Koolen-De Vries Syndrome
Summary
Clinical characteristics.
Koolen-de Vries syndrome (KdVS) is characterized by developmental delay / intellectual disability, neonatal/childhood hypotonia, dysmorphisms, congenital malformations, and behavioral features. Psychomotor developmental delay is noted in all individuals from an early age. The majority of individuals with KdVS function in the mild-to-moderate range of intellectual disability. Other findings include speech and language delay (100%), epilepsy (~33%), congenital heart defects (25%-50%), renal and urologic anomalies (25%-50%), and cryptorchidism (71% of males). Behavior in most is described as friendly, amiable, and cooperative.
Diagnosis/testing.
The diagnosis of Koolen-de Vries syndrome is established in a proband who has either a heterozygous 500- to 650-kb deletion at chromosome 17q21.31 that includes KANSL1 or a heterozygous intragenic pathogenic variant in KANSL1. Note: The 17q21.31 deletion cannot be identified by analysis of G-banded chromosomes or other cytogenetic banding techniques.
Management.
Treatment of manifestations: Physiotherapy for gross and fine motor delays; speech therapy to support early feeding challenges and communication development; educational programs directed to specific disabilities identified. Routine treatment of: vision issues / strabismus; hearing loss; cardiac, renal, and urologic problems; epilepsy; scoliosis, hip dislocation, and positional deformities of the feet; multiple nevi.
Surveillance: Routine ophthalmologic examinations for hypermetropia and strabismus; monitoring for progressive spine deformities; routine monitoring for other medication complications depending on the organ system involved.
Genetic counseling.
Koolen-de Vries syndrome, caused by a deletion at 17q21.31 or a pathogenic variant in KANSL1, is inherited in an autosomal dominant manner; to date almost all cases result from a de novo deletion or KANSL1 pathogenic variant. Thus, most affected individuals represent simplex cases (i.e., a single occurrence in a family). The recurrence risk for future pregnancies is low (probably <1%) but greater than that of the general population because of the possibility of germline mosaicism in one of the parents. Prenatal testing is technically feasible, but the likelihood of recurrence in families who have had an affected child is low.
Diagnosis
Suggestive Findings
Koolen-de Vries syndrome (KdVS) should be suspected in individuals presenting with mild-to-moderate developmental delay or intellectual disability in which speech and language development is particularly affected, in combination with additional clinical findings.
Additional clinical findings
- Neonatal/childhood hypotonia and feeding difficulties
- Epilepsy
- Dysmorphic facial features (see Clinical Description and Figure 1)
- Hypermetropia
- Congenital heart anomalies
- Congenital renal/urologic anomalies
- Hypermobility of the joints and/or joint dislocation/dysplasia
- Deformities of the spine and/or feet
Figure 1.
Photographs of eight individuals with a 17q21.31 deletion
Establishing the Diagnosis
The diagnosis of Koolen-de Vries syndrome is established in a proband with typical clinical findings and detection of any of the following (see Table 1):
- A heterozygous deletion at chromosome 17q21.31 that includes KANSL1 (~95% of affected individuals) [Koolen et al 2006, Sharp et al 2006, Shaw-Smith et al 2006]. The 17q21.31 deletion is typically 500- to 650-kb in size (hg19: chr17:43,700,000-44,250,000) and is flanked by segmental duplications.
- A heterozygous intragenic pathogenic variant in KANSL1 (~5% of affected individuals) [Koolen et al 2012b, Zollino et al 2012, Zollino et al 2015, Koolen et al 2016].
- Haploinsufficiency of KANSL1 due to chromosome rearrangements [Moreno-Igoa et al 2015].
Molecular genetic testing approaches can include a combination of chromosomal microarray (CMA), single-gene testing, a multigene panel, and comprehensive genomic testing (exome sequencing, exome array, genome sequencing).
Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including KANSL1) that cannot be detected by sequence analysis. CMA is recommended first because deletions are identified in ~95% of probands (see Table 1). The ability to determine the size of the deletion depends on the type of microarray used and the density of probes in the 17q21.31 region.
