CSF1R-ALSP/BANDDOS

Knowing the best moment to treat CSF1R-ALSP, ideally before major damage, requires reliable ways to measure the disease. This study compared blood, spinal-fluid, and MRI markers across people who carry a CSF1R mutation but have no symptoms yet, those with symptoms, and healthy volunteers. Several markers tracked with disease severity and brain changes, pointing toward tools that could flag the disease early and monitor it precisely, important for timing treatments like transplantation.

CSF1R-related disorder is a rare, fast-progressing brain disease that varies widely between patients. Because the ApoE gene shapes how the brain's immune cells behave, researchers asked whether it influences this condition. They genotyped 55 patients and reviewed clinical and brain-tissue data. While ApoE variant frequencies matched the general population, carriers of the ApoE4 version had symptom onset and death at notably younger ages and more severe white-matter damage. The findings suggest ApoE4 may act as a modifier of disease course, something worth considering in research and future treatment planning.

A naturally occurring fragment of the CSF1R protein, called "soluble CSF1R," is reduced in the blood of people with CSF1R-ALSP, but its job was unknown. In mouse models of the disease, researchers found that supplying soluble CSF1R eased cognitive and anxiety-like problems. This points to soluble CSF1R as both a possible biomarker and a candidate treatment, an early, preclinical lead that could open a new therapeutic direction for the disease.

This report describes a new family carrying the CSF1R p.R777Q mutation and details how the disease looked clinically and under the microscope, comparing a patient with a short, aggressive course to one with longer-duration disease. With more than 200 CSF1R variants now known, careful descriptions like this connect specific mutations to how the illness behaves, informing diagnosis, genetic counseling, and expectations about the disease's typically rapid progression.

Adult-onset leukoencephalopathy with axonal spheroids (ALSP) is easily mistaken for other neurological conditions, especially when the presentation is unusual. This report describes a 53-year-old woman, with a complex medical history, whose progressive white-matter disease was ultimately identified as ALSP with a previously unreported genetic and imaging pattern. Cases like this widen the recognized spectrum of the disease and reinforce the value of detailed history-taking and timely genetic testing.

Bone-marrow (hematopoietic stem-cell) transplantation is the leading treatment for CSF1R-ALSP, but data have come mostly from scattered single cases. This multicenter study pooled outcomes from 17 adults treated across seven transplant centers internationally, tracking disability, cognition, MRI scores, and the blood marker NfL after transplant. Larger, standardized reports like this are essential for understanding who benefits, how durable the effect is, and how to weigh the procedure's real risks.

Published in Science, this study tackled CSF1R-ALSP at its root, the faulty microglia. Researchers built mice carrying human ALSP-causing mutations, then replaced the defective microglia with healthy cells using a form of bone-marrow transplantation, which eased the disease in the animals. The work provides strong proof-of-concept that swapping out sick microglia for healthy ones can slow this otherwise fatal disease, and helps explain why bone-marrow transplantation benefits patients.

Beyond cognitive and behavioral changes, CSF1R-ALSP often causes movement problems that can confuse the diagnosis. This case series details three genetically confirmed patients (onset ages 41-45) whose movement features included parkinsonism, freezing of gait, cerebellar ataxia, and tremor, alongside cognitive decline. Documenting the range of movement disorders in the disease helps neurologists consider CSF1R-ALSP when patients present with mixed, atypical symptoms, supporting earlier genetic testing and diagnosis.

Most reported CSF1R-ALSP cases come from Asia, Europe, and North America, leaving a gap in understanding how the disease appears in other populations. This study gathered Hispanic patients diagnosed at the Mayo Clinic and centers in Mexico to describe their clinical features. Broadening the picture across ethnic groups helps ensure the disease is recognized worldwide and that genetic testing is offered to everyone who might benefit, regardless of background.

To study how CSF1R mutations damage the human brain, researchers grew "brain organoids", miniature 3D tissue, from the cells of two patients with HDLS (another name for ALSP), alongside gene-corrected control organoids that contained microglia. Comparing the two revealed how the mutant microglia malfunction and harm neighboring neurons. Human-cell models like this, published in eLife, give scientists a realistic platform to dissect the disease and screen potential treatments.

