dragovich D, Luxardo P, Zanazzo G
Haematologica 1995 May-Jun;80(3):227-9. PMID: 7545636
Woods WG, Krivit W, Lubin BH, Ramsay NK
Am J Pediatr Hematol Oncol 1981 Winter;3(4):347-51. PMID: 7332065

Prognosis

Topa A, Tulinius M, Oldfors A, Hedberg-Oldfors C
Am J Med Genet A 2016 May;170A(5):1155-64. Epub 2016 Feb 11 doi: 10.1002/ajmg.a.37593. PMID: 26866830
Saito-Benz M, Miller HE, Berry MJ
J Paediatr Child Health 2015 Dec;51(12):1228-31. Epub 2015 Jun 17 doi: 10.1111/jpc.12941. PMID: 26081292
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
Mack DR, Forstner GG, Wilschanski M, Freedman MH, Durie PR
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

Topa A, Tulinius M, Oldfors A, Hedberg-Oldfors C
Am J Med Genet A 2016 May;170A(5):1155-64. Epub 2016 Feb 11 doi: 10.1002/ajmg.a.37593. PMID: 26866830
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. PMID: 21659346

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