Clinical characteristics.

Classically, Coffin-Siris syndrome (CSS) was characterized by specific dysmorphic features (coarse facies, sparse scalp hair, thick eyebrows with long lashes, wide nasal bridge with broad nasal tip, anteverted nares with thick ala nasi, wide mouth with thick, everted vermilion of the upper and lower lips, and hypertrichosis), the absence or underdevelopment of the fifth digit finger/toe or nail, learning and developmental differences, and various organ system-related anomalies. As genetic technology has evolved, more individuals with subtle physical exam findings are being diagnosed with CSS. The vast majority of affected individuals have developmental delay / intellectual disability, typically in the moderate-to-severe range, although those with mild cognitive impairment or even normal intelligence have more rarely been described. Most affected individuals have feeding difficulties (with ~25%-50% requiring a feeding tube in childhood, some of whom then outgrow it), hypotonia, and frequent infections. About half of affected individuals have epilepsy. Other findings may include skeletal features (joint laxity, scoliosis), hearing impairment (both conductive and sensorineural), eye issues (ptosis, strabismus), congenital heart defects, genitourinary malformations, and behavioral issues (including hyperactivity and/or aggressiveness).

Diagnosis/testing.

The diagnosis of CSS is established in a proband with suggestive findings and a heterozygous pathogenic variant in one of the following 14 known genes identified by molecular genetic testing: ARID1A, ARID1B, ARID2, BICRA, DPF2, PHF6, SMARCA2, CMARCA4, SMARCB1, SMARCC2, SMARCD1, SMARCE1, SOX4, or SOX11.

Management.

Treatment of manifestations: Feeding therapy with consideration of placement of gastrostomy tube in those with persistent feeding issues. Standard treatment for developmental delay / intellectual disability, epilepsy, tics, sleep disturbance, scoliosis, joint laxity, knee subluxations, obesity, refractive error, strabismus, ptosis, hearing loss, congenital heart defects, undervirilization, inguinal hernia, frequent infections, and hepatoblastoma.

Surveillance: At each visit, measurement of growth parameters; evaluation of nutrition status and safety of oral intake; assessment for new neurologic manifestations, such as seizures or tics; monitoring of developmental progress and educational needs; behavioral assessment for anxiety, ADHD, ASD, aggression, & self-injury; monitoring for signs and symptoms of sleep disturbance; evaluation for mobility and self-help skills; and assessment for signs and symptoms of frequent infections. Annually or as clinically indicated, ophthalmology evaluation and vision assessment; audiology evaluation. At least every six months in those with teeth, dental evaluation. In those with ARID1A-related CSS: serum AFP level (with consideration of liver ultrasound) every three months until age four years.

Genetic counseling.

CSS is inherited in an autosomal dominant manner; however, most affected individuals have the disorder as the result of a de novo CSS-causing pathogenic variant. If the CSS-causing pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Suggestive Findings

CSS should be suspected in individuals with the following clinical findings and family history:

Clinical findings

• Facial features (see Figure 1A, 1B, 1C) including:
  • Coarse facies
  • Sparse scalp hair, particularly in the temporal regions, especially in infancy
  • Thick eyebrows
  • Long eyelashes
  • Wide nasal bridge with broad nasal tip
  • Anteverted nares with thick ala nasi
  • A wide mouth with thick, everted vermilion of the upper and lower lips suggestive of coarseness
• Fifth digit nail / distal phalanx hypoplasia/aplasia (Figure 1D, 1E, 1F, 1G)
• Hirsutism/hypertrichosis. Hair growth in atypical areas (e.g., the back) or excessive hair growth on the arms or face
• Central hypotonia
• Developmental delay (DD) or intellectual disability (ID) of variable degree, most typically in the moderate-to-severe range

Figure 1.

Coffin-Siris syndrome classic features Facial features in a one-year-old girl (A), a young adult female (B), and a young adult male (C). Coarse facial features are evident in A but tend to become more apparent as individuals age; these may include thick (more...)

Family history. Because CSS is typically caused by a de novo pathogenic variant, most probands represent a simplex case (i.e., a single occurrence in a family). Rarely, the family history may be consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations).

Establishing the Diagnosis

The diagnosis of CSS is established in a proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in one of the genes listed in Table 1 identified by molecular genetic testing.

Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this GeneReview is understood to include likely pathogenic variants. (2) Identification of a heterozygous variant of uncertain significance (VUS) in one of the genes listed in Table 1 does not establish or rule out the diagnosis.

Molecular genetic testing approaches can include a combination of gene-targeted testing (single gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see Option 1), whereas comprehensive genomic testing does not (see Option 2).

Clinical Description

The clinical manifestations of Coffin-Siris syndrome have expanded over the years as greater phenotypic variability has been recognized. Classically, the syndrome was first identified by the absence or underdevelopment of the fifth digit finger/toe or nail. Additional "classic" features have included sparse scalp hair, hypertrichosis, learning and developmental differences, and various organ system-related anomalies. As genetic technology has evolved, more individuals with subtle physical exam findings are being diagnosed with CSS.

To date, at least 550 individuals have been identified with a diagnosis of Coffin-Siris syndrome, including those enrolled in the Coffin-Siris syndrome / BAF complex registry [Wieczorek et al 2013; Kosho et al 2014; Santen et al 2014; Ciliberto et al 2023; Schmetz et al 2024; Schrier Vergano 2024; S Schrier Vergano, unpublished data]. ARID1B has been reported in around 1% of cohorts of individuals with neurodevelopmental disorder [Hoyer et al 2012]. The following description of the phenotypic features associated with this condition is based on these reports.

Dysmorphic facial features typically prompt consideration of this diagnosis (see Suggestive Findings and Figures 1A, 1B, 1C).

Developmental delay (DD) and intellectual disability (ID). Intellectual disability is present in most and is typically moderate to severe (IQ range: 40 to 69); however, IQ as high as 97 has been reported [Santen et al 2012]. Ranges of IQ/DQ (developmental quotient) may depend on the gene involved and the degree of other medical challenges (see Phenotype Correlations by Gene).

While formal studies of IQ have not yet been conducted, those who have been tested range from mild to severe depending on the gene (i.e., individuals with ARID2-related CSS tend to range from mild to moderate) [Schrier Vergano 2024].