Iluzanebart is the investigational antibody (a TREM2 "agonist") being developed to support microglia in CSF1R-ALSP. This first-in-human Phase 1 study gave single and repeated intravenous doses to 136 healthy volunteers to check basic safety and how the drug behaves in the body before testing it in patients. Establishing that a new drug is safe and well-tolerated in healthy people is the essential first step on the road toward a treatment, and this study cleared that bar.

This review describes two new patients with CSF1R-ALSP from India and pulls together the clinical, MRI, and genetic features of genetically confirmed cases reported worldwide since 2012, comparing Indian, Asian, European, and American patients. Consolidated overviews like this help doctors recognize the disease, which can mimic other dementias, across different populations, and give patients and families a clearer picture of its typical presentation and course.

CSF1R-ALSP is an inherited adult-onset white-matter disease caused by mutations in the CSF1R gene, most of which sit in a region called the tyrosine kinase domain that drives the protein's activity. This Italian report describes a 58-year-old man with early dementia who carried a novel CSF1R change located just outside that domain. Laboratory tests confirmed the variant impairs the protein's function, proving it causes disease. The case shows that harmful mutations can lie outside the usual hotspot and stresses the value of functional testing when interpreting newly found CSF1R variants.

This teaching case describes a 51-year-old woman with subacute worsening of gait and thinking, alongside depression and anxiety, slowed movement, and abnormal muscle stiffness. Her brain MRI showed the frontal white-matter changes and thinning of the corpus callosum typical of an adult-onset leukodystrophy, and genetic testing confirmed a disease-causing CSF1R variant. Notably, she had no relevant family history despite the condition usually being inherited in a dominant pattern. The report helps clinicians recognize CSF1R-related leukoencephalopathy, including cases that arise without an obvious family history.

CSF1R-related disorder is a severe inherited brain disease that is often misdiagnosed at first. This report follows a 52-year-old woman who initially had limb numbness and weakness and was thought to have Parkinson's, a small stroke, or a neck-spine problem. Only as slowed movement and cognitive decline emerged did genetic testing reveal a CSF1R mutation, with MRI showing white-matter changes and small infarcts. Her condition progressed despite treatment. The case underscores how easily this disorder is missed and argues for prompt genetic screening when someone has an unexplained, progressing leukoencephalopathy.

CSF1R-related leukoencephalopathy is a rare adult-onset brain disease, and reports from the Indian subcontinent have been scarce. This series describes four genetically confirmed patients from four Indian families, aged 34 to 40, detailing their symptoms, MRI scans, and gene changes. Most had a rapidly evolving mix of cognitive and behavioral decline with atypical parkinsonism, and each carried a different CSF1R variant. Brain imaging showed the characteristic white-matter and pyramidal-tract involvement. By documenting cases from an underreported population, the study broadens the known genetic and clinical picture of this disorder.

There is no cure for CSF1R-ALSP, which is driven by loss of CSF1R signaling that microglia (the brain's immune cells) need to survive and function. This US study tested a therapeutic idea: because a related receptor, TREM2, uses overlapping signaling, activating TREM2 might compensate for the missing CSF1R activity. The experimental antibody iluzanebart, a TREM2 activator now in development for CSF1R-ALSP, restored the survival of patient-relevant cells in several laboratory models of the disease. These findings support TREM2 activation as a rational treatment strategy and help explain how iluzanebart might work.

CSF1R-related and AARS2-related leukoencephalopathies can look almost identical, clinically, on MRI, and even under the microscope, yet they stem from faults in different genes and are easily confused. Researchers at a Chinese leukoencephalopathy clinic compared 23 CSF1R and 6 AARS2 patients to find distinguishing features. Movement and bulbar problems were more common in CSF1R disease, while ataxia and menstrual or fertility problems pointed toward AARS2. Both showed similar white-matter patterns, but subtle imaging differences helped separate them. This practical guidance helps doctors reach the correct genetic diagnosis sooner, which matters because management differs.

This study gathered 19 newly identified patients from 14 families across the Americas, Asia, Australia, and Europe to show that CSF1R-related disorder occurs worldwide. Importantly for the recessive form, three patients had inherited two altered CSF1R copies and became ill very early, at ages 1, 4, and 22, reflecting the BANDDOS end of the spectrum. The work also examines why some gene carriers stay symptom-free (incomplete penetrance) and traces shared ancestry behind a common mutation, informing genetic counseling for affected families.

