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Coffin-Siris syndrome 8(CSS8)

MedGen UID:
1679527
Concept ID:
C5193054
Disease or Syndrome
Synonyms: COFFIN-SIRIS SYNDROME 8; CSS8
 
Gene (location): SMARCC2 (12q13.2)
 
Monarch Initiative: MONDO:0032702
OMIM®: 618362

Disease characteristics

Excerpted from the GeneReview: Coffin-Siris Syndrome
Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies can include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings commonly include feeding difficulties, slow growth, ophthalmologic abnormalities, and hearing impairment. [from GeneReviews]
Authors:
Samantha Schrier Vergano  |  Gijs Santen  |  Dagmar Wieczorek, et. al.   view full author information

Additional description

From OMIM
Coffin-Siris syndrome-8 (CSS8) is characterized by variable degrees of impaired intellectual development including speech impairment, hypotonia, feeding difficulties, and behavioral abnormalities. Dysmorphic features may or may not be present and include hypertrichosis or thin scalp hair, thick eyebrows, thin upper vermilion, and upturned nose (Machol et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).  http://www.omim.org/entry/618362

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
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.
Poor suck
MedGen UID:
324693
Concept ID:
C1837142
Finding
An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
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.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Finding
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
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.
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.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
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.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Eczematoid dermatitis
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
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).
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
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.
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).
Hypertrichosis
MedGen UID:
43787
Concept ID:
C0020555
Disease or Syndrome
Hypertrichosis is increased hair growth that is abnormal in quantity or location.
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

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
Genes (Basel) 2021 Aug 20;12(8) doi: 10.3390/genes12081275. PMID: 34440449Free PMC Article

Recent clinical studies

Etiology

Wu R, Tang W, Li P, Meng Z, Li X, Liang L
Am J Med Genet A 2024 Aug;194(8):e63626. Epub 2024 Apr 9 doi: 10.1002/ajmg.a.63626. PMID: 38591849
Belanger Deloge R, Zhao X, Luna PN, Shaw CA, Rosenfeld JA, Scott DA
Eur J Hum Genet 2023 Mar;31(3):296-303. Epub 2022 Dec 6 doi: 10.1038/s41431-022-01255-y. PMID: 36474027Free PMC Article
Cárcamo B, Masotto B, Baquero-Vaquer A, Ceballos-Saenz D, Zapata-Aldana E
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Brain Dev 2015 May;37(5):527-36. Epub 2014 Sep 22 doi: 10.1016/j.braindev.2014.08.009. PMID: 25249037

Diagnosis

Houb-Dine A, Jalila H, Zaoui F, Benkaddour A
Tunis Med 2023 Apr 5;101(4):456-459. PMID: 38372531Free PMC Article
Gofin Y, Zhao X, Gerard A, Scaglia F, Wangler MF, Schrier Vergano SA, Scott DA
Am J Med Genet A 2022 Sep;188(9):2718-2723. Epub 2022 Jul 7 doi: 10.1002/ajmg.a.62889. PMID: 35796094Free PMC Article
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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

Prognosis

Kaname T, Yanagi K
J Hum Genet 2017 Aug;62(8):739-740. Epub 2017 Jun 1 doi: 10.1038/jhg.2017.58. PMID: 28566769Free PMC Article
Miyatake S, Okamoto N, Stark Z, Nabetani M, Tsurusaki Y, Nakashima M, Miyake N, Mizuguchi T, Ohtake A, Saitsu H, Matsumoto N
J Hum Genet 2017 Aug;62(8):741-746. Epub 2017 Mar 2 doi: 10.1038/jhg.2017.24. PMID: 28250421Free PMC Article
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Clinical prediction guides

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
Yi S, Li M, Yang Q, Qin Z, Yi S, Xu J, Chen J, Wei H, Jiang Y, Wei R, Zhang Q, Yang C, Chen B, Luo J
J Mol Neurosci 2022 Jun;72(6):1293-1299. Epub 2022 May 10 doi: 10.1007/s12031-022-02010-0. PMID: 35536477
Lee Y, Choi Y, Seo GH, Kim GH, Keum C, Kim YM, Do HS, Choi J, Choi IH, Yoo HW, Lee BH
BMC Med Genomics 2021 Oct 27;14(1):254. doi: 10.1186/s12920-021-01104-9. PMID: 34706719Free PMC Article
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
Genes (Basel) 2021 Aug 20;12(8) doi: 10.3390/genes12081275. PMID: 34440449Free PMC Article
Knapp KM, Poke G, Jenkins D, Truter W, Bicknell LS
Am J Med Genet A 2019 Aug;179(8):1637-1641. Epub 2019 Jun 17 doi: 10.1002/ajmg.a.61262. PMID: 31207137

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