Chediak-Higashi Syndrome
Summary
Clinical characteristics.
Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism, immunodeficiency, and a mild bleeding tendency. Approximately 85% of affected individuals develop the accelerated phase, or hemophagocytic lymphohistiocytosis, a life-threatening, hyperinflammatory condition. All affected individuals including adolescents and adults with atypical CHS and children with classic CHS who have successfully undergone allogenic hematopoietic stem cell transplantation (HSCT) develop neurologic findings during early adulthood.
Diagnosis/testing.
The diagnosis of CHS is established in a proband with giant inclusions within leukocytes on peripheral blood smear and/or by the identification of biallelic pathogenic variants in LYST on molecular genetic testing.
Management.
Treatment of manifestations: Initial chemoimmunotherapy followed by transition to continuation therapy for the accelerated phase; allogenic HSCT as soon as possible to cure hematologic and immunologic defects; L-dopa may be considered for those with parkinsonism; home modifications and intensive rehabilitation for those with ataxia and other neurologic complications; corrective lenses to improve visual acuity; sunglasses to protect sensitive eyes from UV light; sunscreen to prevent sun damage and skin cancer.
Prevention of secondary complications: Prompt aggressive use of antibiotics and antiviral agents for bacterial and viral illnesses; routine inactivated immunizations; intravenous DDAVP prior to invasive procedures to help control bleeding. Platelet transfusions as needed for serious bleeding.
Surveillance: Routine monitoring for chimerism, as 20%-30% donor chimerism is likely enough to protect against reactivation. Yearly ophthalmologic, neurologic, and dermatologic examinations. For atypical or adolescent- or adult-onset CHS: annual abdominal ultrasound examination for hepatosplenomegaly; complete blood count for cytopenias; measurement of serum ferritin concentration and soluble interleukin-2 receptor; and monitoring for liver dysfunction.
Agents/circumstances to avoid: Nonsteroidal anti-inflammatory drugs, which can exacerbate the bleeding tendency; live vaccines.
Genetic counseling.
CHS is inherited in an autosomal recessive manner. When both parents are heterozygous, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal testing of CHS is possible if the pathogenic variants have been identified in the family.
Diagnosis
Suggestive Findings
Diagnosis of Chediak-Higashi syndrome (CHS) should be suspected in individuals with any of the following clinical features and supportive laboratory findings.
Clinical features
- Partial oculocutaneous albinism (OCA); a complete ophthalmologic examination may be necessary to identify the diagnostic finding of reduced iris pigment manifest as iris transillumination or reduced retinal pigmentation.
- A significant history of infections, particularly bacterial infections of the skin and respiratory tract
- Mild bleeding tendency
- Childhood- to early adult-onset neurologic manifestations, including:
- Cognitive impairment
- Peripheral neuropathy
- Ataxia
- Parkinsonism
Supportive laboratory findings
- Giant inclusions in polymorphonuclear neutrophils (PMNs) and (to a lesser extent) in lymphocytes
- This is the most reliable diagnostic criterion for CHS but may be overlooked in a routinely evaluated CBC unless a peripheral smear is reviewed.
- The giant granules are seen using routine staining techniques; however, in some atypical cases, the presence of these giant granules can be somewhat subtle.
- A hematologist, or a clinician experienced in reviewing blood smears for the presence of these giant granules, should review the slide.
- Peroxidase-positive giant inclusions can be seen in leukocytes, megakaryocytes, and other bone marrow precursors (Figure 1c-1e).
- Normal or reduced number of natural killer cells with abnormal (reduced) function
- Neutropenia and impaired neutrophil function (particularly chemotaxis and intracellular bactericidal activity). Note: Immunoglobulins, complement, antibody production, and delayed hypersensitivity are all normal.
- Absent or reduced number and irregular morphology of platelet-dense bodies (required for the secondary wave of platelet aggregation) on whole-mount electron microscopy (Figure 1a, 1b)
- Pigment clumping on polarized light microscopy hair analysis (Figure 1f, 1g).
