There had been 31 reported cases by 1991.[1] The number of occurrences since then has grown and is now reported to be around 80.[2] The differential includes Nicolaides–Baraitser syndrome.[3] Presentation[edit] mild to severe intellectual disability,[ [en.wikipedia.org]

In the presented case both of these symptoms, infections and feeding problems were present. [ispub.com]

Tsurusaki Y...Matsumoto N 24886874 2014 8 Hypertrichosis, hyperkeratosis, abnormal corpus callosum, mental retardation and dysmorphic features in three unrelated females. 56 6 Poyhonen MH...Kaariainen HA 15057123 2004 9 Coffin-Siris syndrome: review and presentation [malacards.org]

Hypoplastic fifth toenails were present in all patients. Permission has been obtained from the patient’s parents and mother (3) herself for presentation. [nature.com]

• Disability

  24 56 6 Hoyer J...Reis A 22405089 2012 6 The HHID syndrome of hypertrichosis, hyperkeratosis, abnormal corpus callosum, intellectual disability, and minor anomalies is caused by mutations in ARID1B. 56 6 Zweier M...Rauch A 28323383 2017 7 De novo SOX11 [malacards.org]

  "Extending the clinical and genetic spectrum of ARID2 related intellectual disability. A case series of 7 patients" (PDF). European Journal of Medical Genetics. 62 (1): 27–34. doi:10.1016/j.ejmg.2018.04.014. PMID 29698805. [en.wikipedia.org]

  ARID2 Most individuals with ARID2 pathogenic variants demonstrate intellectual disability, hypotonia, and behavioral anomalies. Birth defects are not common. [fdna.health]

  Most affected individuals have mild to severe intellectual disability or delayed development of speech and motor skills such as sitting and walking. [ghr.nlm.nih.gov]

  CSS is not progressive, so her conditions will not get worse, but because of her intellectual disabilities she most likely will not be able to drive a car or live on her own. [chop.edu]

• Developmental Delay

  delays and absent fifth finger and toe nails. [en.wikipedia.org]

  delay. 61 24 Malli T...Webersinke G 25250687 2014 46 Numerous BAF complex genes are mutated in Coffin-Siris syndrome. 61 24 Miyake N...Matsumoto N 25081545 2014 47 Coffin-Siris syndrome and related disorders involving components of the BAF (mSWI/SNF) [malacards.org]

  Furthermore, variants in proteins containing PHD fingers, motifs recognizing specific histone tail modifications, have been associated with several neurological and developmental-delay disorders. [hal.archives-ouvertes.fr]

  Some of the characteristics of CSS that Julia had include global developmental delays, delayed milestones, intellectual disability, a shortened pinky finger and/or toe nail, and hypotonia (low tone). [chop.edu]

  The phenotype of all described patients with SOX11 variants (in the HMG domain) shows that 100 % of the individuals have developmental delay and hypoplastic fifth toenails. There is a variation in the degree of developmental delay. [nature.com]

• Coarse Facial Features

  facial features, including wide nose, wide mouth, and thick eyebrows and lashes Causes[edit] Autosomal dominant inheritance is the most likely, usually by de novo mutation. [en.wikipedia.org]

  facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. [flybase.org]

  Affected individuals share common clinical features described in individuals with Coffin-Siris syndrome, including coarse facial features, global developmental delay, intellectual disability, speech impairment, and hypoplasia of fingernails and toenails [hal.archives-ouvertes.fr]

  This condition, besides macrocephaly, may present: coarse facial features with wide mouth, developmental delay with seizures, umbilical hernia and nail hypoplasia as features. [ispub.com]

  Characteristic major features include mild to severe developmental or cognitive delay (in all patients), fifth finger nail/distal phalanx hypoplasia or aplasia (almost all patients at birth), and coarse facial features (commonly observed over time). [orpha.net]

• Feeding Difficulties

  […] around 80.[2] The differential includes Nicolaides–Baraitser syndrome.[3] Presentation[edit] mild to severe intellectual disability,[4][5] also called "developmental disability"[6] short fifth digits with hypoplastic or absent nails low birth weight feeding [en.wikipedia.org]

  Also typical, mostly in infancy and childhood, are feeding difficulties. In the presented case both of these symptoms, infections and feeding problems were present. [ispub.com]

  Common minor findings include short stature, failure to thrive, feeding difficulties, microcephaly, ophthalmological manifestations (cataracts, ptosis, strabismus), cardiac anomalies (ventricular septal/atrial septal defects, tetralogy of Fallot, patent [orpha.net]

