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Coffin-Siris syndrome 11(CSS11)

MedGen UID:
1717402
Concept ID:
C5241442
Disease or Syndrome
Synonyms: COFFIN-SIRIS SYNDROME 11; CSS11
 
Gene (location): SMARCD1 (12q13.12)
 
Monarch Initiative: MONDO:0032912
OMIM®: 618779

Definition

Coffin-Siris syndrome-11 (CSS11) is a syndromic neurodevelopmental disorder characterized by global developmental delay and impaired intellectual development associated with hypotonia, feeding difficulties, and variable dysmorphic features. Most patients have distal anomalies, such as small hands and feet and hypoplastic fifth toenails (summary by Nixon et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900). [from OMIM]

Clinical features

From HPO
Small hand
MedGen UID:
108279
Concept ID:
C0575802
Finding
Disproportionately small hand.
Esophageal atresia
MedGen UID:
4545
Concept ID:
C0014850
Congenital Abnormality
A developmental defect resulting in complete obliteration of the lumen of the esophagus such that the esophagus ends in a blind pouch rather than connecting to the stomach.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Uplifted earlobe
MedGen UID:
344655
Concept ID:
C1856117
Anatomical Abnormality
An abnormal orientation of the earlobes such that they point out- and upward. That is, the lateral surface of ear lobe faces superiorly.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Vertical bony ridge positioned in the midline of the forehead.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Cleft soft palate
MedGen UID:
98471
Concept ID:
C0432098
Congenital Abnormality
Cleft of the soft palate (also known as the velum, or muscular palate) as a result of a developmental defect occurring between the 7th and 12th week of pregnancy. Cleft soft palate can cause functional abnormalities of the Eustachian tube with resulting middle ear anomalies and hearing difficulties, as well as speech problems associated with hypernasal speech due to velopharyngeal insufficiency.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Low posterior hairline
MedGen UID:
383755
Concept ID:
C1855728
Finding
Hair on the neck extends more inferiorly than usual.
Downturned corners of mouth
MedGen UID:
356471
Concept ID:
C1866195
Anatomical Abnormality
A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Professional guidelines

PubMed

Mannino EA, Miyawaki H, Santen G, Schrier Vergano SA
Am J Med Genet A 2018 Nov;176(11):2250-2258. Epub 2018 Oct 1 doi: 10.1002/ajmg.a.40471. PMID: 30276971
Kosho T, Okamoto N; Coffin-Siris Syndrome International Collaborators
Am J Med Genet C Semin Med Genet 2014 Sep;166C(3):262-75. Epub 2014 Aug 28 doi: 10.1002/ajmg.c.31407. PMID: 25168959
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 consortium, Breuning MH, Kriek M, van Haeringen A, den Dunnen JT, Hoischen A, Clayton-Smith J, de Vries BB, Hennekam RC, van Belzen MJ
Hum Mutat 2013 Nov;34(11):1519-28. Epub 2013 Aug 30 doi: 10.1002/humu.22394. PMID: 23929686

Recent clinical studies

Etiology

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
Genet Med 2023 Nov;25(11):100950. Epub 2023 Aug 5 doi: 10.1016/j.gim.2023.100950. PMID: 37551667
Cárcamo B, Masotto B, Baquero-Vaquer A, Ceballos-Saenz D, Zapata-Aldana E
Eur J Med Genet 2022 Nov;65(11):104600. Epub 2022 Aug 29 doi: 10.1016/j.ejmg.2022.104600. PMID: 36049608
Angelozzi M, Karvande A, Molin AN, Ritter AL, Leonard JMM, Savatt JM, Douglass K, Myers SM, Grippa M, Tolchin D, Zackai E, Donoghue S, Hurst ACE, Descartes M, Smith K, Velasco D, Schmanski A, Crunk A, Tokita MJ, de Lange IM, van Gassen K, Robinson H, Guegan K, Suri M, Patel C, Bournez M, Faivre L, Tran-Mau-Them F, Baker J, Fabie N, Weaver K, Shillington A, Hopkin RJ, Barge-Schaapveld DQCM, Ruivenkamp CA, Bökenkamp R, Vergano S, Seco Moro MN, Díaz de Bustamante A, Misra VK, Kennelly K, Rogers C, Friedman J, Wigby KM, Lenberg J, Graziano C, Ahrens-Nicklas RC, Lefebvre V
J Med Genet 2022 Nov;59(11):1058-1068. Epub 2022 Mar 1 doi: 10.1136/jmedgenet-2021-108375. PMID: 35232796Free PMC Article
Lomelí H, Castillo-Robles J
FEBS Lett 2016 Jun;590(11):1555-69. Epub 2016 May 20 doi: 10.1002/1873-3468.12201. PMID: 27149204
Santen GW, Kriek M, van Attikum H
Epigenetics 2012 Nov;7(11):1219-24. Epub 2012 Sep 25 doi: 10.4161/epi.22299. PMID: 23010866Free PMC Article