Figure 1
a. Whole-mount electron microscopy of control platelets shows several dense bodies per platelet (arrows). b. Some CHS platelets have no dense bodies (asterisk) and others have irregular electron-dense granules (arrows).
Note: Because the finding of WBC giant inclusions is the most reliable clinical diagnostic criterion, the combination of any other of the above features should prompt review of a peripheral blood smear evaluating for giant inclusions.
Establishing the Diagnosis
The diagnosis of Chediak-Higashi syndrome is established in a proband with giant inclusions within leukocytes on peripheral blood smear and/or by the identification of biallelic pathogenic variants in LYST on molecular genetic testing (see Table 1).
When the phenotypic and laboratory findings suggest the diagnosis of Chediak-Higashi syndrome, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
- Single-gene testing. Sequence analysis of LYST detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If only one or no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.
- A multigene panel that includes LYST and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
Table 1.
Molecular Genetic Testing Used in Chediak-Higashi Syndrome
| Gene 1 | Method | Proportion of Probands with Pathogenic Variants 2 Detectable by Method |
|---|---|---|
| LYST | Sequence analysis 3 | ~90% |
| Gene-targeted deletion/duplication analysis 4 | Unknown 5 | |
| Unknown 6 | NA |
- 1.
See Table A. Genes and Databases for chromosome locus and protein.
- 2.
See Molecular Genetics for information on allelic variants detected in this gene.
- 3.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
- 4.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
- 5.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
- 6.
Pathogenic variants in other genes are not known to result in CHS. Although it had been previously reported that a lower pathogenic variant detection rate suggested the possibility of locus heterogeneity [Karim et al 2002], the detection method in use was single-strand conformational polymorphism (SSCP) analysis, which has a lower rate of detection than sequencing of the entire open reading frame [Zarzour et al 2005]. However, because the function of the lysosomal trafficking regulator protein encoded by LYST is largely unknown, it is possible that pathogenic variants in other genes whose products interact with LYST could also result in CHS.
Clinical Characteristics
Clinical Description
Chediak-Higashi syndrome (CHS) is characterized by oculocutaneous albinism (OCA), immunodeficiency, and a mild bleeding tendency. Approximately 85% of affected individuals develop the accelerated phase, or hemophagocytic lymphohistiocytosis (HLH), a life-threatening, hyperinflammatory condition. All affected individuals – including adolescents and adults with atypical CHS and children with classic CHS who have successfully undergone allogenic hematopoietic stem cell transplantation (HSCT) – develop neurologic findings.
Partial OCA. Pigment dilution is highly variable, but can involve hair, skin, and eyes. In classic forms of CHS, the hair has a "silvery" or metallic appearance. Skin pigment dilution may not be appreciated unless compared to that of family members. Reduced iris pigmentation may also be subtle, particularly in individuals with darkly pigmented irides. Affected individuals may have decreased retinal pigmentation and nystagmus. Visual acuity varies from normal to moderate impairment. Quantitative data are not available and are difficult to obtain given the young age of individuals with the classic presentation.
OCA was once thought to be a diagnostic criterion for CHS; however, at least two individuals with atypical CHS had no evidence of OCA [Introne et al 2017].
Pigment clumping within the shaft of the hair is generally observed under the light microscope (Figure 1g) [Smith et al 2005].
Immunodeficiency. Frequent infections usually begin in infancy and are often severe in the classic form of this condition. Bacterial infections are most common, with Staphylococcus and Streptococcus species predominating; viral and fungal infections can also occur [Introne et al 1999]. Infections of the skin and upper respiratory tract are the most common. Case reports have identified periodontitis as an important manifestation of immunologic dysfunction [Hart & Atkinson 2007, Khocht et al 2010]. In some instances periodontitis can be the clinical finding leading to correct diagnosis [Bailleul-Forestier et al 2008].
Individuals with atypical CHS may not have a history of unusual or severe infections.