  Individuals are typically small for gestational age and have postnatal short stature and severe microcephaly, complex congenital heart defects and feeding difficulties. [fdna.health]

• Short Stature

  Coffin–Siris syndrome Other names Dwarfism-Onychodysplasia, Fifth Digit Syndrome, Mental Retardation with Hypoplastic 5th Fingernails and Toenails, Short Stature-Onychodysplasia Coffin–Siris syndrome is inherited in an autosomal dominant manner Coffin–Siris [en.wikipedia.org]

  Other signs and symptoms that may occur in people with this condition include short stature, low muscle tone (hypotonia), and abnormally loose (lax) joints. Abnormalities of the eyes, brain, heart, and kidneys may also be present. [ghr.nlm.nih.gov]

  Other Names for This Condition Dwarfism-onychodysplasia Fifth digit syndrome Mental retardation with hypoplastic fifth fingernails and toenails Short stature-onychodysplasia References Euskirchen G, Auerbach RK, Snyder M. [medlineplus.gov]

  Common minor findings include short stature, failure to thrive, feeding difficulties, microcephaly, ophthalmological manifestations (cataracts, ptosis, strabismus), cardiac anomalies (ventricular septal/atrial septal defects, tetralogy of Fallot, patent [orpha.net]

  Individuals are typically small for gestational age and have postnatal short stature and severe microcephaly, complex congenital heart defects and feeding difficulties. [fdna.health]

• Hepatomegaly

  "Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene". European Journal of Human Genetics. 22 (11): 1327–9. doi:10.1038/ejhg.2014.25. PMC 4200437. PMID 24569609. [en.wikipedia.org]

  However, unlike other patients described, she has extreme macrocephaly, obesity with hepatomegaly, PCOS, hyperinsulinism and metabolic syndrome. [nature.com]

• Macrocephaly

  "Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene". European Journal of Human Genetics. 22 (11): 1327–9. doi:10.1038/ejhg.2014.25. PMC 4200437. PMID 24569609. [en.wikipedia.org]

  This condition, besides macrocephaly, may present: coarse facial features with wide mouth, developmental delay with seizures, umbilical hernia and nail hypoplasia as features. [ispub.com]

  Our patient has significant macrocephaly ( 5 SD) and Arnold–Chiari malformation type I. Moreover, the macrocephaly in our patient was progressive, which is a very unusual feature and has not been described before. [nature.com]

  Craniofacial malformations may include an abnormally small head (microcephaly) or large head (macrocephaly); a wide nose with a low nasal bridge; a wide mouth with thick, prominent lips; thick eyebrows and eyelashes or excess hair growth in unusual places [rarediseases.org]

• Small Head

  In addition, people with this condition may have an abnormally small head (microcephaly). [ghr.nlm.nih.gov]

  Craniofacial malformations may include an abnormally small head (microcephaly) or large head (macrocephaly); a wide nose with a low nasal bridge; a wide mouth with thick, prominent lips; thick eyebrows and eyelashes or excess hair growth in unusual places [rarediseases.org]

• Hypertrichosis

  abnormal corpus callosum, intellectual disability, and minor anomalies is caused by mutations in ARID1B. 56 6 Zweier M...Rauch A 28323383 2017 7 De novo SOX11 mutations cause Coffin-Siris syndrome. 61 24 6 Tsurusaki Y...Matsumoto N 24886874 2014 8 Hypertrichosis [malacards.org]

  [from OMIM:135900; 2019.07.19] Coffin-Siris syndrome is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or [flybase.org]

  Frequent features (75% to 90%) include postnatal growth deficiency, microcephaly, wide nasal tip and mouth, prominent lips, eyebrow/eyelash hypertrichosis, and scalp hair hypotrichosis. [jamanetwork.com]

  […] include short stature, failure to thrive, feeding difficulties, microcephaly, ophthalmological manifestations (cataracts, ptosis, strabismus), cardiac anomalies (ventricular septal/atrial septal defects, tetralogy of Fallot, patent ductus arteriosus), hypertrichosis [orpha.net]

  Hypertrichosis was described in 94% of patients. None of the other described patients have hyperinsulinism, PCOS or metabolic syndrome. [nature.com]

• Absent Nails

  nails low birth weight feeding difficulties upon birth frequent respiratory infections during infancy hypotonia joint laxity delayed bone age microcephaly coarse facial features, including wide nose, wide mouth, and thick eyebrows and lashes Causes[edit [en.wikipedia.org]

