Table 1.
Syndrome-associated neutropenia.
| Disease | Gene chromosome inheritance | Clinical features | G-CSF responsive | Risk of progression to MDS/AML | Evidence of successful HSCT | References |
|---|---|---|---|---|---|---|
| Schwachman Diamond Syndrome (SDS) |
SBDS 7q11.21 AR |
Bone marrow failure Exocrine pancreas dysfunction Malabsorption Skeletal abnormalities Neurocognitive deficit Recurrent infections (9) |
Yes | Yes 15–30% progress to MDS |
Yes (see text) | (10–14) |
| G6PC3 deficiency |
G6PC3 17q21 AR |
SCN Intermittent thrombocytopenia Congential heart disease Urogenital anomalies Dysmorphism Growth and developmental delay Gastrointestinal disease (Crohn's Disease, chronic diarrhea with steatorrhea) |
Yes | Yes | Yes | (15–17) |
| Glycogen storage disease type 1b |
G6PT1 11q23 AR |
Neutropenia Hypoglycemia Recurrent infections Inflammatory bowel disease Liver diseases and hepatosplenomegaly Hypertriglyceridemia |
Yes | Yes | Yes | (18, 19) |
| Cohen syndrome |
VPS13B (also called COH1) 8q22.2 AR |
Decreased fetal activity and low birth weight Neutropenia/SCN Obesity (truncal with normal BMI) Hypotonia Dysmorphisms, dental anomalies, poor vision, and limb abnormalities Intellectual disability (severe in 22% of cases) |
Yes | None reported | No | (20) |
| Barth syndrome |
TAZ Xq28 X-linked |
Neutropenia (fluctuating) with occasional monocytosis Dilated cardiomyopathy and rhythm abnormalities Skeletal myopathy Growth delay Developmental delay Hypoglycemia Early death |
Yes | None reported | No | (21–23) |
| Clericuzio syndrome (Poikiloderma with neutropenia) |
USB1 16q21 AR |
Inflammatory eczematous rash (6–12 months) Post-inflammatory Poikiloderma (>2 years) Neutropenia Recurrent sinopulmonary infections and bronchiectasis Nail dystrophy, palmar/plantar hyperkeratosis Reactive airway disease Hypogonadotropic hypogonadism Mid-facial retrusion Calcinosis cutis Non-healing skin ulcers |
Yes | Yes | No | (24, 25) |
| VPS45 deficiency (See text) | VPS45 1q21-22 AR |
BMF Neutropenia non-responsive to G-CSF Recurrent, severe bacterial, and fungal infections Extramedullary hematopoiesis with hepatosplenomegaly Nephromegaly |
No | Unknown | Yes (see text) | (26–30) |
| P14/LAMTOR2 |
LAMTOR2/MAPBPIP 3′ UTR p14 AR |
SCN Partial albinism B-cell deficiency CD8 deficiency Coarse facial features |
Yes | None reported | No | (31) |
| JAGN1 | JAGN1 3p25.3 AR |
SCN with increased apoptosis of neutrophils (variable) Recurrent infections Bone, dental, pancreatic insufficiency Failure to thrive Developmental delay |
Variable | Yes | Yes (conditioning regimen not specified in literature) | (32, 33) |
| 3-methylglutaconic acid | CLBP 11q13.4 AR |
SCN Recurrent infections Progressive brain atrophy with intellectual disability Movement disorder Cataracts Movement disorder |
Yes | Yes | No | (34) |
| SMARCD2 | SMARCD2 17q23.3 AR |
Neutropenia Delayed separation of the umbilical cord Recurrent infection Chronic diarrhea Developmental delay Dysmorphic features |
No | Yes | No | (35) |
| WDR1 |
WDR1 AR 4p16.1 |
Neutropenia with impaired lymphoid function Mild learning disability Aphthous stomatitis and skin ulcers Pneumonia Gout Pancreatitis Glioblastoma Dysmorphic features in some patients |
Unclear | Yes | No | (36–38) |
| HYOU |
HYOU1 AR 11q23.3 |
Neutropenia Recurrent oral herpes infection Hypoglycemia Autoimmunity |
Yes | None reported | No | (39) |