If chromosomal microarray does not identify the cause of the individual’s features, gene-targeted testing, which requires that the clinician to determine which gene(s) are likely involved, or genomic testing may be considered. Because the phenotype of KdVS is broad, individuals with the distinctive findings described in Suggestive Findings may be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of KdVS has not been considered are more likely to be diagnosed using other genomic testing (see Option 2).
Option 1
If a chromosome 17q21.31 deletion is not identified on CMA, testing options include the following:
- Single-gene testing. Sequence analysis of KANSL1 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 that may have been missed on CMA.
- An intellectual disability multigene panel that includes KANSL1 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 diagnosis of KdVS is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is the most commonly used genomic testing method; genome sequencing is also possible.
If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
Further Testing to Consider
If a 17q21.31 deletion is not identified on CMA and an intragenic pathogenic variant has not been identified on either a multigene panel or comprehensive genomic testing (genomic sequencing and exome array), additional options for testing include karyotype. A chromosome translocation with a 17q21.31 breakpoint that disrupted KANSL1 has been observed in one case report [Moreno-Igoa et al 2015].
Table 1.
Molecular Genetic Testing Used in Koolen-de Vries Syndrome
| Gene 1 | Method | Proportion of Probands with a Pathogenic Variant 2 Detectable by Method |
|---|---|---|
| KANSL1 | CMA 3, 4 | ~95% 5 |
| Sequence analysis 6 | ~5% | |
| Gene-targeted deletion/duplication analysis 7 | See footnote 8 | |
| Karyotype (to detect structural variants) | Rare 9 |
- 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.
The majority of affected individuals are identified by a genome-wide CMA screen for deletions/duplications that includes probe coverage of KANSL1. The ability to size the deletion depends on the type of microarray used and the density of probes in the 17q21.31 region. It is too early to ascertain the frequency of the 17q21.31 microdeletion and a KANSL1 pathogenic variant. Given the fact that the chromosome locus involved is flanked by segmental duplications, predisposing the locus to undergo deletion, it is likely that the recurrent microdeletion occurs more frequently.
- 4.
To date, testing in all unaffected parents from whom the deleted chromosome 17 originated has shown a 900-kb inversion involving chromosome 17q21.31. The frequency of this inversion (also referred to as the H2 lineage) in these parents is significantly greater than the ~20% frequency of the inversion found in the European population as a whole [Stefansson et al 2005] (p<10-5, Pearson's Chi square test) [Koolen et al 2008]. Testing for the inversion is not routinely indicated (see Molecular Genetics).
- 5.
CMA testing is appropriate to define breakpoints of large deletions; however, intragenic deletions in KANSL1 may not be detected by this method. Note: To date, all KANSL1 intragenic deletions reported have been identified through CMA analysis.
- 6.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. 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.
- 7.
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.
- 8.
Gene-targeted methods will detect single-exon up to whole-gene deletions; however, breakpoints of large deletions and/or deletion of adjacent genes may not be determined. KANSL1 gene-targeted deletion/duplication analysis could be considered if CMA and sequence analysis are not diagnostic, as smaller, atypical deletions encompassing part of KANSL1 have been reported [Cooper et al 2011, Dubourg et al 2011, Kitsiou-Tzeli et al 2012, Koolen et al 2012b].
- 9.
Moreno-Igoa et al [2015]
Clinical Characteristics
Clinical Description
Koolen-de Vries syndrome (KdVS) has a clinically recognizable phenotype that includes neonatal/childhood hypotonia, developmental delay / intellectual disability, dysmorphisms (Figure 1), speech and language delays, congenital malformations, and behavioral features (Table 2). Males and females are affected equally.
Table 2.
Features of Koolen-de Vries Syndrome
| Frequency | Feature |
|---|---|
| Very common (>75% of individuals) |
|
| Common (50%-75%) |
|
| Less common (25%-50%) |
|
| Occasional (10%-25%) |
|
| Infrequent (<10%) |
|
Clinical information based on data entered in the HDG website Series
Dysmorphic craniofacial features that may suggest KdVS:
- Upslanted palpebral fissure
- Blepharophimosis
- Epicanthus
- Ptosis
- Pear-shaped nose
- Bulbous nose
- Large/protruding ears
The nose can have a high nasal bridge, a broad nasal root, long columella, and underdeveloped and/or thick alae nasi. The facial characteristics change with age. In infancy the facial gestalt is mostly characterized by hypotonia with an open mouth appearance. With increasing age there is usually elongation of the face and broadening of the chin, and the "tubular'' or "pear'' shape form of the nose may become more apparent.