• On average, children with CSS learn to sit at 12 months, walk at 30 months, and speak their first words at 24 months.
• Expressive language is more severely affected than receptive language, with no speech in about 12% of individuals (median age: 10 years). A review of language acquisition in registry-enrolled individuals reported by Vasko & Schrier Vergano [2022] identified that:
  • 26% of individuals had normal speech development (words by 18 months)
  • <1% had mild development delay (speech by 19-21 months)
  • 13% had moderate speech delay (speech by 22-25 months)
  • 60% had severe speech delay (speech after 25 months)
• In a study of 35 adult individuals with CSS, only one presented with absence of ID [Schmetz et al 2024].

Other neurodevelopmental features

• Hypotonia is usually noted in infancy and is typically persistent, although some affected individuals experience improvement with age and therapies.
• Infant feeding difficulties may be due to an oral aversion or difficulty feeding in the absence of any evident intestinal malformations. Approximately 25%-50% of reported individuals used a feeding tube, some of whom grew out of it [Mannino et al 2018] (see Management).

Epilepsy/tics. Both seizures and tics have been described in affected individuals. Seizure frequency may be as high as 38% but has varied depending on the age of the cohort [Ciliberto et al 2023]. A variety of seizure types have been reported. There is no typical age of onset for seizures or tics. Seizures can begin even in the teenage years, and some affected individuals may begin experiencing seizures after puberty. The majority of affected individuals who develop seizures appear to respond to traditional anti-seizure medication [Ciliberto et al 2023] (see Management).

Neurobehavioral/psychiatric manifestations. Autism has been reported in as high as 44% of individuals, although as with many features, the true prevalence may be underestimated depending on the age of the individual and available testing/evaluations [Vasko & Schrier Vergano 2022]. Behavioral abnormalities include hyperactivity (~10%), aggressiveness (~10%), and attention-deficit/hyperactivity disorder (25%).

Sleep disturbances are not uncommon but the prevalence of certain conditions like narcolepsy and restless leg syndrome are unknown. Many families report disrupted sleep, particularly in individuals with a concomitant diagnosis of autism.

Skeletal findings. The most striking clinical feature of CCS is the finding of small nails on the fifth finger or toe, affecting about 40% of individuals. Individuals with a diagnosis of CSS have either aplasia or hypoplasia of the distal phalanx or absence of the nail, typically involving the fifth finger, but other digits may also be affected. Toes can also be affected, where the finding tends to involve multiple digits. As the phenotype expands, more individuals with pathogenic variants in the BAF complex do not have the classic digit findings (see Molecular Pathogenesis).

Other skeletal findings can include the following:

• Joint laxity (66%). Some individuals may have an increased prevalence of knee subluxations [van der Sluijs et al 2024].
• Scoliosis (30%-40%). This appears to be primarily neuromuscular in origin. If present, it should continue to be monitored by primary providers with a referral to an orthopedist if it is rapidly progressive or impacting respiratory efforts (see Management).
• Delayed bone age (40%)
• Fifth digit clinodactyly of the hands

Skin and hair findings

• Hypertrichosis (95%) may appear in areas unexpected for an individual's ancestry (i.e., back, shoulders).
• A low anterior hairline is common (75%).
• Sparse scalp hair (60%), particularly involving the temporal region. Hair may appear at an appropriate age but may be very thin.
• Hernias (10%)

Growth issues/dental. Weight and height is below the 50th centile for most, and below the 5th centile for 20%-35% of affected individuals. Nineteen of 35 adult individuals with CSS were reported to have obesity [Schmetz et al 2024].

• Bone age typically lags about two to three years behind chronologic age.
• Primary and secondary dentition is delayed in about 40% of affected individuals.

Hearing impairment (15%-45%) is often associated with recurrent upper respiratory tract infections. Both sensorineural and conductive hearing loss has been reported, although conductive hearing loss occurs more often due to frequent infections or small ear canals. A minority of individuals with hearing loss need hearing aids (see Management).

Ophthalmologic abnormalities can include ptosis (50%), strabismus (50%), and/or myopia (20%). In a cohort of 35 adults, 29 had ophthalmic issues [Schmetz et al 2024].

Frequent infections. These are poorly characterized but are often consistent with upper respiratory viral infections. While some individuals with CSS have undergone immunology testing, there do not appear to be consistent defects in cellular immunity. Much of the frequency of illnesses may be attributed to overall hypotonia and difficult with clearing of secretions.

Other associated features

• Cardiac anomalies have been reported in about one third of affected individuals and have included ventricular septal defects, atrial septal defects, tetralogy of Fallot, and patent ductus arteriosus.
• Renal and genitourinary malformations can include cryptorchidism (in males) most commonly, but also horseshoe kidney, hypospadias, and other abnormalities.
• Neuroimaging. Central nervous system malformations can include Dandy-Walker variant, gyral simplification, and agenesis of the corpus callosum.

Tumor risk. Although pathogenic variants in a subset of the genes causing CSS have been implicated in tumorigenesis, data on tumor risk in CSS are lacking. Tumors have been reported in individuals with CSS, but not all cases are connected to the constitutional CSS genetic change. In a cohort of 35 adults with CSS, no one had a malignancy [Schmetz et al 2024]. Apart from hepatoblastoma screening, routine cancer surveillance is not recommended.

• Pathogenic variants in ARID1A have been associated with a number of cases of hepatoblastoma, and the frequency is estimated to be about 3.6% [Tsurusaki et al 2012, Kosho et al 2014, Cárcamo et al 2022, Borja et al 2023, van der Sluijs et al 2023]. As this frequency appears to exceed the recommended 1% screening threshold for hepatoblastoma in the United States, consideration of alpha-fetoprotein levels (AFPs) every three months may be warranted (see Management).
• An individual with a 4.2-Mb deletion that included (among 14 genes) ARID1B developed papillary thyroid cancer [Vengoechea et al 2014]. However, given the large number of individuals reported with ARID1B pathogenic variants with no subsequent reports of thyroid cancer, the authors feel that it is unlikely that there is a strong relationship between the two.
• Multiple studies have reported the same single individual who has CSS, schwannomatosis, and a pathogenic variant in SMARCB1 [Carter et al 2012, Schrier et al 2012, Gossai et al 2015]. Formal screening recommendations have not been developed at this time, but clinicians should be aware of the possibility of schwannomas in individuals with a pathogenic variant in SMARCB1.

Prognosis. In the absence of long-term studies, information on life span in individuals with CSS is not available. Children have been reported to succumb to aspiration pneumonia and/or seizures, although this is not common [Schrier et al 2012]. As with any rare conditions, individuals with tracheostomies or needing respiratory support may have higher mortality at younger ages.

It is unknown whether life span in CSS is abnormal. One reported individual is alive at age 69 years [Määttänen et al 2018], demonstrating that survival into adulthood is possible. Schmetz et al [2024] reported 35 individuals aged 18 to 37 years, and van der Sluijs et al [2024] reported a large cohort of adults with CSS aged 18-69 years. Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported.

