Kmt2b-Related Dystonia
Summary
Clinical characteristics.
KMT2B-related dystonia (DYT-KMT2B) is a complex childhood-onset (mean age 7 years) movement disorder described to date in 39 individuals. It is characterized by a progressive disease course evolving commonly from lower-limb focal dystonia into generalized dystonia with prominent cervical, cranial, and laryngeal involvement. Communication difficulties, secondary to articulation difficulties and low speech volume, are common. Bulbar dysfunction leads to impaired swallowing. Intellectual disability (ID) / developmental delay (DD) are commonly reported.
Additional findings can include eye movement abnormalities, skin changes, psychiatric comorbidities (attention-deficit/hyperactivity disorder, anxiety, depression, and obsessive-compulsive disorder), myoclonus, seizures, spasticity, and sensorineural hearing loss. Many affected individuals follow a similar disease course, though milder and atypical findings have been described.
Diagnosis/testing.
The diagnosis of DYT-KMT2B is established in a proband with either a heterozygous pathogenic variant in KMT2B or a heterozygous interstitial deletion of 19q13.12 that includes a KMTB2 whole-gene deletion.
Management.
Treatment of manifestations:
- Dystonia: Although pharmacologic treatment with levodopa and other commonly used anti-dystonic agents generally does not result in long-term benefit for the majority of patients, a trial of these agents is considered reasonable. One group observed a significant improvement of motor manifestations with an antimuscarinic (anticholinergic) agent. Bilateral globus pallidus interna deep brain stimulation results in substantial clinical improvement, particularly in younger patients.
- Other: Early initiation of physiotherapy and a tailored exercise program is advised as well as use of adaptive aids (e.g., ankle-foot orthoses, walkers) as necessary to support and maintain ambulation. Speech and language therapy is crucial to assist in feeding skills and communication. Nutrition specialists / dieticians are needed to assess calorie needs and reduce the risk of malnutrition. Address DD/ID issues through appropriate specialists/agencies.
Surveillance: Regular monitoring of weight and height in children, nutritional status, swallowing function, speech and language, adaptive functioning (ability to perform activities of daily living), orthopedic complications (hip dislocation and kyphoscoliosis), hearing, eye movements, skin, and psychiatric status.
Genetic counseling.
DYT-KMT2B is inherited in an autosomal dominant manner. To date, ~84% of individuals have the disorder as the result of a de novo KMT2B pathogenic variant and ~16% have inherited the KMT2B variant (10% from an affected parent; 6% from a clinically asymptomatic parent). Each child of an individual with DYT-KMT2B has a 50% chance of inheriting the KMT2B pathogenic variant; reduced penetrance and intrafamilial clinical variability have been reported. Once the KMT2B pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
Diagnosis
No formal diagnostic criteria for DYT-KMT2B have been published to date.
Suggestive Findings
DYT-KMT2B should be suspected in individuals with the following findings.
Clinical Findings
Typical disease course [Zech et al 2016, Lange et al 2017, Meyer et al 2017, Zech et al 2017a, Zech et al 2017b]:
- Onset of dystonia usually within the first decade, but may be in the second decade or later
- Initial presentation:
- In the majority, lower-limb dystonia (manifesting as toe-walking, abnormal gait, and balance difficulties)
- In some, upper-limb dystonia, and less commonly, cervical or truncal dystonia
- With increasing age: prominent cervical, laryngeal, and/or cranial dystonia (manifesting as retrocollis, torticollis, dysarthria/anarthria, dysphonia, and difficulties in swallowing and chewing)
- Within two to 11 years of onset: evolution into generalized dystonia
Neuroimaging
Brain MRI abnormalities frequently reported in younger affected individuals (age range: 3-18 years) include subtle and symmetric hypointense lateral streaks in the external globus pallidus (Figure 1) on T2-weighted, T2*-weighted, susceptibility-weighted, and echo-planar b0-diffusion imaging data sets [Meyer et al 2017].
Figure 1.
Radiologic MRI features of patients with KMT2B variants a-l. T2*-weighted (a, d) and T2-weighted (b, c) images; echo-planar technique diffusion imaging data set images with b value of zero (e-h); susceptibility-weighted sequences (i-l)
Note: This pattern may represent an age-dependent phenomenon as these features were often not evident in adults and may become less prominent over time. Indeed, in one individual such MR changes were less evident on MRI performed at age 17 years compared to neuroimaging performed at age 13 years.
DaTSCAN and FDG-PET-CT scan were normal in the three individuals evaluated with these methods.
