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Specific granule deficiency 2(SGD2)

MedGen UID:
1371952
Concept ID:
C4479548
Disease or Syndrome
Synonym: SGD2
 
Gene (location): SMARCD2 (17q23.3)
 
Monarch Initiative: MONDO:0044208
OMIM®: 617475

Definition

Specific granule deficiency-2 (SGD2) is an autosomal recessive immunologic disorder characterized by recurrent infections due to defective neutrophil development. Bone marrow findings include paucity of neutrophil granulocytes, absence of granule proteins in neutrophils, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. The disorder is apparent from infancy, and patients may die in early childhood unless they undergo hematopoietic stem cell transplantation. Most patients have additional findings, including delayed development, mild dysmorphic features, tooth abnormalities, and distal skeletal defects (Witzel et al., 2017). For a discussion of genetic heterogeneity of SGD, see SGD1 (245480). [from OMIM]

Clinical features

From HPO
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.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Sandal gap
MedGen UID:
374376
Concept ID:
C1840069
Finding
A widely spaced gap between the first toe (the great toe) and the second toe.
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.
Intractable diarrhea
MedGen UID:
148164
Concept ID:
C0743178
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.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Simple ear
MedGen UID:
140913
Concept ID:
C0431483
Congenital Abnormality
The pinna has fewer folds and grooves than usual.
Abnormal pinna morphology
MedGen UID:
167800
Concept ID:
C0857379
Congenital Abnormality
An abnormality of the pinna, which is also referred to as the auricle or external 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.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Bone marrow maturation arrest
MedGen UID:
549798
Concept ID:
C0302173
Cell or Molecular Dysfunction
Interruption of the procecss of diffferentiation of hematopoietic cells in the bone marrow, manifested by an increased proportion of immature cells in the bone marrow.
Amelogenesis imperfecta
MedGen UID:
240
Concept ID:
C0002452
Congenital Abnormality
A developmental dysplasia of the dental enamel.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
Absent neutrophil specific granules
MedGen UID:
868458
Concept ID:
C4022852
Finding
Lack of specific granules in neutrophils.
Conical tooth
MedGen UID:
82730
Concept ID:
C0266037
Congenital Abnormality
An abnormal conical form of the teeth, that is, a tooth whose sides converge or taper together incisally.
Tooth malposition
MedGen UID:
377692
Concept ID:
C1852504
Finding
Abnormal alignment, positioning, or spacing of the teeth, i.e., misaligned teeth.
Acanthosis nigricans
MedGen UID:
54
Concept ID:
C0000889
Disease or Syndrome
A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Hyperextensible skin
MedGen UID:
66023
Concept ID:
C0241074
Finding
A condition in which the skin can be stretched beyond normal, and then returns to its initial position.
Nail dysplasia
MedGen UID:
331737
Concept ID:
C1834405
Congenital Abnormality
The presence of developmental dysplasia of the nail.
Fragile nails
MedGen UID:
341661
Concept ID:
C1856963
Finding
Nails that easily break.
Neonatal omphalitis
MedGen UID:
510678
Concept ID:
C0158947
Disease or Syndrome
An infection of the umbilicus and/or surrounding tissues occurring in the neonatal period.
Delayed umbilical cord separation
MedGen UID:
226769
Concept ID:
C1260438
Pathologic Function
Separation of the umbilical cord occurs at an abnormally late timepoint.

Professional guidelines

PubMed

Uzel G, Holland SM
Curr Allergy Asthma Rep 2002 Sep;2(5):385-91. doi: 10.1007/s11882-002-0071-5. PMID: 12165204

Recent clinical studies

Etiology

Ye Y, Carlsson G, Karlsson-Sjöberg JM, Borregaard N, Modéer TU, Andersson ML, Pütsep KL
Sci Rep 2015 Jun 29;5:11685. doi: 10.1038/srep11685. PMID: 26119962Free PMC Article
Lomax KJ, Malech HL, Gallin JI
Blood Rev 1989 Jun;3(2):94-104. doi: 10.1016/0268-960x(89)90004-0. PMID: 2673450