Hypotonia with poor sucking and slow feeding can be evident in the neonatal period and during childhood. Feeding difficulties may require hospitalization and/or nasogastric tube feeding in some neonates. Beyond infancy and into the preschool years, many children experience problems chewing difficult, lumpy, or solid textures [Morgan et al 2018a].
Psychomotor developmental delay is noted in all individuals from an early age. The level of developmental delay varies significantly. The majority of individuals with KdVS function in the mild-to-moderate range of intellectual disability.
- Communication disorder is a core feature of KdVS with a common speech and language phenotype seen. This includes an overriding "double hit" of oral hypotonia and apraxia in infancy and preschool, associated with severely delayed speech development [Morgan et al 2018a].
- First words occur between ages 2.5 and 3.5 years on average.
- Childhood apraxia of speech (CAS) is common in these preschool years, and speech development is effortful even when supported with intensive therapy.
- Augmentative (e.g., sign language) or alternative (e.g., communication devices) communication may alleviate frustration for the child and promote communication development.
- Overall, however, speech prognosis is positive, with CAS improving markedly around age eight to 12 years. At this time, the dysarthric element of speech is more apparent with a slow rate and monotone presentation.
- Stuttering is present in a handful of cases (17%), and has been noted in adolescence only.
- Receptive and expressive language abilities are typically commensurate (79%), both being severely affected relative to peers.
- Children are reported as sociable with a desire to communicate; in some individuals (36%) social skill impairments appear with increasing age and increasing social demands.
Epilepsy, including generalized seizures and unilateral clonic seizures, is noted in approximately 33% of affected individuals. The epilepsy phenotypic spectrum in KdVS is broad; however, most individuals have focal seizures, with some having a phenotype resembling the self-limited focal epilepsies of childhood [Myers et al 2017].
- The typical epilepsy phenotype of KdVS involves childhood-onset focal seizures that are prolonged and have prominent autonomic features.
- Multifocal epileptiform discharges are the typical EEG pattern.
- Structural brain abnormalities may be universal, including signs of abnormal neuroblast migration and abnormal axonal guidance (see Table 2).
Other common findings (see Table 2) include dental anomalies, slender long fingers, persistence of the fetal fingertip pads, hypoplasia of the hand muscles, slender lower limbs, joint hypermobility, hip dislocation, and positional deformities of the feet. In addition, multiple nevi, other pigmentary skin abnormalities, and hair abnormalities have been reported [Wright et al 2011, Zollino et al 2015, Koolen et al 2016].
- Congenital heart defects mainly include septal heart defects; however, cardiac valve disease, aortic root dilatation, and pulmonary stenosis have also been described.
- Renal and urologic anomalies include vesicoureteral reflux, hydronephrosis, pyelectasis, and duplex renal system. Cryptorchidism has been reported in the majority of males.
- Scoliosis is the most commonly observed spine anomaly; lordosis and kyphosis have also been reported and sometimes require surgery [Koolen et al 2008, Tan et al 2009].
- Behavior. In the vast majority of individuals, behavior is described as friendly, amiable, and cooperative, with or without frequent laughing. However, behavior problems, including attention-deficit/hyperactivity disorder, have been reported [Koolen et al 2008, Tan et al 2009, Koolen et al 2016].
Growth. Short stature is not one of the most common clinical features of the syndrome. However, El Chehadeh-Djebbar et al [2011] reported on a child with a 17q21.31 deletion, short stature (-4 SD), complete growth hormone deficiency, and gonadotropic deficiency [El Chehadeh-Djebbar et al 2011]. Brain MRI showed partial pituitary stalk interruption, expanding the phenotypic spectrum of the syndrome.
Life span. Longitudinal data are insufficient to determine life expectancy, although survival into adulthood is typical.