Laboratory Findings
CSF analysis in 13 affected individuals showed the following minor perturbations of monoaminergic metabolites [Meyer et al 2017]:
- Marginal reduction of 5-hydroxyindoleacetic acid (5-HIAA) in three
- Mild elevation of 5-HIAA and tetrahydrobiopterin (BH4) in two others
Establishing the Diagnosis
The diagnosis of DYT-KMT2B is established in a proband with one of the following [Zech et al 2016, Lange et al 2017, Meyer et al 2017, Zech et al 2017a, Zech et al 2017b] (see Table 1):
- A heterozygous pathogenic variant in KMT2B (26/36 probands reported to date)
- A heterozygous interstitial deletion of 19q13.12 that encompasses the entirety of KMTB2 (10/36 probands reported to date)
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (chromosomal microarray analysis, genomic sequencing, exome array) depending on the phenotype.
Persons with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom a specific diagnosis has been elusive are more likely to be diagnosed using comprehensive genomic testing (see Option 2).
Option 1
When the phenotypic and neuroimaging findings suggest the diagnosis of DYT-KMT2B, molecular genetic testing approaches can include chromosomal microarray analysis (CMA) (if not already performed) followed by gene-targeted testing (single-gene testing or a dystonia multigene panel):
- CMA uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications of 19q13.12 (including KMT2B) that cannot be detected by sequence analysis.
- Single-gene testing. Sequence analysis of KMT2B 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 no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.
- A dystonia multigene panel that includes KMT2B 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 this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1).For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
Option 2
When the phenotype is indistinguishable from many other inherited disorders with dystonia, comprehensive genomic testing (which does not require the clinician to determine which gene is likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible. Exome array (when clinically available) may be considered if exome sequencing is not diagnostic, particularly when evidence supports autosomal dominant inheritance.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
Table 1.
Molecular Genetic Testing Used in KMT2B-Related Dystonia
| Gene 1 | Method | Proportion of Probands with a Pathogenic Variant 2 Detectable by Method |
|---|---|---|
| KMT2B | Sequence analysis 3 | 26/36 4, 5 |
| Gene-targeted deletion/duplication analysis 6 | Unknown (no data available) | |
| CMA 7 | 10/36 4, 8 |
- 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.
Meyer et al [2017]
- 5.
Zech et al [2016], Lange et al [2017], Zech et al [2017a] (this paper includes two variants of uncertain significance), Zech et al [2017b]
- 6.
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.
- 7.
Chromosomal microarray analysis (CMA) using oligonucleotide arrays or SNP arrays identifies deletion of 19q13.12.
- 8.
Dale et al [2012]
Clinical Characteristics
Note: Except where indicated, information in this section is based on Zech et al [2016], Lange et al [2017], Meyer et al [2017], Zech et al [2017a], Zech et al [2017b], and Gorman et al [2018].
Clinical Description
KMT2B-related dystonia (DYT-KMT2B) is a complex childhood-onset movement disorder. It typically presents with a progressive disease course evolving commonly from lower-limb focal dystonia into generalized dystonia with prominent cervical, cranial, and laryngeal involvement. Additional neurologic, psychiatric, and systemic features are commonly reported. Many affected individuals follow a similar disease course, though milder and atypical cases have been described.
DYT-KMT2B has been recently described in 36 probands. Of these, one proband had an affected mother and another had a similarly affected father and grandfather (total 39 individuals reported).
Disease onset typically occurs between ages one and 10 years (33/39 individuals); however, onset in the second decade was reported in five individuals for whom data were available. Mean age of onset was 7.05 years in 38 individuals for whom data were available.
Presenting manifestations (documented for 37/39 individuals) include the following:
- Lower-limb dystonia characterized by foot posturing, toe walking, and gait disturbance (in 28 individuals)
- Upper-limb dystonia leading to abnormal hand/arm posturing, dystonic tremor, and difficulties in handwriting and hand dexterity (6)
- Cervical dystonia (1)
- Truncal/axial dystonia (1)
- Dystonic tremor and (action) myoclonus (1)
Over time, the majority of individuals developed progressive cranial, cervical, and laryngeal dystonia with features of retrocollis, torticollis, dysarthria/anarthria, dysphonia, and difficulties in swallowing and chewing.
Affected individuals often have communication difficulties, secondary to articulation difficulties and low speech volume.
Bulbar dysfunction leads to impaired swallowing, which can cause substantial morbidity due to the risk of aspiration pneumonia. A few individuals with DYT-KMT2B have required gastrostomy insertion for feeding difficulties.
