{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:15:49Z","timestamp":1773803749591,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2021C03094"],"award-info":[{"award-number":["2021C03094"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81371215"],"award-info":[{"award-number":["81371215"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670786"],"award-info":[{"award-number":["81670786"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Kenny\u2013Caffey syndrome type 2 (KCS2) is an extremely rare inherited disorder characterized by proportionate short stature, skeletal defects, ocular and dental abnormalities, and transient hypocalcemia. It is caused by variants in <jats:italic>FAM111A<\/jats:italic> gene. Diagnosis of KCS2 can be challenging because of its similarities to other syndromes, the absence of clear hallmarks and the deficient number of genetically confirmed cases. Here, we aimed to further delineate and summarize the genotype and phenotype of KCS2, in order to get a better understanding of this rare disorder, and promote early diagnosis and intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We present clinical and genetic characteristics of eight newly affected individuals with KCS2 from six families, including one family with three individuals found to be a father\u2010to\u2010daughter transmission, adding to the limited literature<jats:italic>.<\/jats:italic> Furthermore, we performed a review of genetically confirmed KCS2 cases in PubMed, MEDLINE and CNKI databases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were six females and two males in our cohort. All the patients presented with short stature (100.0%). Clinical manifestations included ocular defects such as hypermetropia (5\/8), dental problems such as defective dentition (3\/8) and dental caries (3\/8), skeletal and brain anomalies such as delayed closure of anterior fontanelle (6\/8), cerebral calcification (3\/8), cortical thickening (3\/8) and medullary stenosis (4\/8) of tubular bones. Endocrinologic abnormalities included hypoparathyroidism (5\/8) and hypocalcemia (3\/8). One male patient had micropenis and microorchidism. All cases harboured missense variants of <jats:italic>FAM111A<\/jats:italic>, and nucleotides c.1706 arose as a mutational hotspot, with seven individuals harbouring a c.1706G&gt;A (p.Arg569His) variant, and one child harbouring a c.1531T&gt;C (p.Tyr511His) variant. Literature review yielded a total of 46 patients from 20 papers. Data analysis showed that short stature, hypoparathyroidism and hypocalcemia, ocular and dental defects, skeletal features including cortical thickening and medullary stenosis of tubular bones, and seizures\/spasms were present in more than 70% of the reported KCS2 cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We provide detailed characteristics of the largest KCS2 group in China and present the first genetically confirmed instance of father\u2010to\u2010daughter transmission of KCS2. Our study confirms that Arg569His is the hot spot variant and summarizes the typical phenotypes of KCS2, which would help early diagnosis and intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2433","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T08:30:21Z","timestamp":1712651421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Further delineation of phenotype and genotype of Kenny\u2013Caffey syndrome type 2 (phenotype and genotype of KCS type 2)"],"prefix":"10.1002","volume":"12","author":[{"given":"Xuefei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Children's Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4667-3636","authenticated-orcid":false,"given":"Chaochun","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Children's Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13633-016-0041-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.100.1.1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61896"},{"key":"e_1_2_9_5_1","volume-title":"GeneReviews(\u00ae) University of Washington, Seattle Copyright \u00a9 1993\u20132024, University of Washington, Seattle. 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