Genotype-Phenotype Correlations
Genotype-phenotype correlations in KdVS have not been shown. Notably, the clinical features of affected individuals with atypical deletions and those with pathogenic variants in KANSL1 are in keeping with the phenotype seen in individuals with a classic 17q21.31 deletion [Zollino et al 2015, Koolen et al 2016].
Penetrance
Penetrance is 100%: clinical features of KdVS are apparent in all individuals with a deletion of or a pathogenic variant in KANSL1, although the extent and severity of clinical findings vary among individuals.
Nomenclature
The disorder was first recognized following microarray analysis among large cohorts of unselected individuals with intellectual disability [Koolen et al 2006, Sharp et al 2006, Shaw-Smith et al 2006]. The identification of individuals with a similar phenotype and a de novo KANSL1 pathogenic variant [Koolen et al 2012b, Zollino et al 2012] led OMIM to assign the name "Koolen-de Vries syndrome" to the condition.
Prevalence
The prevalence of Koolen-de Vries syndrome is unknown. The authors estimate the prevalence of the 17q21.31 deletion at 1:55,000 individuals [Koolen et al 2016]. The prevalence of individuals with a pathogenic sequence variant in KANSL1 cannot be determined with precision owing to the limited number of such affected individuals identified thus far. Preliminary data suggest that pathogenic KANSL1 sequence variants may be as frequent as deletions, but more studies are needed to determine an unbiased prevalence.
Koolen-de Vries syndrome occurs with equal frequency in males and females [Koolen et al 2008].
Differential Diagnosis
The most common findings in Koolen-de Vries syndrome (KdVS), developmental delay and childhood hypotonia, are common and relatively nonspecific indications for molecular cytogenetic analysis. However, the concurrent finding of characteristic facial dysmorphic features, epilepsy, hypermetropia, congenital heart defects, renal or urologic anomalies, cryptorchidism, and/or friendly/amiable behavior may prompt specific consideration of the diagnosis of Koolen-de Vries syndrome. See Table 3 for other diagnoses with developmental delay and intellectual disability that may be considered in affected individuals.
Table 3.
Disorders with Developmental Delay and Intellectual Disability to Consider in the Differential Diagnosis of Koolen-de Vries Syndrome (KdVS)
| Disorder | Gene / Genetic Mechanism | MOI | Features of Differential Diagnosis Disorder | |
|---|---|---|---|---|
| Additional features overlapping w/KdVS | Distinguishing from KdVS | |||
| Deletion 22q11.2 1 (velocardiofacial syndrome) | 22q11.2 deletion | AD 2 |
|
|
| Prader-Willi syndrome | Abnormal parent-specific imprinting w/in Prader-Willi critical region | See footnote 3 |
|
|
| Fragile X syndrome | Genetic alteration in FMR1 | XL | Facial gestalt (adult males w/KdVS may show some coarsening & elongation w/↑ age) | Overactivity, impulsivity, & challenging behavior more common |
| Angelman syndrome | Disruption of maternally imprinted UBE3A | See footnote 4 |
|
|
| Cardiofaciocutaneous syndrome | BRAF 6 MAP2K1 MAP2K2 KRAS | AD 2 |
|
|
| WAC-related ID | WAC | AD 2 |
| Epilepsy less common |
| Say-Barber-Biesecker variant of Ohdo syndrome (see KAT6B-Related Disorders) | KAT6B | AD 2 |
|
|
AD = autosomal dominant; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked
- 1.
KdVS may be considered in individuals who tested negative for deletion of 22q11.2.
- 2.
Typically de novo
- 3.
The risk to sibs of a proband with PWS depends on the genetic mechanism that resulted in the absence of expression of the paternally contributed 15q11.2-q13 region.
- 4.
The risk to sibs of a proband with Angelman syndrome depends on the genetic mechanism leading to the loss of UBE3A function.
- 5.
Research shows that prognosis for speech in individuals with KdVS is positive; apraxia resolves, and although dysarthria persists, most children are intelligible by mid-to-late childhood [Morgan et al 2018a]. Speech delay in children with Angelman syndrome remains far more severe [Grieco et al 2018], however, there is little published information on communication in individuals with Angelman syndrome.
- 6.