Bleeding tendency. Clinical manifestations are generally mild and include epistaxis, gum/mucosal bleeding, and easy bruising. The bleeding diathesis in CHS may also be subtle (i.e., generally not requiring medical intervention). Bleeding problems may not be listed as a health concern by affected persons.
Accelerated phase. The accelerated phase, occurring in up to 85% of individuals with CHS [Blume & Wolff 1972], can occur at any age. Clinical manifestations include fever, lymphadenopathy, hepatosplenomegaly, anemia, neutropenia, and sometimes thrombocytopenia. Originally thought to be a malignancy resembling lymphoma, the accelerated phase is now known to be HLH characterized by multiorgan inflammation. The accelerated phase and its complications are the most common cause of mortality in individuals with CHS [Eapen et al 2007].
Triggers of the accelerated phase remain unclear. Infection with Epstein-Barr virus is thought to hasten development of the accelerated phase, although this relationship has never been proven. Abnormal function of NK cells and cytolytic T cells is also believed to contribute to development of the accelerated phase [Jessen et al 2011, Gil-Krzewska et al 2016].
Neurologic disease. Despite successful hematologic and immunologic outcomes with allogenic HSCT, neurologic disease still manifests by early adulthood. Findings are the same as those described in untransplanted individuals with atypical or adolescent forms of the disease, but are highly variable and nonspecific [Introne et al 2017].
- Progressive neurologic findings can include:
- Slowly progressive intellectual disabilities
- Sensory or sensorimotor neuropathies and/or a diffuse motor neuronopathy [Lehky et al 2017]
- Balance abnormalities
- Tremor
- Parkinsonism [Bhambhani et al 2013, Weisfeld-Adams et al 2013]
- Spastic paraplegia [Shimazaki et al 2014]
- Neurodegeneration following successful bone marrow transplantation was first described by Tardieu et al [2005] in 11 children who were transplanted at their center.
- All 11 exhibited neurologic manifestations primarily consisting of low cognitive abilities, balance abnormalities and ataxia, tremor, absent deep-tendon reflexes, and motor and sensory neuropathies.
- The authors concluded that the neurologic changes were a result of long-term progression of the disease rather than neurotoxic effects of the transplant-conditioning regimen or the accelerated phase.
Atypical phenotypes. An unknown fraction of individuals with CHS have atypical or milder phenotypes [Karim et al 2002, Westbroek et al 2007], which are likely underrecognized. Some of these affected individuals may be diagnosed after the third decade of life [Weisfeld-Adams et al 2013]. Atypical phenotypes are characterized by the following:
- OCA that is generally subtle or absent
- Insignificant infections or severe infections during childhood that become much less frequent later in life
- Reduced platelet-dense bodies with subtle bleeding manifestations
- In some cases, neurodegeneration (similar to that seen in the classic phenotype) as the predominant manifestation, with only mild alterations in pigmentation, immune function, and bleeding
- Abnormal granules within leukocytes (present in all individuals with an atypical phenotype)
Genotype-Phenotype Correlations
Clinical phenotypes of CHS have been correlated with molecular genotypes [Karim et al 2002, Zarzour et al 2005]:
- In general, loss-of-function variants are associated with severe, childhood-onset form and missense variants with milder adolescent- or adult-onset forms of the disorder [Karim et al 2002, Zarzour et al 2005, Westbroek et al 2007]. However, exceptions have been reported: individuals with biallelic missense variants who present with the severe, childhood-onset form and HLH [Sánchez-Guiu et al 2014].
- It has been shown that the clinical severity of the disease also correlates with the cellular phenotype. Detailed studies of fibroblasts and melanocytes from individuals with CHS with different clinical phenotypes illustrated the range of enlargement of intracellular granule abnormalities in different CHS cell types [Westbroek et al 2007].
Prevalence
Fewer than 500 cases have been reported in the literature [Kaplan et al 2008]. Exact prevalence is difficult to determine as some individuals are reported in the literature more than once. In addition, the phenotypic variability that has more recently been appreciated suggests that many mildly affected individuals may be unrecognized or unreported.