Generalized dystonia becomes evident in most individuals (34/39) within two to 11 years of initial presentation. The level of gross motor disability comprises a broad spectrum ranging from minor gait disturbance to wheelchair dependence (GMFCS II-V).
Developmental delay, described in 16 of 39 affected individuals, usually precedes the onset of dystonia and is thought to be non-progressive. Eight presented with neurodevelopmental delay, seven had isolated speech delay, and one had only delay in attainment of fine motor skills.
Mild cognitive impairment was reported in 21 of 39 affected individuals, most of whom developed variable degrees of functional independence in adolescence and adulthood.
Life expectancy is not known, but individuals in the seventh decade of life with DYT-KMT2B have been reported [Zech et al 2016].
Additional clinical features of DYT-KMT2B included the following (note that 9 individuals had >1 additional clinical feature):
- Eye movement abnormalities including strabismus, astigmatism, delay in saccade initiation, hypometric vertical saccades, oculomotor apraxia (in 8 individuals)
- Dermatologic features of ectodermal dysplasia including cutis aplasia, sparse hair, sparse to absent eyelashes or brows, hypertrichosis, and ichthyotic skin with criss-cross pattern under the feet and at the knees (5). Although broad postsurgical scarring and "phimosis" have been reported, it is not currently known if these features are incidental or truly disease related. Future identification of further individuals with molecularly confirmed DYT-KMT2B may better clarify these associations.
- Psychiatric comorbidities including attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, and obsessive-compulsive disorder (3)
- Myoclonus (3)
- Microcephaly (3)
- Seizures (2), including one with absence seizures
- Spasticity (1)
- Sensorineural hearing loss (1)
- Subtle dysmorphic features that may include an elongated face and bulbous nasal tip [Zech et al 2016, Meyer et al 2017, Zech et al 2017a, Zech et al 2017b]
The following atypical DYT-KMT2B disease manifestations [Meyer et al 2017] are rarely reported:
- Paroxysmal cervical dystonia, reported in one individual. Notably, the mother of this proband, who was found to harbor this KMT2B variant, had onset of symptoms in early adulthood. She developed gait abnormalities, a progressive inability to run, and periodic paroxysmal upper-limb and neck dystonia.
- Solely oromandibular features without clinical evidence of limb dystonia
Genotype-Phenotype Correlations
Meyer and colleagues [2017] reported statistically significant earlier disease onset in individuals with DYT-KMT2B with loss-of-function variants (e.g., interstitial deletions; frameshift, splice site, and stop-gain variants) compared to those with missense variants. However, genotype does not appear to influence the rate of disease progression, disease severity, or clinical response to deep brain stimulation.
Early neurodevelopmental delay was reported in 5/10 individuals with a heterozygous 19q13.12 contiguous gene deletion, compared to 11/29 with intragenic KMT2B pathogenic variant. Likewise, the majority of individuals (8/10) with a heterozygous 19q13.12 contiguous gene deletion had mild cognitive impairment, compared to 13/29 with an intragenic KMT2B pathogenic variant. Identification of additional individuals with DYT-KMT2B will determine if this is a true genotype-phenotype correlation.
Penetrance
DYT-KMT2B is postulated to show reduced penetrance as asymptomatic heterozygotes have been identified. Although parental status is not always known, to date two (6%) of 32 reported pathogenic variants have been inherited from a seemingly unaffected parent [Meyer et al 2017].
Gender differences have not been observed to date.
Prevalence
Disease prevalence is not yet established. To date, 39 individuals (from 36 families) with DYT-KMT2B have been described.
Differential Diagnosis
Table 2.