Phenotype Correlations by Gene

Phenotype correlations by gene have been seen in individuals with pathogenic variants in ARID1A, ARID1B, ARID2, BICRA, DPF2, SMARCA4, SMARCB1, SMARCE1, SOX4, and SOX11 [Wieczorek et al 2013, Kosho et al 2014, Santen et al 2014, Tsurusaki et al 2014a, Hempel et al 2016, Vasileiou et al 2018, Gazdagh et al 2019, Machol et al 2019, Zawerton et al 2019, Bosch et al 2023, Schmetz et al 2024].

ARID1A. Heterozygous pathogenic variants in ARID1A have been associated with a number of cases of hepatoblastoma; the risk is estimated to be about 3.6% (see Clinical Description, Tumor risk).

ARID1B. Individuals with a pathogenic variant in ARID1B are typically at the milder end of the spectrum of CSS and often have normal growth. Moderately severe feeding problems are noted in two thirds, seizures in one third, and hypoplasia of the corpus callosum in one third of affected individuals. Facial gestalt is consistent with CSS, albeit at times milder.

ARID2. Affected individuals typically do not have significant birth defects but may have short stature, mild-to-moderate learning and developmental differences, and hypotonia. Hip dysplasia appears more common in individuals with ARID2-related CCS than in those with CSS due to other genes [Schrier Vergano 2024].

BICRA. A small cohort of individuals with a pathogenic variant in BICRA have been reported; individuals appear to have moderate-to-severe developmental delay / intellectual disability with autism, seizures, and behavioral challenges. However, one affected individual with a heterozygous pathogenic variant in BICRA has been reported with normal intelligence. Classic CSS features, such as digital anomalies, have not been consistently reported.

DPF2. Individuals with a pathogenic variant in DPF2 tend to have mild-to-moderate learning and developmental differences, as well as some classic CSS features including digital anomalies and coarse facial features.

SMARCA4. Individuals with a pathogenic variant in SMARCA4 appear to have growth impairment that is mild prenatally and mild to moderate postnatally; sucking/feeding difficulty is almost always observed. While individuals can sometimes have severe developmental delays, significant behavioral challenges tend to be more characteristic. Facial features have demonstrated less coarseness, while hypoplastic fifth fingers or toes and hypoplastic fifth fingernails or toenails are a near-constant finding (with hypoplasia of other fingernails or toenails being an occasional finding). Prominence of interphalangeal joints and distal phalanges is also noted in some affected individuals.

SMARCB1. Individuals with a pathogenic variant in SMARCB1 typically are more severely affected; all have growth impairment (usually noted as mild prenatally and moderate to severe postnatally) with sucking/feeding difficulties. Structural central nervous system abnormalities with hypotonia and seizures are typical findings, accompanied by severe developmental delay / intellectual disability. Affected individuals are usually nonverbal. Typical skeletal findings include hypoplastic fifth fingers or toes, hypoplastic other fingernails or toenails, prominent distal phalanges, and scoliosis. Some individuals may walk independently. Gastrointestinal complications and hernia as well as cardiovascular and genitourinary complications are common.

SMARCE1. Individuals with pathogenic SMARCE1 variants tend to have severe intellectual disability, typical facial gestalt, and hypoplastic or absent fifth finger- and toenails associated with hypoplasia of other nails. The hands are characterized by long and slender fingers. Individuals are typically small for gestational age and have postnatal short stature and severe microcephaly, complex congenital heart defects, feeding difficulties, and seizures.

SOX4. Severely affected individuals may show neurologic complications including hypotonia, spastic quadriparesis, and epilepsy.

SOX11. Neurodevelopmental abnormalities tend to be more prevalent than organ system or physical complications, but cohort studies have identified idiopathic hypogonadotropic hypogonadism and physical features including microcephaly and short stature, with some researchers suggesting that it may represent a separate neurodevelopmental condition [Al-Jawahiri et al 2022].

Genotype-Phenotype Correlations

No clinically relevant genotype-phenotype correlations have been identified for ARID1A, ARID2, BICRA, DPF2, PHF6, SMARCA2, SMARCA4, SMARCB1, SMARCC2, SMARCD1, SMARCE1, SOX4, or SOX11.

ARID1B. Affected individuals with a pathogenic variant in exon 1 of ARID1B may have a milder phenotype. Although some individuals with this type of pathogenic variant have features that are indistinguishable from those with pathogenic variants in the other exons of ARID1B, other individuals with pathogenic variants in exon 1 have very mild clinical features. Inheritance from apparently unaffected parents has been occasionally described in individuals who have a pathogenic variant in exon 1, although usually parents who have undergone more thorough phenotyping may be found to also be mildly affected. This has not been described up to now for pathogenic variants in the other exons (see ARID1B-Related Disorder).

Prevalence

More than 530 individuals with molecularly confirmed CSS have been reported (per the CSS registry). Rough estimates suggest a possible frequency of one in 100,000 births based on known cases, indicating that the diagnosis is still rare. True prevalence is likely higher.

In addition, the identification of a pathogenic variant in ARID1B in some members of a large cohort with intellectual disability [Hoyer et al 2012] suggests that the prevalence of pathogenic variants in genes associated with CSS (and possibly of subtle phenotypic features of CSS) may be higher than currently appreciated among those with apparently nonsyndromic intellectual disability.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with CSS, the evaluations summarized in Table 5 (if not performed as part of the evaluation that led to diagnosis) are recommended.

Treatment of Manifestations

There is no cure for CSS. Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see Table 6).

Surveillance

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in Table 7 are recommended.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Van der Sluijs et al [2025] examined the utility of clonazepam in individuals with CSS based on preliminary data that identified decreased GABA-ergic inhibitory synapses in Arid1b⁺ mice, with some possible improvement in tone and attention to tasks and decreased anxiety [Jung et al 2017]. This study concluded that clonazepam did not provide any additional benefit to individuals with CCS due to pathogenic variants in ARID1B [van der Sluijs et al 2025].

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.

Mode of Inheritance

Coffin-Siris syndrome (CSS) is an autosomal dominant disorder typically caused by a de novo pathogenic variant.