Differential Diagnosis
The diagnosis of Chediak-Higashi syndrome (CHS) should be considered in individuals with pigment dilution defects of the hair, skin, or eyes; congenital or transient neutropenia; immunodeficiency; and otherwise unexplained neurologic abnormalities or neurodegeneration. Each of these findings may be variably represented in affected individuals; therefore, heightened suspicion is needed to pursue an accurate diagnosis.
Oculocutaneous albinism. The seven types of oculocutaneous albinism (OCA type 1, OCA type 2, OCA type 3, OCA type 4, OCA type 5, OCA type 6, and OCA type 7) and OA (ocular albinism) all feature visual impairment and varying degrees of iris/retinal depigmentation. Characteristic skin and hair findings vary from complete absence of pigment to reduced pigment, except in individuals with OA, in whom skin and hair pigment may be normal, and in OCA type 3, which is characterized by bright copper-red hair and lighter tan skin. Neither an infectious history resulting from neutropenia nor neurologic abnormalities accompany the OCA types. OCA is common enough (~1:18,000) that it may coexist with other conditions, including primary immunodeficiencies.
Hermansky Pudlak syndrome (HPS). Like CHS, HPS is an autosomal recessive disorder characterized by OCA and a bleeding diathesis secondary to absent platelet-dense bodies. Of the at least ten subtypes of HPS, HPS2 (caused by biallelic pathogenic variants in AP3B1) most closely resembles CHS.
HPS2 has been reported in at least 30 individuals [Jessen et al 2013; Huizing et al, unpublished] (see Hermansky-Pudlak Syndrome). In addition to the albinism and bleeding diathesis, individuals with HPS2 also have congenital neutropenia, a recurrent pattern of severe bacterial infections, and pulmonary fibrosis. Patients with HPS2 are at risk for HLH, although the risk is less than for CHS and GS. The distinction between CHS and HPS2 depends on identifying giant intracellular granules within the neutrophils of those individuals with CHS.
Griscelli syndrome (GS) (OMIM PS214450). Mild skin hypopigmentation and silvery gray hair are present, but platelet function is normal. Griscelli syndrome may be caused by biallelic pathogenic variants in:
- MYO5A (GSI), characterized by severe neurologic involvement [Pastural et al 1997];
- RAB27A (GSII), leading to immunodeficiency and lymphohistiocytosis [Ménasché et al 2000]; and
- MLPH (GSIII), with hypopigmentation as its only clinical characteristic [Ménasché et al 2003].
Cross syndrome (OMIM 257800). Cross syndrome is characterized by hypopigmentation, ocular defects, and severe developmental delay reflecting extensive central nervous system involvement. An infectious component is absent from this diagnosis.
Immunodeficiency due to defect in MAPBP-interacting protein (OMIM 610798) is a novel immunodeficiency syndrome identified in four members of a Mennonite pedigree [Bohn et al 2007]. Clinical features include partial albinism, short stature, congenital neutropenia, and lymphoid deficiency. Neutrophils show altered azurophilic granule ultrastructure and less than normal microbicidal function of phagosomes, in contrast to the giant inclusions seen in neutrophils in CHS. Neurologic dysfunction was not described in members of this pedigree. Biallelic pathogenic variants in LAMTOR2 are causative; inheritance is autosomal recessive.
Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by proliferation and infiltration of hyperactivated macrophages and T-lymphocytes manifesting as acute illness with prolonged fever, cytopenias, and hepatosplenomegaly. Onset is typically within the first few months of life and, on occasion, in utero, although later childhood or adult onset is more common than previously suspected. Neurologic abnormalities that may be present initially or may develop later include: increased intracranial pressure, irritability, neck stiffness, hypotonia, hypertonia, convulsions, cranial nerve palsies, ataxia, hemiplegia, quadriplegia, blindness, and coma. Rash and lymphadenopathy are less common. Other findings include liver dysfunction and bone marrow hemophagocytosis. The median survival of children with typical FHL, without treatment, is less than two months; progression of hemophagocytic lymphohistiocytosis and infection account for the majority of deaths in untreated individuals. Familial HL, inherited in an autosomal recessive manner, is caused by biallelic variants in PRF1, STX11, STXBP2, or UNC13D.