  The first description of the syndrome was published by Coffin and Siris in 1970; they described 3 girls with mental retardation, absent nails of the fifth fingers and hypoplastic distal phalanges [1]. [ispub.com]

  In addition, affected infants and children may have short fifth fingers ("pinkies") and toes with underdeveloped (hypoplastic) or absent nails; other malformations of the fingers and toes; and eye abnormalities. [rarediseases.org]

• Hyperkeratosis

  Wieczorek D...Wollnik B 23906836 2013 5 Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability. 24 56 6 Hoyer J...Reis A 22405089 2012 6 The HHID syndrome of hypertrichosis, hyperkeratosis [malacards.org]

• Confusion

  Neuropathologic findings. 61 56 DeBassio WA...Knoefel JE 3985811 1985 34 Lapsus--caveat emptor: Coffin-Lowry syndrome vs Coffin-Siris syndrome--an example of confusion compounded. 61 56 Gorlin RJ 7294058 1981 35 The Coffin-Siris syndrome: five new cases [malacards.org]

• Delayed Milestone

  Some of the characteristics of CSS that Julia had include global developmental delays, delayed milestones, intellectual disability, a shortened pinky finger and/or toe nail, and hypotonia (low tone). [chop.edu]

Clinical Testing and Workup If indicated, further examinations and specialized imaging techniques are recommended to establish the extent of the disorder. [rarediseases.org]

• Delayed Bone Age

  bone age microcephaly coarse facial features, including wide nose, wide mouth, and thick eyebrows and lashes Causes[edit] Autosomal dominant inheritance is the most likely, usually by de novo mutation. [en.wikipedia.org]

  In many cases spinal abnormalities have been recognized: spina bifida, scoliosis, kyphosis and delayed bone age. Less frequently, there occur blepharoptosis or macroglossia. [ispub.com]

  In addition, affected infants and children may have hypotonia, abnormally loose joints, delayed bone age (2 to 3 years behind the chronological age), and mild to severe intellectual disability. [rarediseases.org]

(January 2018) Treatment[edit] There is no known cure or standard for treatment. Treatment is based on symptoms and may include physical, occupational and speech therapy and educational services as well. [en.wikipedia.org]

Management and treatment Treatment is essentially supportive and symptomatic. Occupational, physical and speech therapy are recommended. [orpha.net]

Standard Therapies Treatment The treatment of CSS is directed toward the specific features of each individual. [rarediseases.org]

Nasopharyngeal Pneumococcal Vaccine Serotypes and Increase of Nonvaccine Serotypes Among Vaccinated Infants and Their Mothers 5 Years After Introduction of Pneumococcal Conjugate Vaccine 13 in The Gambia. 61 Usuf E...Roca A 30165376 2019 9 [OISO, automatic treatment [malacards.org]

MANAGEMENT AND TREATMENT: At time of diagnosis: - Consultation with a clinical geneticist and/or genetic counselor - Neurologic and/or developmental examination to record developmental milestones and identify neurologic symptoms or deficits - Evaluation [fdna.health]

Prognosis The prognosis is poor in severely affected individuals, with aspiration pneumonia and seizures reported in childhood. Association of tumor development including schwannomatosis has been reported. [orpha.net]

Etiology Heterozygous mutation or genomic rearrangement in the following nine genes have been reported to be causative for CSS (highest to lowest proportion of reported cases): ARID1B (6q25.3), SMARCA4 (19p13.3), SMARCC2 (12q13.2), ARID1A (1p36.11), SOX11 [orpha.net]

Its etiology is unknown, but it is believed to have an autosomal recessive mode of inheritance. Patients with this syndrome are chromosomally normal. The location of the Coffin-Siris gene has tentatively been identified (3–6). [journals.lww.com]

Summary Epidemiology More than 150 cases of genetically confirmed Coffin-Siris syndrome (CSS) have been clinically reported to date. Exact prevalence and incidence are not known but the disorder is probably under-recognized. [orpha.net]

During infancy, treatment may also require measures to help prevent or aggressively treat respiratory infections. Early intervention may be important in ensuring that affected children reach their potential. [rarediseases.org]

La Vista, NE, USA), which stabilizes nucleated blood cells and prevents the release of genomic DNA. cfDNA was isolated using the QIAamp Circulating Nucleic Acid Kit (QIAGEN, Hilden, Germany). [karger.com]