Diagnosis

Tu Y, Fang C, Xu J, Zhou Y, Liang M, Yang Z
Mol Genet Genomic Med 2023 Nov;11(11):e2250. Epub 2023 Jul 24 doi: 10.1002/mgg3.2250. PMID: 37485815Free PMC Article
Xia D, Deng S, Gao C, Li X, Zhang L, Xiao X, Peng X, Zhang J, He Z, Meng Z, Liu Z, Ouyang N, Liang L
Am J Med Genet A 2023 May;191(5):1240-1249. Epub 2023 Feb 9 doi: 10.1002/ajmg.a.63139. PMID: 36756859
Diel H, Ding C, Grehn F, Chronopoulos P, Bartsch O, Hoffmann EM
BMC Ophthalmol 2021 Jan 11;21(1):28. doi: 10.1186/s12886-020-01788-0. PMID: 33430815Free PMC Article
Mari F, Marozza A, Mencarelli MA, Lo Rizzo C, Fallerini C, Dosa L, Di Marco C, Carignani G, Baldassarri M, Cianci P, Vivarelli R, Vascotto M, Grosso S, Rubegni P, Caffarelli C, Pretegiani E, Fimiani M, Garavelli L, Cristofoli F, Vermeesch JR, Nuti R, Dotti MT, Balestri P, Hayek J, Selicorni A, Renieri A
Brain Dev 2015 May;37(5):527-36. Epub 2014 Sep 22 doi: 10.1016/j.braindev.2014.08.009. PMID: 25249037
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 consortium, Breuning MH, Kriek M, van Haeringen A, den Dunnen JT, Hoischen A, Clayton-Smith J, de Vries BB, Hennekam RC, van Belzen MJ
Hum Mutat 2013 Nov;34(11):1519-28. Epub 2013 Aug 30 doi: 10.1002/humu.22394. PMID: 23929686

Prognosis

Angelozzi M, Karvande A, Molin AN, Ritter AL, Leonard JMM, Savatt JM, Douglass K, Myers SM, Grippa M, Tolchin D, Zackai E, Donoghue S, Hurst ACE, Descartes M, Smith K, Velasco D, Schmanski A, Crunk A, Tokita MJ, de Lange IM, van Gassen K, Robinson H, Guegan K, Suri M, Patel C, Bournez M, Faivre L, Tran-Mau-Them F, Baker J, Fabie N, Weaver K, Shillington A, Hopkin RJ, Barge-Schaapveld DQCM, Ruivenkamp CA, Bökenkamp R, Vergano S, Seco Moro MN, Díaz de Bustamante A, Misra VK, Kennelly K, Rogers C, Friedman J, Wigby KM, Lenberg J, Graziano C, Ahrens-Nicklas RC, Lefebvre V
J Med Genet 2022 Nov;59(11):1058-1068. Epub 2022 Mar 1 doi: 10.1136/jmedgenet-2021-108375. PMID: 35232796Free PMC Article
Slavotinek A, Lefebvre M, Brehin AC, Thauvin C, Patrier S, Sparks TN, Norton M, Yu J, Huang E
Eur J Med Genet 2022 Feb;65(2):104407. Epub 2021 Dec 20 doi: 10.1016/j.ejmg.2021.104407. PMID: 34942405Free PMC Article
Bina M
BMC Genomics 2020 May 31;21(1):378. doi: 10.1186/s12864-020-6688-8. PMID: 32475352Free PMC Article
Pranckėnienė L, Siavrienė E, Gueneau L, Preikšaitienė E, Mikštienė V, Reymond A, Kučinskas V
Mol Genet Genomic Med 2019 Dec;7(12):e1006. Epub 2019 Oct 19 doi: 10.1002/mgg3.1006. PMID: 31628733Free PMC Article
Lomelí H, Castillo-Robles J
FEBS Lett 2016 Jun;590(11):1555-69. Epub 2016 May 20 doi: 10.1002/1873-3468.12201. PMID: 27149204

Clinical prediction guides

Xia D, Deng S, Gao C, Li X, Zhang L, Xiao X, Peng X, Zhang J, He Z, Meng Z, Liu Z, Ouyang N, Liang L
Am J Med Genet A 2023 May;191(5):1240-1249. Epub 2023 Feb 9 doi: 10.1002/ajmg.a.63139. PMID: 36756859
Angelozzi M, Karvande A, Molin AN, Ritter AL, Leonard JMM, Savatt JM, Douglass K, Myers SM, Grippa M, Tolchin D, Zackai E, Donoghue S, Hurst ACE, Descartes M, Smith K, Velasco D, Schmanski A, Crunk A, Tokita MJ, de Lange IM, van Gassen K, Robinson H, Guegan K, Suri M, Patel C, Bournez M, Faivre L, Tran-Mau-Them F, Baker J, Fabie N, Weaver K, Shillington A, Hopkin RJ, Barge-Schaapveld DQCM, Ruivenkamp CA, Bökenkamp R, Vergano S, Seco Moro MN, Díaz de Bustamante A, Misra VK, Kennelly K, Rogers C, Friedman J, Wigby KM, Lenberg J, Graziano C, Ahrens-Nicklas RC, Lefebvre V
J Med Genet 2022 Nov;59(11):1058-1068. Epub 2022 Mar 1 doi: 10.1136/jmedgenet-2021-108375. PMID: 35232796Free PMC Article
Slavotinek A, Lefebvre M, Brehin AC, Thauvin C, Patrier S, Sparks TN, Norton M, Yu J, Huang E
Eur J Med Genet 2022 Feb;65(2):104407. Epub 2021 Dec 20 doi: 10.1016/j.ejmg.2021.104407. PMID: 34942405Free PMC Article
Diel H, Ding C, Grehn F, Chronopoulos P, Bartsch O, Hoffmann EM
BMC Ophthalmol 2021 Jan 11;21(1):28. doi: 10.1186/s12886-020-01788-0. PMID: 33430815Free PMC Article
Errichiello E, Mustafa N, Vetro A, Notarangelo LD, de Jonge H, Rinaldi B, Vergani D, Giglio SR, Morbini P, Zuffardi O
J Pathol 2017 Sep;243(1):9-15. Epub 2017 Jul 25 doi: 10.1002/path.4926. PMID: 28608987Free PMC Article

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