Diagnosis

Banday AZ, Kaur A, Akagi T, Bhattarai D, Muraoka M, Dev D, Das J, Sachdeva MUS, Karmakar I, Arora K, Kaur G, Pandiarajan V, Jindal AK, Wada T, Koeffler HP, Suri D, Ahluwalia J, Kanegane H, Bhatia P, Rawat A, Singh S
J Clin Immunol 2022 Oct;42(7):1434-1450. Epub 2022 Jun 20 doi: 10.1007/s10875-022-01304-7. PMID: 35726044
Kihtir Z, Çelik K, Tayfun Küpesiz F, Küpesiz OA, Kocacik Uygun DF, Arayici S, Ongun H, Acarbulut İ, Sağlam C, Ceylaner G, Bingöl A
Pediatr Allergy Immunol Pulmonol 2022 Mar;35(1):43-46. doi: 10.1089/ped.2021.0070. PMID: 35320004
Schim van der Loeff I, Sprenkeler EGG, Tool ATJ, Abinun M, Grainger A, Engelhardt KR, van Houdt M, Janssen H, Kuijpers TW, Hambleton S
J Allergy Clin Immunol 2021 Jun;147(6):2381-2385.e2. Epub 2020 Dec 3 doi: 10.1016/j.jaci.2020.11.025. PMID: 33279574Free PMC Article
Wada T, Akagi T
Crit Rev Immunol 2016;36(4):349-358. doi: 10.1615/CritRevImmunol.2017019385. PMID: 28322138
Ye Y, Carlsson G, Karlsson-Sjöberg JM, Borregaard N, Modéer TU, Andersson ML, Pütsep KL
Sci Rep 2015 Jun 29;5:11685. doi: 10.1038/srep11685. PMID: 26119962Free PMC Article

Therapy

Taverniti V, Koirala R, Dalla Via A, Gargari G, Leonardis E, Arioli S, Guglielmetti S
Nutrients 2019 Jan 29;11(2) doi: 10.3390/nu11020285. PMID: 30699901Free PMC Article

Prognosis

Taverniti V, Koirala R, Dalla Via A, Gargari G, Leonardis E, Arioli S, Guglielmetti S
Nutrients 2019 Jan 29;11(2) doi: 10.3390/nu11020285. PMID: 30699901Free PMC Article
Shigemura T, Yamazaki T, Shiohara M, Kobayashi N, Naganuma K, Koike K, Agematsu K
J Clin Immunol 2014 Oct;34(7):780-3. Epub 2014 Aug 1 doi: 10.1007/s10875-014-0082-8. PMID: 25081842

Clinical prediction guides

Banday AZ, Kaur A, Akagi T, Bhattarai D, Muraoka M, Dev D, Das J, Sachdeva MUS, Karmakar I, Arora K, Kaur G, Pandiarajan V, Jindal AK, Wada T, Koeffler HP, Suri D, Ahluwalia J, Kanegane H, Bhatia P, Rawat A, Singh S
J Clin Immunol 2022 Oct;42(7):1434-1450. Epub 2022 Jun 20 doi: 10.1007/s10875-022-01304-7. PMID: 35726044
Serwas NK, Huemer J, Dieckmann R, Mejstrikova E, Garncarz W, Litzman J, Hoeger B, Zapletal O, Janda A, Bennett KL, Kain R, Kerjaschky D, Boztug K
Front Immunol 2018;9:588. Epub 2018 Mar 29 doi: 10.3389/fimmu.2018.00588. PMID: 29651288Free PMC Article
Wada T, Akagi T
Crit Rev Immunol 2016;36(4):349-358. doi: 10.1615/CritRevImmunol.2017019385. PMID: 28322138
Pass MB, Borregaard N, Cowland JB
Leuk Res 2007 Jun;31(6):827-37. Epub 2006 Aug 30 doi: 10.1016/j.leukres.2006.07.019. PMID: 16942795
Shiohara M, Gombart AF, Sekiguchi Y, Hidaka E, Ito S, Yamazaki T, Koeffler HP, Komiyama A
J Leukoc Biol 2004 Feb;75(2):190-7. Epub 2003 Oct 23 doi: 10.1189/jlb.0203063. PMID: 14576362

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