Vici syndrome (OMIM 242840). A small number of individuals with cutaneous hypopigmentation, combined immunodeficiency, agenesis of the corpus callosum, bilateral cataracts, and cleft lip and palate have been described. Cognitive impairment, seizures, and severe respiratory infections were observed [Dionisi Vici et al 1988, del Campo et al 1999, Chiyonobu et al 2002, Miyata et al 2007]. Biallelic pathogenic variants in EPG5 are causative; inheritance is autosomal recessive.
Management
Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Chediak-Higashi syndrome (CHS), the evaluations detailed in Table 2 (if not already completed) are recommended.
Table 2.
Recommended Evaluations Following Initial Diagnosis in Individuals with Chediak-Higashi Syndrome
| System/Concern | Evaluation | Comment |
|---|---|---|
| Hematologic |
| To assess for evidence of the accelerated phase 4 |
| Immunologic | Screening for history of frequent or unusual infections | Referral to immunologist &/or hematologist as needed |
| Gastrointestinal | Serum triglyceride concentration | To assess for liver dysfunction 5 |
| Fibrinogen level | ||
| Neurologic | Complete neurologic eval | |
| Consideration of lumbar puncture | To assess for evidence of hemophagocytosis in cerebrospinal fluid | |
| Ocular | Ophthalmology eval | For signs of ↓ pigment & refractive errors |
| Other | Consultation w/clinical geneticist &/or genetic counselor |
- 1.
For evidence of cytopenia involving at least two cell lines
- 2.
Elevated serum ferritin and soluble interleukin-2 receptor level are associated with the accelerated phase.
- 3.
To assess for hemophagocytosis
- 4.
Filipovich [2006]
- 5.
Hypertriglyceridemia and hypofibrinogenemia are suggestive of liver dysfunction, which can be associated with the accelerated phase.
Treatment of Manifestations
Table 3.
Treatment of Manifestations in Individuals with Chediak-Higashi Syndrome
| Manifestation/ Concern | Treatment | Considerations/Other |
|---|---|---|
| Hematologic & immunologic defects | Guidelines for treatment of accelerated phase same as for familial hemophagocytic lymphohistiocytosis (HLH). 1, 2, 3, 4 |
|
| Hematopoietic stem cell transplantation (HSCT) 5, 6, 7, 8 |
| |
| Parkinsonism | Trial of L-dopa therapy 9 | |
| Ataxia |
| Treatment is best provided by a multidisciplinary team comprising a neurologist, physiatrist, PTs, & OTs. |
| Refractive errors &/or light sensitivity |
| Referral to ophthalmologist |
| Skin hypopigmentation | Sunscreen | To prevent sun damage & skin cancer |
OT = occupational therapist; PT = physical therapist/therapy
- 1.
Better HLH control at the time of HSCT leads to better long-term outcome.
- 2.
Recent evaluation of HLH-2004 protocol did not find statistical evidence for superiority over the HLH-94 regimen; therefore, HLH-94 remains the standard of care [Bergsten et al 2017].
- 3.
The remission induction rate may be as high as 71% when considering all heritable causes of HLH [Filipovich & Chandrakasan 2015].
- 4.
This treatment is also effective at inducing remission in CHS so that HSCT can be performed [Trottestam et al 2009].
- 5.
This is the only treatment that cures the hematologic and immunologic deficits.
- 6.
The conditioning regimen is at the discretion of the treatment center; however, reduced-intensity conditioning regimens have demonstrated improved survival over traditional myeloablative protocols.
- 7.
Although not specific for CHS, in a cohort of 40 individuals with genetic forms of HLH including CHS, the three-year post-HSCT survival was 92% following reduced-intensity conditioning regimens [Marsh et al 2010].
- 8.
The overall five-year survival rate in 35 children with CHS who underwent HSCT was 62% [Eapen et al 2007].
- 9.