Risk to Family Members

Parents of a proband

• Most individuals diagnosed with CSShave the disorder as the result of a de novo CSS-causing pathogenic variant.
• Rarely, an individual diagnosed with CSS has an affected parent.
  • Transmission of a SOX11 pathogenic variant from a mother with mild learning differences to two daughters with intellectual disability has been reported [Hanker et al 2022]. All three individuals had hypoplastic nails and similar facial features. Additional individuals with maternally inherited SOX11 pathogenic variants and variable degrees of intellectual disability have been observed [S Schrier Vergano, unpublished data].
  • Several inherited ARID1B pathogenic variants in exon 1 have been described, often inherited from a mildly affected parent [van der Sluijs et al 2021].
• If a molecular diagnosis has been established in the proband and the proband appears to be the only affected family member (i.e., a simplex case), molecular genetic testing is recommended for the parents of the proband to evaluate their genetic status and inform recurrence risk assessment.
• If the pathogenic variant identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:
  • The proband has a de novo pathogenic variant.
  • The proband inherited a pathogenic variant from a parent with gonadal (or somatic and gonadal) mosaicism [Ben-Salem et al 2016; Cheng et al 2021; S Schrier Vergano, personal observation/registry].* Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a pathogenic variant that is present in the germ (gonadal) cells only.
    * A parent with somatic and gonadal mosaicism for a CSS-causing pathogenic variant may be mildly/minimally affected [Cheng et al 2021].
• Evaluation of parents may determine that one is affected but has escaped previous diagnosis because of a milder phenotype. Therefore, an apparently negative family history cannot be confirmed without appropriate clinical evaluation of the parents and/or molecular genetic testing (if a molecular diagnosis has been established in the proband).

Sibs of a proband. The risk to the sibs of the proband depends on the clinical/genetic status of the proband’s parents:

• In the rare circumstance that a parent of the proband is affected and/or is known to have a CSS-causing pathogenic variant, the risk to the sibs is 50%.
• If the proband has a known CSS-causing pathogenic variant that cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental gonadal mosaicism [Ben-Salem et al 2016; Cheng et al 2021; S Schrier Vergano, personal observation/registry].
• If the parents are clinically unaffected but their genetic status is unknown, the risk to the sibs of a proband appears to be low but increased over that of the general population because of the possibility of parental gonadal mosaicism.

Offspring of a proband. Each child of an individual with CSS has a 50% chance of inheriting the CSS-related pathogenic variant.

Other family members. The risk to other family members depends on the status of the proband's parents: in the rare event of an affected parent, other family members may be at risk.

Related Genetic Counseling Issues

Family planning

• The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
• It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to couples who have had an affected child.

DNA banking. Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see Huang et al [2022].

Prenatal Testing and Preimplantation Genetic Testing

Once the Coffin-Siris syndrome-causing pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal t and preimplantation genetic esting. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.

Molecular Pathogenesis

Many of the genes identified to be causative of the Coffin-Siris syndrome (CSS) phenotype to date encode human homologs of proteins first identified in yeast and Drosophila in the BRG1- and BRM-associated factor (BAF) complex, originally called the mammalian switch/sucrose non-fermentable (mSWI/SNF)-like nucleosome remodeling complex. This complex contains a DNA-stimulated ATPase activity capable of destabilizing histone-DNA interactions in an ATP-dependent manner [Ronan et al 2013]. Transcription factor SOX-11 (SOX11; encoded by SOX11) is predicted to act downstream of the BAF complex in neurogenesis and may be involved in the conversion of postnatal glia into neurons [Ninkovic et al 2013].

Author Notes

All of the authors of this chapter study the clinical features and molecular basis of Coffin-Siris syndrome (CSS).

Dr Samantha Schrier Vergano at Seattle Children's Hospital is actively involved in clinical research regarding individuals with CSS and runs the CSS clinical registry. She would be happy to communicate with persons who have any questions regarding the diagnosis of CSS or other considerations. Email gro.snerdlihcelttaes@yrtsigerssc for more information.

Dr Dagmar Wieczorek at the Institute of Human Genetics has long-standing experience in the identification of new genes and signaling pathways related to neurodevelopmental disorders (NDD), autism, and syndromal entities (especially craniofacial malformations). She has more than ten years' experience in the use of next-generation sequencing for the detection of causative genetic variations. She hosts large patient cohorts for the study of NDD. In 2025, she will start as one PI in a natural history study on ARID1B-related disorders (www.care4arid1b.org).

Acknowledgments

Dr Schrier Vergano would like to acknowledge Ashley Vasko, BS, and Catherine Nguyen, MS, who assisted with the 2021 revision of this chapter.

Author History

Matthew A Deardorff, MD, PhD; University of Southern California (2013-2025)
Naomichi Matsumoto, MD, PhD (2013-present)
Gijs Santen, MD, PhD (2013-present)
Samantha Schrier Vergano, MD (2013-present)
Dagmar Wieczorek, MD (2013-present)
Bernd Wollnik, MD; University of Cologne (2013-2025)

Revision History

• 15 May 2025 (ma) Comprehensive update posted live
• 12 May 2016 (ha) Comprehensive update posted live
• 4 April 2013 (me) Review posted live
• 19 July 2012 (md) Original submission