Disorders Associated with Complex Early-Onset Generalized Dystonia to Consider in the Differential Diagnosis of KMT2B-Related Dystonia
| Disorder | Gene(s) | MOI | Additional Overlapping Clinical Features | Distinguishing Features of Differential Diagnosis Disorder | ||
|---|---|---|---|---|---|---|
| Clinical | MRI | Laboratory Findings | ||||
| Inherited forms of dystonia 1 | ||||||
| DYT-TOR1A (DYT1) | TOR1A | AD | Isolated dystonia w/less prominent cervical/cranial/bulbar features early in disease course | |||
| DYT-THAP1 (DYT6) | THAP1 | AD | Early craniofacial involvement & laryngeal dystonia | Isolated dystonia w/older average age of onset | ||
| DYT-PRKRA (DYT16) | PRKRA | AR | Mild parkinsonism | |||
| Early-onset NBIA disorders 2 | ||||||
| PKAN | PANK2 | AR |
| Characteristic T2-weighted hypointensity in globus pallidus & substantia nigra | ||
| PLAN | PLA2G6 | AR | ||||
| MPAN | C19orf12 | AR | ||||
| BPAN | WDR45 | XL | ||||
| FAHN | FA2H | AR | ||||
| Kufor-Rakeb syndrome | ATP13A2 | AR | ||||
| CoPAN | COASY | AR | ||||
| Disorders of heavy metal metabolism | ||||||
| Wilson disease | ATP7B | AR | Psychiatric comorbidities |
| Face-of-the-giant-panda sign |
|
| SLC39A14 deficiency | SLC39A14 | AR |
| T1-weighted hyperintensities & T2-weighted hypointensities in basal ganglia & anterior pituitary gland, cerebellum, dorsal pons, spinal cord | Hypermanganesemia | |
| Dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease | SLC30A10 | AR |
| T1-weighted hyperintensities in basal ganglia |
| |
| Neurotransmitter disorders | ||||||
| Sepiapterin reductase deficiency | SPR | AR | Hypotonia |
| Reduced tracer uptake on DaTSCAN images (DTDS) | CSF neurotransmitter abnormalities |
| GTPCH1 deficiency (OMIM 233910) | GCH1 | AR | ||||
| Tyrosine hydroxylase deficiency | TH | AR | ||||
| Aromatic L-amino acid decarboxylase deficiency (OMIM 608643) | DDC | AR | ||||
| Brain serotonin-dopamine deficiency [Rilstone et al 2013] | SLC18A2 | AR | ||||
| SLC6A3-related dopamine transporter deficiency syndrome | SLC6A3 | AR | ||||
| Mitochondrial disorders | ||||||
| Mitochondrial cytopathies | See footnote 3 | AD AR Mat | Multisystemic involvement |
|
| |
| POLG-related disorders | POLG | AR | ||||
| Other inherited metabolic disorders | ||||||
| Alpha-fucosidosis (OMIM 230000) | FUCA1 | AR |
| |||
| Glutaric acidemia type 1 (OMIM 231670) | GCDH | AR |
|
|
| |
| Methylmalonic acidemia, late-onset (See Isolated Methylmalonic Acidemia.) | MCEE MMAA MMAB MMADHC MUT | AR | Hypotonia; psychiatric symptoms |
|
| |
| Propionic acidemia, late-onset | PCCA PCCB | AR |
|
| ||
| Niemann-Pick disease type C | NPC1 NPC2 | AR |
| ↑ oxysterol levels | ||
| GM1 gangliosidosis, type III (See GLB1-Related Disorders.) | GLB1 | AR |
| |||
| Lesch-Nyhan syndrome | HPRT1 | XL |
| Hyperuricemia | ||
| Other monogenic disorders with prominent dystonia phenotype | ||||||
| ADCY5-related movement disorder | ADCY5 | AD | Hypotonia |
| ||
| Rapid-onset dystonia-parkinsonism (See ATP1A3-Related Neurologic Disorders.) | ATP1A | AD |
| ↓ tracer uptake on DaTSCAN images | ||
| Juvenile-onset Parkinson disease (See Parkinson Disease Overview.) | DNAJC6 FBX07 PARK7 (DJ1) PINK1 PRKN (PARK2) | AR | ||||
| Young-onset dystonia-parkinsonism (DYT16) [Camargos et al 2008] | PRKRA | AR | ||||
| TUBB4A-related leukodystrophy (H-ABC) | TUBB4A | AD |
|
| ||
| Deafness-dystonia-optic neuronopathy syndrome | TIMM8A | XL | ||||
| Pyruvate carboxylase deficiency | PC | AR | ||||
AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; Mat = maternal inheritance; MOI = mode of inheritance; XL = X-linked
- 1.
See Hereditary Dystonia Overview.
- 2.
See Neurodegeneration with Brain Iron Accumulation Disorders Overview.
- 3.
Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutation of genes encoded by either nuclear DNA or mitochondrial DNA.