75% of individuals with cardiofaciocutaneous syndrome have a pathogenic variant in BRAF. Three other genes known to be associated with CFC syndrome are: MAP2K1 and MAP2K2 (~25%), and KRAS (<2%).
Management
Evaluations Following Initial Diagnosis
To establish the clinical consequences in an individual diagnosed with Koolen-de Vries syndrome (KdVS), the following evaluations are recommended if they have not already been completed.
Table 4.
Recommended Evaluations Following Initial Diagnosis of Koolen-de Vries Syndrome
System/Concern | Evaluation | Comment |
|---|---|---|
| Constitutional | Assessment of growth parameters to identify those w/failure to thrive | Consider investigation of growth hormone deficiency in individuals w/short stature. |
| Eyes | Ophthalmology evaluation | |
| ENT/Mouth | Audiologic examination | |
| Cardiovascular | Cardiac evaluation | For possible heart anomalies incl septal defects & aortic dilatation |
| Gastrointestinal/ Feeding | Feeding assessment | Asses for sucking & swallowing difficulties & need for feeding therapy in infancy. |
| Genitourinary |
| Evaluate for ureteral reflux & other renal problems. |
| Neurologic | Developmental assessment | To incl motor, speech/language evaluation, general cognitive, & vocational skills |
| Neuropsychiatric evaluation | Screen for behavior concerns incl sleep disturbances, ADHD, anxiety, &/or traits suggestive of ASD. | |
| Brain imaging studies in individuals w/microcephaly &/or seizure | Consideration of a Chiari malformation type 1 in those w/suggestive symptoms (headache, neck pain, cerebellar signs, or muscle weakness) 1 | |
| EEG if seizures are suspected | Referral to neurologist for seizure disorder management | |
| Miscellaneous/ Other | Consultation w/clinical geneticist &/or genetic counselor |
ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder
- 1.
Terrone et al [2012]
Treatment of Manifestations
Treatment includes routine medical care by a pediatrician or other primary physician and the following.
Table 5.
Treatment of Manifestations in Individuals with Koolen-de Vries Syndrome
| Manifestation/ Concern | Treatment | Considerations/Other |
|---|---|---|
| Feeding problems & motor delay related to hypotonia | Early intervention / feeding therapy / physiotherapy | Nasogastric tube feeding may be required for neonates w/severe feeding issues. |
| Vision issues / strabismus | Standard management for visual problems as directed by ophthalmologist | |
| Hearing loss | Standard management | |
| Cardiac, renal, urologic, & other medical issues | Standard management of specific issue | |
| Cryptorchidism | Treatment by urologist, if indicated | |
| Seizures | Standard treatment / routine antiepileptic drugs under care of neurologist | |
| Speech & language |
| |
| Scoliosis / Hip dislocation / Positional deformities of the feet | Standard orthopedic care | |
| Multiple nevi | Regular checkup by dermatologist if multiple nevi present |
The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States (US); standard recommendations may vary from country to country.
Developmental Disability / Intellectual Disability Management Issues
Children with KdVS require early, intensive speech motor and language therapy, with targeted literacy and social language interventions as developmentally appropriate.
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 and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).
- Consider use of durable medical equipment as needed (e.g., 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]) used alongside verbal therapies for individuals who have expressive language difficulties. Intensive verbal speech therapy approaches for childhood apraxia of speech are recommended in the early years [Morgan et al 2018b] and literacy, dysarthria, and social skill therapies are required in the school years.
Social/Behavioral Concerns
Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including 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 when necessary.
Surveillance
Table 6.
Recommended Surveillance for Individuals with Koolen-de Vries Syndrome
| System/Concern | Evaluation | Frequency |
|---|---|---|
| Constitutional | Ongoing pediatric care | |
| Eyes | Ophthalmology evaluation due to ↑ risk for hypermetropia & strabismus | Routine intervals |
| Cardiovascular | Monitoring as needed | |
| Genitourinary | Monitoring as needed | |
| Musculoskeletal | Monitoring for spine deformities/scoliosis | Routine intervals until growth is complete |
| Neurologic | Specialized neurologic care for individuals w/epilepsy | |
| Miscellanous/ Other | Monitor developmental progress & educational needs |
Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
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.