Literature Cited

• Al-Jawahiri R, Foroutan A, Kerkhof J, McConkey H, Levy M, Haghshenas S, Rooney K, Turner J, Shears D, Holder M, Lefroy H, Castle B, Reis LM, Semina EV; University of Washington Centre for Mendelian Genomics (UW-CMG); Lachlan K, Chandler K, Wright T, Clayton-Smith J, Hug FP, Pitteloud N, Bartoloni L, Hoffjan S, Park SM, Thankamony A, Lees M, Wakeling E, Naik S, Hanker B, Girisha KM, Agolini E, Giuseppe Z, Alban Z, Tessarech M, Keren B, Afenjar A, Zweier C, Reis A, Smol T, Tsurusaki Y, Nobuhiko O, Sekiguchi F, Tsuchida N, Matsumoto N, Kou I, Yonezawa Y, Ikegawa S, Callewaert B, Freeth M; Genomics England Research Consortium; Kleinendorst L, Donaldson A, Alders M, De Paepe A, Sadikovic B, McNeill A. SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile. Genet Med. 2022;24:1261-73. [PMC free article: PMC9245088] [PubMed: 35341651]
• Asadauskaitė G, Morkuniene A, Utkus A, Burnyte B. Identification of a novel BICRA variant leading to the newly described Coffin-Siris syndrome 12. Brain Dev. 2023;45:185-90. [PubMed: 36437209]
• Barish S, Barakat TS, Michel BC, Mashtalir N, Phillips JB, Valencia AM, Ugur B, Wegner J, Scott TM, Bostwick B, Murdock DR, Dai H, Perenthaler E, Nikoncuk A, van Slegtenhorst M, Brooks AS, Keren B, Nava C, Mignot C, Douglas J, Rodan L, Nowak C, Ellard S, Stals K, Lynch SA, Faoucher M, Lesca G, Edery P, Engleman KL, Zhou D, Thiffault I, Herriges J, Gass J, Louie RJ, Stolerman E, Washington C, Vetrini F, Otsubo A, Pratt VM, Conboy E, Treat K, Shannon N, Camacho J, Wakeling E, Yuan B, Chen CA, Rosenfeld JA, Westerfield M, Wangler M, Yamamoto S, Kadoch C, Scott DA, Bellen HJ, et al. BICRA, a SWI/SNF complex member, is associated with BAF disorder-related phenotypes in humans and model organisms. Am J Hum Genet. 2020;107:1096–112. [PMC free article: PMC7820627] [PubMed: 33232675]
• Ben-Salem S, Sobreira N, Akawi NA, Al-Shamsi AM, John A, Pramathan T, Valle D, Ali BR, Al-Gazali L. Gonadal mosaicism in ARID1B gene causes intellectual disability and dysmorphic features in three siblings. Am J Med Genet A. 2016;170A:156–61. [PMC free article: PMC5448135] [PubMed: 26395437]
• Biegel JA, Busse TM, Weissman BE. SWI/SNF chromatin remodeling complexes and cancer. Am J Med Genet C Semin Med Genet. 2014;166C:350–66. [PMC free article: PMC4516040] [PubMed: 25169151]
• Borja NA, Schrier Vergano SA, Tekin M. Coffin-Siris syndrome and cancer susceptibility. Genet Med Open. 2023;1:100818. [PMC free article: PMC11613554] [PubMed: 39669229]
• Bosch E, Popp B, Güse E, Skinner C, van der Sluijs PJ, Maystadt I, Pinto AM, Renieri A, Bruno LP, Granata S, Marcelis C, Baysal Ö, Hartwich D, Holthöfer L, Isidor B, Cogne B, Wieczorek D, Capra V, Scala M, De Marco P, Ognibene M, Jamra RA, Platzer K, Carter LB, Kuismin O, van Haeringen A, Maroofian R, Valenzuela I, Cuscó I, Martinez-Agosto JA, Rabani AM, Mefford HC, Pereira EM, Close C, Anyane-Yeboa K, Wagner M, Hannibal MC, Zacher P, Thiffault I, Beunders G, Umair M, Bhola PT, McGinnis E, Millichap J, van de Kamp JM, Prijoles EJ, Dobson A, Shillington A, Graham BH, Garcia EJ, Galindo MK, Ropers FG, Nibbeling EAR, Hubbard G, Karimov C, Goj G, Bend R, Rath J, Morrow MM, Millan F, Salpietro V, Torella A, Nigro V, Kurki M, Stevenson RE, Santen GWE, Zweier M, Campeau PM, Severino M, Reis A, Accogli A, Vasileiou G. Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals. Genet Med. 2023;25:100950. [PubMed: 37551667]
• Cárcamo B, Masotto B, Baquero-Vaquer A, Ceballos-Saenz D, Zapata-Aldana E. Cancer in ARID1A-Coffin-Siris syndrome: review and report of a child with hepatoblastoma. Eur J Med Genet. 2022;65:104600. [PubMed: 36049608]
• Carter JM, O'hara C, Dundas G, Gilchrist D, Collins MS, Eaton K, Judkins AR, Biegel JA, Folpe AL. Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with "neuroblastoma-like" schwannomatosis and a novel germline SMARCB1 mutation. Am J Surg Pathol. 2012;36:154–60. [PMC free article: PMC3241826] [PubMed: 22082606]
• Cheng SSW, Luk HM, Mok MT, Leung SS, Lo IFM. Genotype and phenotype in 18 Chinese patients with Coffin-Siris syndrome. Am J Med Genet A. 2021;185:2250-61. [PubMed: 33768696]
• Ciliberto M, Skjei K, Vasko A, Schrier Vergano S. Epilepsy in Coffin-Siris syndrome: a report from the international CSS registry and review of the literature. Am J Med Genet A. 2023;191:22-28. [PubMed: 36177969]
• Gazdagh G, Blyth M, Scurr I, Turnpenny P, Mehta S, Armstrong R, McEntagart M, Newbury-Ecob R, Tobias E, Joss S, et al. Extending the clinical and genetic spectrum of ARID2 related intellectual disability. A case series of 7 patients. Eur J Med Genet. 2019;62:27–34. [PubMed: 29698805]
• Gossai N, Biegel JA, Messiaen L, Berry SA, Moertel CL. Report of a patient with a constitutional missense mutation in SMARCB1, Coffin-Siris phenotype, and schwannomatosis. Am J Med Genet A. 2015;167A:3186–91. [PubMed: 26364901]
• Halgren C, Kjaergaard S, Bak M, Hansen C, El-Schich Z, Anderson CM, Henriksen KF, Hjalgrim H, Kirchhoff M, Bijlsma EK, Nielsen M, Den Hollander NS, Ruivenkamp CA, Isidor B, Le Caignec C, Zannolli R, Mucciolo M, Renieri A, Mari F, Anderlid BM, Andrieux J, Dieux A, Tommerup N, Bache I. Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Clin Genet. 2012;82:248–55. [PMC free article: PMC3464360] [PubMed: 21801163]
