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Coffin-Siris syndrome 5(CSS5)

MedGen UID:
934755
Concept ID:
C4310788
Disease or Syndrome
Synonym: CSS5
 
Gene (location): SMARCE1 (17q21.2)
 
Monarch Initiative: MONDO:0014838
OMIM®: 616938

Definition

Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly (summary by Wieczorek et al., 2013). Patients with SMARCE1 mutations have a wide spectrum of manifestations, including severe to moderate intellectual disability and heart defects (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900). [from OMIM]

Clinical features

From HPO
Arachnodactyly
MedGen UID:
2047
Concept ID:
C0003706
Congenital Abnormality
Abnormally long and slender fingers (spider fingers).
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Sandal gap
MedGen UID:
374376
Concept ID:
C1840069
Finding
A widely spaced gap between the first toe (the great toe) and the second toe.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
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.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
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.
Dandy-Walker malformation
MedGen UID:
419183
Concept ID:
C2931867
Congenital Abnormality
A congenital brain malformation typically characterized by incomplete formation of the cerebellar vermis, dilation of the fourth ventricle, and enlargement of the posterior fossa. In layman's terms, Dandy Walker malformation is a cyst in the cerebellum (typically symmetrical) that is involved with the fourth ventricle. This may interfere with the ability to drain cerebrospinal fluid from the brain, resulting in hydrocephalus. Dandy Walker cysts are formed during early embryonic development, while the brain forms. The cyst in the cerebellum typically has several blood vessels running through it connecting to the brain, thereby prohibiting surgical removal.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
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).
Wide nose
MedGen UID:
140869
Concept ID:
C0426421
Finding
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
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.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Low anterior hairline
MedGen UID:
331280
Concept ID:
C1842366
Finding
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella.
Thick nasal alae
MedGen UID:
335032
Concept ID:
C1844809
Finding
Increase in bulk of the ala nasi.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of hairs per unit area of skin of the scalp.
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Dystrophic toenail
MedGen UID:
318813
Concept ID:
C1833225
Finding
Toenail changes apart from changes of the color of the toenail (nail dyschromia) that involve partial or complete disruption of the various keratinous layers of the nail plate.
Hypoplastic toenails
MedGen UID:
332409
Concept ID:
C1837279
Finding
Underdevelopment of the toenail.
Long eyelashes
MedGen UID:
342955
Concept ID:
C1853738
Finding
Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective).
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Professional guidelines

PubMed

Yu QX, Jing XY, Lin XM, Zhen L, Li DZ
Prenat Diagn 2022 Nov;42(12):1488-1492. Epub 2022 Jul 18 doi: 10.1002/pd.6213. PMID: 35801292

Recent clinical studies

Etiology

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
Hum Genet 2024 Jan;143(1):71-84. Epub 2023 Dec 20 doi: 10.1007/s00439-023-02622-5. PMID: 38117302
Yu QX, Jing XY, Lin XM, Zhen L, Li DZ
Prenat Diagn 2022 Nov;42(12):1488-1492. Epub 2022 Jul 18 doi: 10.1002/pd.6213. PMID: 35801292
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
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
Nat Commun 2014 Jun 2;5:4011. doi: 10.1038/ncomms5011. PMID: 24886874
Ueda K, Saito A, Nakano H, Iinuma K
Helv Paediatr Acta 1980 Sep;35(4):385-90. PMID: 7192700

Diagnosis

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
Hum Genet 2024 Jan;143(1):71-84. Epub 2023 Dec 20 doi: 10.1007/s00439-023-02622-5. PMID: 38117302
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
Ciliberto M, Skjei K, Vasko A, Schrier Vergano S
Am J Med Genet A 2023 Jan;191(1):22-28. Epub 2022 Sep 30 doi: 10.1002/ajmg.a.62979. PMID: 36177969
Yu QX, Jing XY, Lin XM, Zhen L, Li DZ
Prenat Diagn 2022 Nov;42(12):1488-1492. Epub 2022 Jul 18 doi: 10.1002/pd.6213. PMID: 35801292
Curcio MR, Ferranti S, Lotti F, Grosso S
Neurol Sci 2021 Feb;42(2):727-729. Epub 2020 Oct 2 doi: 10.1007/s10072-020-04782-y. PMID: 33006724