Management
Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with DYT-KMT2B, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:
- Complete detailed neurologic examination to delineate movement disorder phenotype (dystonia, myoclonus, spasticity)
- Consider early assessment for possible effectiveness of deep brain stimulation
- Physiotherapy, occupational therapy, and speech and language therapy assessment
- Evaluation of swallowing safety (videofluoroscopy may be needed)
- Nutritional evaluation to ensure adequate calorie intake
- Developmental assessment / IQ testing
- Orthopedic examination for secondary complications including fixed contractures, joint dislocation, and/or kyphoscoliosis
- Ophthalmologic examination including assessment of vision and eye movements
- Assessment of hearing
- Formal neuropsychiatric testing
- Dermatologic examination
- Consultation with a clinical geneticist and/or genetic counselor
Treatment of Manifestations
Dystonia. Although pharmacologic treatment with levodopa and other commonly used anti-dystonic agents (e.g., trihexiphenidyl, baclofen, gabapentin, tetrabenazine, benzodiazepines) has not proven to result in long-term benefit for the majority of patients with DYT-KMT2B [Zech et al 2016, Meyer et al 2017, Zech et al 2017a], a trial of these anti-dystonia agents would be considered reasonable. Lange and colleagues [2017] observed a significant improvement of motor manifestations on treatment with an antimuscarinic (anticholinergic) agent.
Bilateral globus pallidus interna deep brain stimulation (DBS) results in substantial clinical improvement, particularly in younger patients, and should be considered as a possible therapeutic route for patients with DYT-KMT2B based on the following results [Zech et al 2016, Meyer et al 2017, Zech et al 2017a, Zech et al 2017b]:
- Three patients regained independent ambulation.
- Five patients demonstrated sustained clinical effect at eight years following implantation.
Early initiation of physiotherapy and a tailored exercise program is essential to maintain function and prevent secondary orthopedic complications such as joint contractures, hip dislocation, and/or kyphoscoliosis.
Adaptive aids (e.g., ankle-foot orthoses, walkers) should be supplied to support and maintain ambulation.
Speech and language therapy is crucial to assist in feeding skills and communication. Some patients may need communication devices.
Nutrition specialists / dieticians are of utmost importance to assess calorie needs and reduce the risk of malnutrition.
Videofluoroscopy can be used to evaluate the risk of aspiration and assess the need for alternative means of feeding.
For patients with respiratory compromise from chest deformities related to scoliosis, prophylactic antibiotics during the winter months, regular physiotherapy, and influenza immunizations should be considered due to the increased risk of pulmonary infections.
Developmental Delay / Intellectual Disability Management Issues
The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.
Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a federally funded program available in all states.
Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed.
Ages 5-21 years
- In the US, an IEP based on the individual's level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21.
- Discussion about transition plans including financial, vocation/employment, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood.
All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life.
Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
In the US:
- Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
- Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.
Motor Dysfunction
Gross motor dysfunction
- Physical therapy is recommended to maximize mobility.
- Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).
Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.
Oral motor dysfunction. Assuming that the individual is safe to eat by mouth, feeding therapy, typically from an occupational or speech therapist, is recommended for affected individuals who have difficulty feeding due to poor oral motor control.
Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties.
Social/Behavioral Concerns
Children may qualify for and benefit from interventions such as applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and is typically performed one on one with a board-certified behavior analyst.
Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications (e.g., medication used to treat ADHD) when necessary.
Surveillance
Surveillance includes regular monitoring of the following:
- Weight and height using age-appropriate and gender-matched growth charts in children
- Nutritional status to evaluate dietary requirements
- Swallowing to evaluate risk for aspiration
- Speech and language regarding needs for augmentative communication
- Adaptive functioning (ability to perform activities of daily living)
- Potential orthopedic complications (e.g., hip dislocation and kyphoscoliosis with hip and spine x-rays every 6 to 12 months)
- Hearing
- Strabismus and refractive errors
- Skin examination for changes requiring appropriate management
- Psychiatric status
Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
Pregnancy Management
Before conception, counseling on the potential effects of antidystonic medications on the pregnancy and developing fetus should be discussed and an appropriate plan on managing medications during pregnancy should be established. Pregnant women with DYT-KMT2B should also be advised about the induction of dystonic side effects of antiemetics [Nageshwaran et al 2011].
Data on the use of antidystonic agents in pregnancy are scarce. Although single case reports of medical treatment with trixhexyphenidyl, levodopa/carbidopa, and clonazepam during pregnancy have not observed adverse effects on the affected mother or the fetus [Watanabe et al 2009, Mendhekar & Andrade 2011, Nageshwaran et al 2011, Robottom & Reich 2011, Serikawa et al 2011, Watanabe & Matsubara 2012, Dostal et al 2013], oral medications may be preferably tapered to the lowest effective dose.
Treatment with DBS has been reported in a series of cases with implantation prior to conception [Scelzo et al 2015, Ziman et al 2016, Park et al 2017]. No adverse effects on the affected mother and the fetus have been reported to date.
See MotherToBaby for further information on medication use during pregnancy.
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.