• Hanker B, Gillessen-Kaesbach G, Hüning I, Lüdecke HJ, Wieczorek D. Maternal transmission of a mild Coffin-Siris syndrome phenotype caused by a SOX11 missense variant. Eur J Hum Genet. 2022;30:126-32. [PMC free article: PMC8738766] [PubMed: 33785884]
• Hasselblatt M, Gesk S, Oyen F, Rossi S, Viscardi E, Giangaspero F, Giannini C, Judkins AR, Fruhwald MC, Obser T, Schneppenheim R, Siebert R, Paulus W. Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression. Am J Surg Pathol. 2011;35:933–5. [PubMed: 21566516]
• Hempel A, Pagnamenta AT, Blyth M, Mansour S, Mcconnell V, Kou I, Ikegawa S, Tsurusaki Y, Matsumoto N, Lo-Castro A, Plessis G, Albrecht B, Battaglia A, Taylor JC, Howard MF, Keays D, Sohal AS, Kuhl SJ, Kini U, Mcneill A, et al. Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome. J Med Genet. 2016;53:152–62. [PMC free article: PMC4789813] [PubMed: 26543203]
• Hoyer J, Ekici AB, Endele S, Popp B, Zweier C, Wiesener A, Wohlleber E, Dufke A, Rossier E, Petsch C, Zweier M, Gohring I, Zink AM, Rappold G, Schrock E, Wieczorek D, Riess O, Engels H, Rauch A, Reis A. Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability. Am J Hum Genet. 2012;90:565–72. [PMC free article: PMC3309205] [PubMed: 22405089]
• Huang SJ, Amendola LM, Sternen DL. Variation among DNA banking consent forms: points for clinicians to bank on. J Community Genet. 2022;13:389-97. [PMC free article: PMC9314484] [PubMed: 35834113]
• Jung EM, Moffat JJ, Liu J, Dravid SM, Gurumurthy CB, Kim WY. Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior. Nat Neurosci. 2017;20:1694-707. [PMC free article: PMC5726525] [PubMed: 29184203]
• Kosho T, Okamoto N, et al Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. Am J Med Genet C Semin Med Genet. 2014;166C:262–75. [PubMed: 25168959]
• Määttänen L, Hietala M, Ignatius J, Arvio M. A 69-year-old woman with Coffin-Siris syndrome. Am J Med Genet A. 2018;176:1764-7. [PubMed: 30055038]
• Machol K, Rousseau J, Ehresmann S, Garcia T, Nguyen TTM, Spillmann RC, Sullivan JA, Shashi V, Jiang YH, Stong N, Fiala E, Willing M, Pfundt R, Kleefstra T, Cho MT, McLaughlin H, Rosello Piera M, Orellana C, Martínez F, Caro-Llopis A, Monfort S, Roscioli T, Nixon CY, Buckley MF, Turner A, Jones WD, van Hasselt PM, Hofstede FC, van Gassen KLI, Brooks AS, van Slegtenhorst MA, Lachlan K, Sebastian J, Madan-Khetarpal S, Sonal D, Sakkubai N, Thevenon J, Faivre L, Maurel A, Petrovski S, Krantz ID, Tarpinian JM, Rosenfeld JA, Lee BH, Campeau PM, et al. Expanding the spectrum of BAF-related disorders: de novo variants in SMARCC2 cause a syndrome with intellectual disability and developmental delay. Am J Hum Genet. 2019;104:164–78. [PMC free article: PMC6323608] [PubMed: 30580808]
• Mannino EA, Miyawaki H, Santen G, Schrier Vergano SA. First data from a parent-reported registry of 81 individuals with Coffin-Siris syndrome: natural history and management recommendations. Am J Med Genet A. 2018;176:2250-8. [PubMed: 30276971]
• Michelson M, Ben-Sasson A, Vinkler C, Leshinsky-Silver E, Netzer I, Frumkin A, Kivity S, Lerman-Sagie T, Lev D. Delineation of the interstitial 6q25 microdeletion syndrome: refinement of the critical causative region. Am J Med Genet A. 2012;158A:1395–9. [PubMed: 22585544]
• Milone R, Gnazzo M, Stefanutti E, Serafin D, Novelli A. A new missense mutation in DPF2 gene related to Coffin Siris syndrome 7: Description of a mild phenotype expanding DPF2-related clinical spectrum and differential diagnosis among similar syndromes epigenetically determined. Brain Dev. 2020;42:192–8. [PubMed: 31706665]
• Nagamani SC, Erez A, Eng C, Ou Z, Chinault C, Workman L, Coldwell J, Stankiewicz P, Patel A, Lupski JR, Cheung SW. Interstitial deletion of 6q25.2-q25.3: a novel microdeletion syndrome associated with microcephaly, developmental delay, dysmorphic features and hearing loss. Eur J Hum Genet. 2009;17:573–81. [PMC free article: PMC2986272] [PubMed: 19034313]
• Ninkovic J, Steiner-Mezzadri A, Jawerka M, Akinci U, Masserdotti G, Petricca S, Fischer J, Von Holst A, Beckers J, Lie CD, Petrik D, Miller E, Tang J, Wu J, Lefebvre V, Demmers J, Eisch A, Metzger D, Crabtree G, Irmler M, Poot R, Gotz M. The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network. Cell Stem Cell. 2013;13:403–18. [PMC free article: PMC4098720] [PubMed: 23933087]
• Nixon KCJ, Rousseau J, Stone MH, Sarikahya M, Ehresmann S, Mizuno S, Matsumoto N, Miyake N, Baralle D, McKee S, Izumi K, Ritter AL, Heide S, Héron D, Depienne C, Titheradge H, Kramer JM, Campeau PM. A syndromic neurodevelopmental disorder caused by mutations in SMARCD1, a core SWI/SNF subunit needed for context-dependent neuronal gene regulation in flies. Am J Hum Genet. 2019;104:596–610. [PMC free article: PMC6451697] [PubMed: 30879640]
• Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-24. [PMC free article: PMC4544753] [PubMed: 25741868]
• Ronan JL, Wu W, Crabtree GR. From neural development to cognition: unexpected roles for chromatin. Nat Rev Genet. 2013;14:347–59. [PMC free article: PMC4010428] [PubMed: 23568486]
