PMC:4574214 / 14923-17576 JSONTXT

{"project":"2_test","denotations":[{"id":"26376624-22711679-10040325","span":{"begin":474,"end":476},"obj":"22711679"},{"id":"26376624-23815551-10040326","span":{"begin":2144,"end":2146},"obj":"23815551"},{"id":"26376624-23929686-10040327","span":{"begin":2297,"end":2299},"obj":"23929686"}],"text":"Coffin-Siris syndrome and short stature\nRecently, loss of function mutations in ARID1B were identified as causative for Coffin-Siris syndrome, a rare genetic condition characterized by growth deficiency, developmental delay, severe speech impairment, intellectual disability, and specific physical features including microcephaly, coarse facial features, hypertrichosis, hypoplastic or absent fifth fingernails or toenails and hypoplasia or agenesis of the corpus callosum [13]. Our patient A exhibited many features of Coffin-Siris but was not noted to have hypoplastic or absent fifth fingernails or toenails. Our patient B showed typical signs of Coffin-Siris syndrome but not patient C. All three patients exhibited short stature. We performed a comprehensive review on published cases with loss-of-function mutations in ARID1B (Table 1). Based on the available clinical information from the published literature, all patients showed developmental delay (70/70) and language impairment (63/63). Most of patients exhibited hypertonia (49/56), seizures (16/52), agenesis of corpus callosum (23/47), autism or autistic features (9/42) as well as dysmorphic features: low-set or abnormal-shaped ears (42/47), prominent nose (41/55), various eye-related features (51/64), hypertrichosis (38/51), coarse face/abnormal head shape (16/18), low hair line (9/11), and spinal/skeletal anomalies (10/12). Patients ascertained with Coffin-Siris syndrome also exhibited dysplastic nails.\nCase review data showed that 34 % of patients with ARID1B mutations had short stature defined as height below -2 SD. The majority (90 %) had a height Z-score below -1 and none of the patients had above average height. The average Z score among patients for whom height data was available is -1.86. Thus, growth retardation and short stature is a common feature associated with mutations in ARID1B and Coffin-Siris syndrome.\nCoffin-Siris syndrome is a nucleosome remodeling complex (SWI/SNF-SWI) disorder. Mutations in other genes involved with the SWI/SNF complex such as ARID1A, SMARCA2, SMARCA4, SMARCB1 and SMARCE1 are also responsible for Coffin-Siris syndrome [12]. Recent genotype-phenotype analysis indicated that short stature is a prominent feature in patients carrying mutations in those other SWI/SNF genes [14] as well. Among all the Coffin-Siris syndrome patients detected with mutations in those BAF-complex-related-genes (BRG1/brm-associated factor), 21 % of them (9/43) showed short stature. Additionally, 24 % of Coffin-Siris patients without identified mutations presented with short stature. Thus short stature is a common feature of Coffin-Siris syndrome."}