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Shwachman-Diamond syndrome 2(SDS2)

MedGen UID:
1634617
Concept ID:
C4693704
Disease or Syndrome
Synonyms: SDS2; SHWACHMAN-DIAMOND SYNDROME 2
 
Gene (location): EFL1 (15q25.2)
 
Monarch Initiative: MONDO:0044205
OMIM®: 617941

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 multilineage cytopenias and susceptibility to myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML); and bone abnormalities. In almost all affected children, persistent or intermittent neutropenia is an early finding. Short stature and recurrent infections are common. [from GeneReviews]
Authors:
Adam Nelson  |  Kasiani Myers   view full author information

Additional description

From OMIM
Shwachman-Diamond syndrome-2 (SDS2) is characterized by exocrine pancreatic dysfunction, hematopoietic abnormalities, short stature, and metaphyseal dysplasia (Stepensky et al., 2017). For a discussion of genetic heterogeneity of Shwachman-Diamond syndrome, see SDS1 (260400).  http://www.omim.org/entry/617941

Clinical features

From HPO
Genu varum
MedGen UID:
154257
Concept ID:
C0544755
Finding
A positional abnormality marked by outward bowing of the legs in which the knees stay wide apart when a person stands with the feet and ankles together.
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.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
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.
Hyperechogenic pancreas
MedGen UID:
347581
Concept ID:
C1857945
Disease or Syndrome
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
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.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Normocytic anemia
MedGen UID:
39310
Concept ID:
C0085577
Disease or Syndrome
A kind of anemia in which the volume of the red blood cells is normal.
Prolonged partial thromboplastin time
MedGen UID:
66815
Concept ID:
C0240671
Finding
Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms.
Prolonged prothrombin time
MedGen UID:
208879
Concept ID:
C0853225
Finding
Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
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.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Subglottic stenosis
MedGen UID:
68668
Concept ID:
C0238441
Anatomical Abnormality
Congenital laryngomalacia
MedGen UID:
120500
Concept ID:
C0264303
Anatomical Abnormality
Laryngomalacia is a congenital abnormality of the laryngeal cartilage in which the cartilage is floppy and prolapses over the larynx during inspiration.
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.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.

Professional guidelines

PubMed

Davies SM
Hematology Am Soc Hematol Educ Program 2019 Dec 6;2019(1):105-109. doi: 10.1182/hematology.2019000020. PMID: 31808891Free 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
Burroughs L, Woolfrey A, Shimamura A
Hematol Oncol Clin North Am 2009 Apr;23(2):233-48. doi: 10.1016/j.hoc.2009.01.007. PMID: 19327581Free PMC Article

Recent clinical studies

Etiology

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
Rafei H, DiNardo CD
Best Pract Res Clin Haematol 2019 Jun;32(2):163-176. Epub 2019 May 3 doi: 10.1016/j.beha.2019.05.001. PMID: 31203998Free PMC Article
Bezzerri V, Cipolli M
Mol Diagn Ther 2019 Apr;23(2):281-290. doi: 10.1007/s40291-018-0368-2. PMID: 30413969
Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, Grauman PV, Hu ZH, Spellman SR, Lee SJ, Verneris MR, Hsu K, Fleischhauer K, Cutler C, Antin JH, Neuberg D, Ebert BL
N Engl J Med 2017 Feb 9;376(6):536-547. doi: 10.1056/NEJMoa1611604. PMID: 28177873Free PMC Article
Dall'oca C, Bondi M, Merlini M, Cipolli M, Lavini F, Bartolozzi P
Musculoskelet Surg 2012 Aug;96(2):81-8. Epub 2011 Dec 27 doi: 10.1007/s12306-011-0174-z. PMID: 22201042

Diagnosis

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
Bogusz-Wójcik A, Kołodziejczyk H, Moszczyńska E, Klaudel-Dreszler M, Oracz G, Pawłowska J, Szalecki M
Endokrynol Pol 2021;72(3):211-216. Epub 2021 Feb 23 doi: 10.5603/EP.a2021.0014. PMID: 33619711
Rafei H, DiNardo CD
Best Pract Res Clin Haematol 2019 Jun;32(2):163-176. Epub 2019 May 3 doi: 10.1016/j.beha.2019.05.001. PMID: 31203998Free PMC Article
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

Therapy

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
Shibata S, Inano S, Watanabe M, Fujiwara K, Ueno H, Nannya Y, Kanda J, Kawasaki N, Okamoto Y, Takiuchi Y, Fukunaga A, Tabata S, Ogawa S, Takaori-Kondo A, Kitano T
Int J Hematol 2022 Mar;115(3):428-434. Epub 2021 Oct 26 doi: 10.1007/s12185-021-03251-2. PMID: 34704233
Bogusz-Wójcik A, Kołodziejczyk H, Moszczyńska E, Klaudel-Dreszler M, Oracz G, Pawłowska J, Szalecki M
Pediatr Endocrinol Diabetes Metab 2021;27(2):87-92. doi: 10.5114/pedm.2021.105298. PMID: 33878854Free 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
Dall'oca C, Bondi M, Merlini M, Cipolli M, Lavini F, Bartolozzi P
Musculoskelet Surg 2012 Aug;96(2):81-8. Epub 2011 Dec 27 doi: 10.1007/s12306-011-0174-z. PMID: 22201042

Prognosis

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
Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, Grauman PV, Hu ZH, Spellman SR, Lee SJ, Verneris MR, Hsu K, Fleischhauer K, Cutler C, Antin JH, Neuberg D, Ebert BL
N Engl J Med 2017 Feb 9;376(6):536-547. doi: 10.1056/NEJMoa1611604. PMID: 28177873Free PMC Article
Alter BP, Giri N, Savage SA, Rosenberg PS
Haematologica 2015 Jan;100(1):49-54. Epub 2014 Oct 10 doi: 10.3324/haematol.2014.114389. PMID: 25304614Free PMC Article
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
Smith OP, Hann IM, Chessells JM, Reeves BR, Milla P
Br J Haematol 1996 Aug;94(2):279-84. doi: 10.1046/j.1365-2141.1996.d01-1788.x. PMID: 8759887

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
Bogusz-Wójcik A, Kołodziejczyk H, Moszczyńska E, Klaudel-Dreszler M, Oracz G, Pawłowska J, Szalecki M
Pediatr Endocrinol Diabetes Metab 2021;27(2):87-92. doi: 10.5114/pedm.2021.105298. PMID: 33878854Free 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
Cesaro S, Pillon M, Sauer M, Smiers F, Faraci M, de Heredia CD, Wynn R, Greil J, Locatelli F, Veys P, Uyttebroeck A, Ljungman P, Chevalier P, Ansari M, Badell I, Güngör T, Salim R, Tischer J, Tecchio C, Russell N, Chybicka A, Styczynski J, Krivan G, Smith O, Stein J, Afanasyev B, Pochon C, Menconi MC, Bosman P, Mauro M, Tridello G, de Latour RP, Dufour C
Bone Marrow Transplant 2020 Sep;55(9):1796-1809. Epub 2020 Mar 19 doi: 10.1038/s41409-020-0863-z. PMID: 32203264
Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, Grauman PV, Hu ZH, Spellman SR, Lee SJ, Verneris MR, Hsu K, Fleischhauer K, Cutler C, Antin JH, Neuberg D, Ebert BL
N Engl J Med 2017 Feb 9;376(6):536-547. doi: 10.1056/NEJMoa1611604. PMID: 28177873Free PMC Article

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