• Santen GW, Aten E, Sun Y, Almomani R, Gilissen C, Nielsen M, Kant SG, Snoeck IN, Peeters EA, Hilhorst-Hofstee Y, Wessels MW, Den Hollander NS, Ruivenkamp CA, Van Ommen GJ, Breuning MH, Den Dunnen JT, Van Haeringen A, Kriek M. Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome. Nat Genet. 2012;44:379–80. [PubMed: 22426309]
• Santen GW, Aten E, Vulto-Van Silfhout AT, Pottinger C, Van Bon BW, Van Minderhout IJ, Snowdowne R, Van Der Lans CA, Boogaard M, Linssen MM, Vijfhuizen L, Van Der Wielen MJ, Vollebregt MJ, Coffin-Siris C, Breuning MH, Kriek M, Van Haeringen A, Den Dunnen JT, Hoischen A, Clayton-Smith J, De Vries BB, Hennekam RC, Van Belzen MJ. Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients. Hum Mutat. 2013;34:1519–28. [PubMed: 23929686]
• Santen GW, Clayton-Smith J, et al The ARID1B phenotype: what we have learned so far. Am J Med Genet C Semin Med Genet. 2014;166C:276–89. [PubMed: 25169814]
• Sekiguchi F, Tsurusaki Y, Okamoto N, Teik KW, Mizuno S, Suzumura H, Isidor B, Ong WP, Haniffa M, White SM, Matsuo M, Saito K, Phadke S, Kosho T, Yap P, Goyal M, Clarke LA, Sachdev R, McGillivray G, Leventer RJ, Patel C, Yamagata T, Osaka H, Hisaeda Y, Ohashi H, Shimizu K, Nagasaki K, Hamada J, Dateki S, Sato T, Chinen Y, Awaya T, Kato T, Iwanaga K, Kawai M, Matsuoka T, Shimoji Y, Tan TY, Kapoor S, Gregersen N, Rossi M, Marie-Laure M, McGregor L, Oishi K, Mehta L, Gillies G, Lockhart PJ, Pope K, Shukla A, Girisha KM, Abdel-Salam GMH, Mowat D, Coman D, Kim OH, Cordier MP, Gibson K, Milunsky J, Liebelt J, Cox H, El Chehadeh S, Toutain A, Saida K, Aoi H, Minase G, Tsuchida N, Iwama K, Uchiyama Y, Suzuki T, Hamanaka K, Azuma Y, Fujita A, Imagawa E, Koshimizu E, Takata A, Mitsuhashi S, Miyatake S, Mizuguchi T, Miyake N, Matsumoto N. Genetic abnormalities in a large cohort of Coffin-Siris syndrome patients. J Hum Genet. 2019;64:1173-86. [PubMed: 31530938]
• Schmetz A, Lüdecke HJ, Surowy H, Sivalingam S, Bruel AL, Caumes R, Charles P, Chatron N, Chrzanowska K, Codina-Solà M, Colson C, Cuscó I, Denommé-Pichon AS, Edery P, Faivre L, Green A, Heide S, Hsieh TC, Hustinx A, Kleinendorst L, Knopp C, Kraft F, Krawitz PM, Lasa-Aranzasti A, Lesca G, López-González V, Maraval J, Mignot C, Neuhann T, Netzer C, Oehl-Jaschkowitz B, Petit F, Philippe C, Posmyk R, Putoux A, Reis A, Sánchez-Soler MJ, Suh J, Tkemaladze T, Tran Mau Them F, Travessa A, Trujillano L, Valenzuela I, van Haelst MM, Vasileiou G, Vincent-Delorme C, Walther M, Verde P, Bramswig NC, Wieczorek D. Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals. Hum Genet. 2024;143:71-84. [PubMed: 38117302]
• Schneppenheim R, Fruhwald MC, Gesk S, Hasselblatt M, Jeibmann A, Kordes U, Kreuz M, Leuschner I, Martin Subero JI, Obser T, Oyen F, Vater I, Siebert R. Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Am J Hum Genet. 2010;86:279–84. [PMC free article: PMC2820190] [PubMed: 20137775]
• Schrier SA, Bodurtha JN, Burton B, Chudley AE, Chiong MA, D'avanzo M G, Lynch SA, Musio A, Nyazov DM, Sanchez-Lara PA, Shalev SA, Deardorff MA. The Coffin-Siris syndrome: a proposed diagnostic approach and assessment of 15 overlapping cases. Am J Med Genet A. 2012;158A:1865–76. [PMC free article: PMC3402612] [PubMed: 22711679]
• Schrier Vergano SA. ARID2, a milder cause of Coffin-Siris syndrome? Broadening the phenotype with 17 additional individuals. Am J Med Genet A. 2024;194:e63540. [PubMed: 38243407]
• Trajkova S, Kerkhof J, Rossi Sebastiano M, Pavinato L, Ferrero E, Giovenino C, Carli D, Di Gregorio E, Marinoni R, Mandrile G, Palermo F, Carestiato S, Cardaropoli S, Pullano V, Rinninella A, Giorgio E, Pippucci T, Dimartino P, Rzasa J, Rooney K, McConkey H, Petlichkovski A, Pasini B, Sukarova-Angelovska E, Campbell CM, Metcalfe K, Jenkinson S, Banka S, Mussa A, Ferrero GB, Sadikovic B, Brusco A. DNA methylation analysis in patients with neurodevelopmental disorders improves variant interpretation and reveals complexity. HGG Adv. 2024;5:100309. [PMC free article: PMC11216013] [PubMed: 38751117]
• Tsurusaki Y, Koshimizu E, Ohashi H, Phadke S, Kou I, Shiina M, Suzuki T, Okamoto N, Imamura S, Yamashita M, Watanabe S, Yoshiura K, Kodera H, Miyatake S, Nakashima M, Saitsu H, Ogata K, Ikegawa S, Miyake N, Matsumoto N. De novo SOX11 mutations cause Coffin-Siris syndrome. Nat Commun. 2014a;5:4011. [PubMed: 24886874]
• Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet. 2012;44:376–8. [PubMed: 22426308]
• Tsurusaki Y, Okamoto N, Ohashi H, Mizuno S, Matsumoto N, Makita Y, Fukuda M, Isidor B, Perrier J, Aggarwal S, Dalal AB, Al-Kindy A, Liebelt J, Mowat D, Nakashima M, Saitsu H, Miyake N, Matsumoto N. Coffin-Siris syndrome is a SWI/SNF complex disorder. Clin Genet. 2014b;85:548–54. [PubMed: 23815551]
• Tu Y, Fang C, Xu J, Zhou Y, Liang M, Yang Z. A de novo variant of BICRA results in Coffin-Siris syndrome 12. Mol Genet Genomic Med. 2023;11:e2250. [PMC free article: PMC10655513] [PubMed: 37485815]
• van der Sluijs PJ, Alders M, Dingemans AJM, Parbhoo K, van Bon BW, Dempsey JC, Doherty D, den Dunnen JT, Gerkes EH, Milller IM, Moortgat S, Regier DS, Ruivenkamp CAL, Schmalz B, Smol T, Stuurman KE, Vincent-Delorme C, de Vries BBA, Sadikovic B, Hickey SE, Rosenfeld JA, Maystadt I, Santen GWE. A case series of familial ARID1B variants illustrating variable expression and suggestions to update the ACMG criteria. Genes (Basel). 2021;12:1275. [PMC free article: PMC8393241] [PubMed: 34440449]
