Shwachman–Diamond syndrome presenting in a premature infant as pancytopenia

Black, L. Vandy; Soltau, Thomas D.; Kelly, David R.; Berkow, Roger L.

doi:10.1002/pbc.21550

Cited by 8 publications

(9 citation statements)

References 11 publications

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“…[17][18][19][20][21][22][23] The terminology non-malignant SC was preferred to aplastic anemia, because routine bone marrow samples from SDS patients exhibited dysgranulopoietic features or abnormalities of granulopoietic maturation. As in Fanconi anemia, the dyserythropoiesis, hyposegmentation or condensed chromatin should not be considered as a sign of myelodysplasia, 37 unless it is observed in more than 50% of the neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

et al. 2012

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The online version of this article has a Supplementary Appendix. BackgroundPatients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. Design and MethodsOne hundred and two patients with Shwachman-Diamond syndrome, with a median followup of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20×10 9 /L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. ResultsSevere cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by nonmalignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. ConclusionsPatients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.Key words: Shwachman-Diamond syndrome, genotype, aplastic anemia, secondary leukemia, cytopenia, myelodysplasia, monosomy 7.Citation: Donadieu J, Fenneteau O, Beaupain B, Beaufils S, Bellanger F, Mahlaoui N, Lambilliotte A, Aladjidi N, Bertrand Y, Mialou V, Perot C, Michel G, Fouyssac F, Paillard C, Gandemer V, Boutard P, Schmitz J, Morali A, Leblanc T, Bellanné-Chantelot C, and Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

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Section: Discussionmentioning

confidence: 99%

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

et al. 2012

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“…Neonatal forms have been described, with respiratory distress, narrow thorax, pancytopenia [61,62], and especially neurological involvement (mental retardation) [63], predominant gastrointestinal disorders (gluten intolerance), growth retardation in the second year of life, and predominant bone involvement suggestive of a constitutional bone disorder [64]. Depending on the presenting manifestations, differential diagnoses include Cystic fibrosis, Pearson's syndrome (characterized by cytologic abnormalities and especially mitochondrial respiratory chain defects), Fanconi anemia (distinguished by the constitutional karyotype) and gluten intolerance.…”

Section: Congenital Neutropenia - Classification and Etiologymentioning

confidence: 99%

Congenital neutropenia: diagnosis, molecular bases and patient management

Donadieu

Fenneteau

Beaupain

et al. 2011

Orphanet J Rare Dis

183

191

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The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l.When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease.Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant.About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia.Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified.Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF). G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia.

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“…The lack of a specific SDS phenotype associated with pregnancy complications in our cohort may be explained by the small sample size of mothers with offspring with SDS. Published case reports of newborns with SDS suggest prenatal complications due to poor fetal growth, malformations, and cytopenia, leading to fetal distress and preterm delivery of severely affected neonates …”

Section: Discussionmentioning

confidence: 99%

Pregnancy outcomes in mothers of offspring with inherited bone marrow failure syndromes

Giri

Reed

Stratton

et al. 2017

Pediatric Blood & Cancer

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Background: Children with inherited bone marrow failure syndromes (IBMFSs) may be symptomatic in utero, resulting in maternal and fetal problems during the pregnancy. Subsequent pregnancies by their mothers should be considered "high risk". Methods:We retrospectively analyzed outcomes of 575 pregnancies in 165 unaffected mothers of offspring with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS) for events noted during pregnancy, labor, and delivery. We compared outcomes of pregnancies with affected and unaffected offspring within each group of mothers and with the general population. Results:The rates of miscarriage (12-20%), elective abortion (5-10%), and live birth (68-78%) among mothers of all IBMFS groups were similar and comparable with general population rates but recurrent miscarriages (≥2) were significantly more common in mothers of offspring with DBA and SDS. Offspring with FA were more frequently born small for gestational age (SGA) than unaffected babies (39% vs. 4%) and had fetal malformations (46%) with 18% having three or more, often necessitating early delivery and surgery; offspring with DC had higher rates of SGA (39% vs. 8%) and fetal distress (26% vs. 3%); and offspring with DBA had fetal hypoxia (19% vs. 1%) leading to preterm and emergency cesarean deliveries (26% vs. 6%). Offspring with early-onset severe phenotypes had the most prenatal and peripartum adverse events. Conclusion:We identified the high-risk nature of pregnancies in mothers with IBMFS-affected fetuses, suggesting the need for prepregnancy counseling and monitoring of subsequent pregnancies by high-risk fetal-maternal specialists.

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Shwachman–Diamond syndrome presenting in a premature infant as pancytopenia

Cited by 8 publications

References 11 publications

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

Congenital neutropenia: diagnosis, molecular bases and patient management

Pregnancy outcomes in mothers of offspring with inherited bone marrow failure syndromes

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