Bhambhani et al [2013], Introne et al [2017]
Prevention of Secondary Complications
Table 4.
Prevention of Secondary Complications in Individuals with Chediak-Higashi Syndrome
| Manifestation/ Concern | Prevention | Considerations/Other |
|---|---|---|
| Infection | Inactivated vaccine administration according to typical schedule |
|
| Antibiotic & antiviral agents should be used promptly & aggressively for bacterial & viral illnesses, respectively. | Consideration of prophylactic antibiotics in those w/recurrent infections 2, 3 | |
| Bleeding tendency | Intravenous DDAVP (0.2-0.4 µg/kg/dose over 15-30 mins) 30 mins prior to invasive procedures | For serious trauma or extensive bleeding, platelet transfusion may be necessary. |
| Skin cancer | Sunscreen (See Treatment of Manifestations.) |
- 1.
Principi & Esposito [2014], Sobh & Bonilla [2016]
- 2.
McCusker & Warrington [2011]
- 3.
For individuals with compromised immune systems and neutropenia who will be undergoing invasive dental procedures or procedures that cause significant bleeding, prophylaxis should be considered [AAPD reference manual].
Surveillance
No consensus guidelines for surveillance of classic CHS exist. Generally, evaluation for bone marrow transplantation is initiated after the diagnosis is confirmed (see Treatment of Manifestations).
Table 5.
Recommended Surveillance for Individuals with Chediak-Higashi Syndrome
| System/Concern | Evaluation | Frequency |
|---|---|---|
| Hematologic | Monitoring of chimerism 1, 2 | Routine |
| Neurologic | Neurologic exam | At least annually |
| Ocular | Ophthalmologic exam | |
| Skin | Dermatologic exam 3 |
- 1.
Especially in those who undergo HSCT with reduced-intensity conditioning as the incidence of mixed chimerism in the bone marrow is higher than in those who undergo traditional conditioning.
- 2.
Recent studies suggest 20%-30% donor chimerism is likely enough to protect against reactivation [Hartz et al 2016].
- 3.
For routine monitoring in the setting of hypopigmentation
Table 6.
Additional Recommended Surveillance for Individuals with Atypical or Adult-Onset Chediak-Higashi Syndrome
| System/Concern | Evaluation | Frequency 1 |
|---|---|---|
| Hematologic | Abdominal ultrasound 2 | At least annually |
| Complete blood count 3 | ||
| Ferritin concentration 4 | ||
| Soluble interleukin-2 receptor level 4 | ||
| Serum triglyceride concentration 5 | ||
| Fibrinogen level 6 | ||
| Consideration of bone marrow biopsy | If history, physical exam, or lab findings suggest the accelerated phase |
- 1.
The frequency listed can be modified based on changes in clinical status.
- 2.
To monitor for hepatosplenomegaly
- 3.
To evaluate for cytopenias
- 4.
Elevated serum ferritin and soluble interleukin-2 receptor level are associated with the accelerated phase.
- 5.
Elevated levels may be a sign of liver dysfunction.
- 6.
Low levels may be a sign of liver dysfunction.
Agents/Circumstances to Avoid
All nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., aspirin, ibuprofen) are to be avoided as they can exacerbate the bleeding tendency. Live vaccines should also be avoided.
Evaluation of Relatives at Risk
It is appropriate to evaluate the older and younger sibs of a proband as early as possible. Early diagnosis may provide the opportunity to perform HSCT prior to the development of the accelerated phase.
- If the family-specific pathogenic variants are known, molecular genetic testing can be used to clarify the genetic status of at-risk sibs.
- If the pathogenic variants in the family are not known, examination of peripheral blood for the presence of giant inclusions within white blood cells can be used to clarify the disease status of at-risk sibs.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
Pregnancy Management
In the limited cases of pregnancy in females with CHS reported in the literature [Price et al 1992, Weisfeld-Adams et al 2013], presence of the disease had no impact on the pregnancy, labor, or delivery. The infants were normal. The pregnancy also did not appear to affect the course of disease in the affected mothers.
Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.