• van der Sluijs PJ, Gösgens M, Dingemans AJM, Striano P, Riva A, Mignot C, Faudet A, Vasileiou G, Walther M, Schrier Vergano SA, Alders M, Alkuraya FS, Alorainy I, Alsaif HS, Anderlid B, Bache I, van Beek I, Blanluet M, van Bon BW, Brunet T, Brunner H, Carriero ML, Charles P, Chatron N, Coccia E, Dubourg C, Earl RK, Eichler EE, Faivre L, Foulds N, Graziano C, Guerrot AM, Hashem MO, Heide S, Heron D, Hickey SE, Hopman SMJ, Kattentidt-Mouravieva A, Kerkhof J, Klein Wassink-Ruiter JS, Kurtz-Nelson EC, Kušíková K, Kvarnung M, Lecoquierre F, Leszinski GS, Loberti L, Magoulas PL, Mari F, Maystadt I, Merla G, Milunsky JM, Moortgat S, Nicolas G, Leary MO', Odent S, Ozmore JR, Parbhoo K, Pfundt R, Piccione M, Pinto AM, Popp B, Putoux A, Rehm HL, Reis A, Renieri A, Rosenfeld JA, Rossi M, Salzano E, Saugier-Veber P, Seri M, Severi G, Sonmez FM, Strobl-Wildemann G, Stuurman KE, Uctepe E, Van Esch H, Vitetta G, de Vries BBA, Wahl D, Wang T, Zacher P, Heitink KR, Ropers FG, Steenbeek D, Rybak T, Santen GWE. ARID1B-related disorder in 87 adults: natural history and self-sustainability. Genet Med Open. 2024;2:101873. [PMC free article: PMC11613905] [PubMed: 39669611]
• van der Sluijs PJ, Safai Pour K, Berends CL, Kruizinga MD, Müller AR, van Eeghen AM, Rodríguez-Girondo M, Juachon MJ, Steenbeek D, Cohen AF, Zuiker RGJA, Santen GWE. Clonazepam repurposing in ARID1B patients through conventional RCT and N-of-1 trials: an experimental strategy for orphan disease development. J Med Genet. 2025;62:210-18. [PMC free article: PMC11877031] [PubMed: 39740803]
• van der Sluijs PJ, Vergano SA, Roeder ER, Jongmans MCJ, Santen GWE. Recommending revised hepatoblastoma surveillance in children with a pathogenic ARID1A variant. Reply to "Cancer in ARID1A-Coffin-Siris syndrome: review and report of a child with hepatoblastoma" by Cárcamo et al. 2022. Eur J Med Genet. 2023;66:104694. [PubMed: 36592690]
• Van Houdt JK, Nowakowska BA, Sousa SB, Van Schaik BD, Seuntjens E, Avonce N, Sifrim A, Abdul-Rahman OA, Van Den Boogaard MJ, Bottani A, Castori M, Cormier-Daire V, Deardorff MA, Filges I, Fryer A, Fryns JP, Gana S, Garavelli L, Gillessen-Kaesbach G, Hall BD, Horn D, Huylebroeck D, Klapecki J, Krajewska-Walasek M, Kuechler A, Lines MA, Maas S, Macdermot KD, Mckee S, Magee A, De Man SA, Moreau Y, Morice-Picard F, Obersztyn E, Pilch J, Rosser E, Shannon N, Stolte-Dijkstra I, Van Dijck P, Vilain C, Vogels A, Wakeling E, Wieczorek D, Wilson L, Zuffardi O, Van Kampen AH, Devriendt K, Hennekam R, Vermeesch JR. Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nat Genet. 2012;44:445–9. [PubMed: 22366787]
• Vasileiou G, Vergarajauregui S, Endele S, Popp B, Büttner C, Ekici A, Gerard M, Bramswig N, Albrecht B, Clayton-Smith J, Morton J, Tomkins S, Low K, Weber A, Wenzel M, Altmüller J, Li Y. Bernd Wollnik, George Hoganson, Maria-Renée Plona, Megan T. Cho, Christian T. Thiel, Lüdecke H, Strom T, Calpena E, Wilkie A, Wieczorek D, Engel F, Reis A. Mutations in the BAF-complex subunit DPF2 are associated with Coffin-Siris syndrome. Am J Hum Genet. 2018;102:468–79. [PMC free article: PMC5985265] [PubMed: 29429572]
• Vasko A, Schrier Vergano SA. Language impairments in individuals with Coffin-Siris syndrome. Front Neurosci. 2022;15:802583. [PMC free article: PMC8811135] [PubMed: 35126043]
• Vengoechea J, Carpenter L, Zarate YA. Papillary thyroid cancer in a patient with interstitial 6q25 deletion including ARID1B. Am J Med Genet A. 2014;164A:1857–9. [PubMed: 24700687]
• Vogt J, Ryan E, Tischkowitz MD, Reardon W, Brueton LA. The tale of a nail sign in chromosome 4q34 deletion syndrome. Clin Dysmorphol. 2006;15:127-32. [PubMed: 16760729]
• Wieczorek D, Bogershausen N, Beleggia F, Steiner-Haldenstatt S, Pohl E, Li Y, Milz E, Martin M, Thiele H, Altmuller J, Alanay Y, Kayserili H, Klein-Hitpass L, Bohringer S, Wollstein A, Albrecht B, Boduroglu K, Caliebe A, Chrzanowska K, Cogulu O, Cristofoli F, Czeschik JC, Devriendt K, Dotti MT, Elcioglu N, Gener B, Goecke TO, Krajewska-Walasek M, Guillen-Navarro E, Hayek J, Houge G, Kilic E, Simsek-Kiper PO, Lopez-Gonzalez V, Kuechler A, Lyonnet S, Mari F, Marozza A, Mathieu Dramard M, Mikat B, Morin G, Morice-Picard F, Ozkinay F, Rauch A, Renieri A, Tinschert S, Utine GE, Vilain C, Vivarelli R, Zweier C, Nurnberg P, Rahmann S, Vermeesch J, Ludecke HJ, Zeschnigk M, Wollnik B. A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling. Hum Mol Genet. 2013;22:5121–35. [PubMed: 23906836]
• Zawerton A, Yao B, Yeager JP, Pippucci T, Haseeb A, Smith JD, Wischmann L, Kühl SJ, Dean JCS, Pilz DT, Holder SE, McNeill A, Graziano C, Lefebvre V, et al De novo SOX4 variants cause a neurodevelopmental disease associated with mild dysmorphism. Am J Hum Genet. 2019;104:246–59. [published correction appears in Am J Hum Genet. 2019;104:777] [PMC free article: PMC6369454] [PubMed: 30661772]
• Zweier C, Kraus C, Brueton L, Cole T, Degenhardt F, Engels H, Gillessen-Kaesbach G, Graul-Neumann L, Horn D, Hoyer J, Just W, Rauch A, Reis A, Wollnik B, Zeschnigk M, Ludecke HJ, Wieczorek D. A new face of Borjeson-Forssman-Lehmann syndrome? De novo mutations in PHF6 in seven females with a distinct phenotype. J Med Genet. 2013;50:838–47. [PubMed: 24092917]