Therapy

Jancewicz I, Siedlecki JA, Sarnowski TJ, Sarnowska E
Epigenetics Chromatin 2019 Nov 13;12(1):68. doi: 10.1186/s13072-019-0315-4. PMID: 31722744Free PMC Article

Prognosis

Zhou M, Wang F, Dai Q, Dou J, Wu Y, Zhu Y
Clin Oral Investig 2024 Apr 30;28(5):287. doi: 10.1007/s00784-024-05659-6. PMID: 38684576
Demily C, Duwime C, Lopez C, Hemimou C, Poisson A, Plasse J, Robert MP, Dénier C, Rossi M, Franck N, Besmond C, Barcia G, Boddaert N, Munnich A, Vaivre-Douret L
Psychiatr Genet 2019 Dec;29(6):237-242. doi: 10.1097/YPG.0000000000000225. PMID: 30933046
Sweeney NM, Nahas SA, Chowdhury S, Campo MD, Jones MC, Dimmock DP, Kingsmore SF; RCIGM Investigators
Cold Spring Harb Mol Case Stud 2018 Jun;4(3) Epub 2018 Jun 1 doi: 10.1101/mcs.a002469. PMID: 29549119Free PMC Article
Suzumura H, Sakurai K, Kano K, Ichimura T
Acta Paediatr Jpn 1996 Oct;38(5):537-40. doi: 10.1111/j.1442-200x.1996.tb03541.x. PMID: 8942018
Ueda K, Saito A, Nakano H, Iinuma K
Helv Paediatr Acta 1980 Sep;35(4):385-90. PMID: 7192700

Clinical prediction guides

Zhou M, Wang F, Dai Q, Dou J, Wu Y, Zhu Y
Clin Oral Investig 2024 Apr 30;28(5):287. doi: 10.1007/s00784-024-05659-6. PMID: 38684576
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
van der Sluijs PJ, Joosten M, Alby C, Attié-Bitach T, Gilmore K, Dubourg C, Fradin M, Wang T, Kurtz-Nelson EC, Ahlers KP, Arts P, Barnett CP, Ashfaq M, Baban A, van den Born M, Borrie S, Busa T, Byrne A, Carriero M, Cesario C, Chong K, Cueto-González AM, Dempsey JC, Diderich KEM, Doherty D, Farholt S, Gerkes EH, Gorokhova S, Govaerts LCP, Gregersen PA, Hickey SE, Lefebvre M, Mari F, Martinovic J, Northrup H, O'Leary M, Parbhoo K, Patrier S, Popp B, Santos-Simarro F, Stoltenburg C, Thauvin-Robinet C, Thompson E, Vulto-van Silfhout AT, Zahir FR, Scott HS, Earl RK, Eichler EE, Vora NL, Wilnai Y, Giordano JL, Wapner RJ, Rosenfeld JA, Haak MC, Santen GWE
Genet Med 2022 Aug;24(8):1753-1760. Epub 2022 May 18 doi: 10.1016/j.gim.2022.04.010. PMID: 35579625Free PMC Article
Demily C, Duwime C, Lopez C, Hemimou C, Poisson A, Plasse J, Robert MP, Dénier C, Rossi M, Franck N, Besmond C, Barcia G, Boddaert N, Munnich A, Vaivre-Douret L
Psychiatr Genet 2019 Dec;29(6):237-242. doi: 10.1097/YPG.0000000000000225. PMID: 30933046
Swillen A, Glorieux N, Peeters M, Fryns JP
Clin Genet 1995 Oct;48(4):177-82. doi: 10.1111/j.1399-0004.1995.tb04084.x. PMID: 8591667

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