CSF1R-BANDDOS is the rare recessive form of CSF1R disease, caused by inheriting two altered copies of the gene (unlike ALSP, which involves one). This report describes three siblings who shared a CSF1R variant and developed developmental delay, treatment-resistant epilepsy, distinctive facial and skeletal features, and, later, in their twenties, neurological decline with brain calcifications and white-matter changes. By documenting the full picture across one family, it expands what doctors know about how BANDDOS presents and progresses.

GeneReviews is a trusted, regularly updated reference written by experts for clinicians and families. This entry covers the whole CSF1R-related disorder spectrum, including the early-onset recessive form (caused by two altered CSF1R copies) that corresponds to BANDDOS. It explains how the diagnosis is confirmed with genetic testing, how symptoms are managed by a multidisciplinary team, which medications to use cautiously, and how the condition is inherited, a practical, plain-language starting point for anyone newly navigating this diagnosis.

As more is learned about diseases caused by CSF1R gene changes, the names and categories used to describe them have become confusing. This paper reviews the genetics, mechanisms, and clinical features across the CSF1R spectrum and proposes clearer terminology. It illustrates the challenge with two patients carrying two CSF1R variants whose features overlap with ALSP but fit a BANDDOS diagnosis, highlighting that the line between the recessive (BANDDOS) and dominant (ALSP) forms is not always sharp.

BANDDOS is the rare recessive CSF1R disease, and published descriptions of it are scarce. This paper adds three new patients and systematically pulls together every previously reported case, 19 people in all, to map how the disease behaves: when symptoms start (often at or soon after birth), the range of neurological and skeletal features, and the CSF1R mutations behind them. It also compares BANDDOS with the more common adult form (CSF1R-ALSP), giving families and clinicians the clearest overview of this ultra-rare condition to date.

BANDDOS occurs when a person inherits two altered copies of the CSF1R gene. This report describes a family in which genetic testing of an affected patient and an affected fetus uncovered a previously unreported homozygous CSF1R change (p.T833M), while unaffected relatives carried only one copy, consistent with recessive inheritance. Laboratory analysis predicted the variant harms the receptor's function. Adding a new disease-causing mutation to the record helps refine genetic diagnosis and counseling for the very few families affected by this condition.

The "dysosteosclerosis" in BANDDOS refers to a pattern of dense, fragile bone. This review explains dysosteosclerosis as an umbrella term now known to arise from several different genes, including CSF1R, and describes the tell-tale X-ray features and how they change with age. It notes that the CSF1R form is distinctive because it also brings brain (extra-skeletal) involvement. For BANDDOS families, it offers helpful background on the bone side of the disease and how doctors tell the various causes apart.

To develop treatments, researchers need laboratory models that reproduce a disease. This review focuses on the two conditions caused by CSF1R faults, the childhood-onset BANDDOS and the adult-onset CSF1R leukoencephalopathy, and asks how well current animal models (mice with Csf1r mutations) mirror what happens in patients. By laying out where the models succeed and fall short, it helps scientists build better systems for studying how CSF1R loss damages the brain and bone, and for testing future therapies.

The CSF1R gene guides microglia (the brain's immune cells) and osteoclasts (bone-remodeling cells), so faults in it can affect both brain and bone. This review traces how one gene produces a spectrum of disease: a single altered copy causes the adult leukoencephalopathy HDLS/ALSP, while two altered copies cause the more severe, earlier-onset BANDDOS, which adds brain malformations and dysosteosclerosis (a dense-bone disorder). It proposes a "dose-dependent" model to explain why the amount of working CSF1R shapes which condition develops.

Only a handful of BANDDOS patients have ever been reported, so each new family teaches doctors something. This report describes three siblings who inherited two copies of a newly identified CSF1R change and showed a mix of skeletal findings and neurological symptoms ranging from mild to severe. Along with a review of earlier cases, it widens the known range of CSF1R mutations and shows how variable the disease can be even within one family, useful context for diagnosis and genetic counseling.