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LIG4 Syndrome

DNA Ligase IV Deficiency


  • One patient presented with features of Omenn syndrome (see this term). Etiology LIG4 syndrome is caused by mutations in the LIG4 gene (13q22-q34).[orpha.net]
  • Although not present in all, patients may also present with hypothyroidism and type II diabetes and possibly malignancies such as acute T-cell leukemia . [3] [4] The clinical phenotype of LIG4 syndrome closely resembles that of Nijmegen breakage syndrome[en.wikipedia.org]
  • Patients present with immunodeficiency and developmental and growth delay. Term Browser Genes (2) Models (2) Disease References using Mouse Models (2)[informatics.jax.org]
  • Patients present with immunodeficiency and developmental and growth delay. ( 2 ) References: OMIM:606593 Ontology: Human Disease ( DOID:0060021 ) OTHER DNA ligase IV deficiency PAGES GENES INVOLVED Human Gene Zebrafish Ortholog OMIM Term OMIM Phenotype[zfin.org]
  • The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi disease (Fanconi anemia).[humpath.com]
  • Deeg HJ, Socie G, Schoch G, Henry-Amar M, Witherspoon RP, Devergie A, Sullivan KM, Gluckman E, Storb R: Malignancies after marrow transplantation for aplastic anemia and Fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients.[springermedizin.de]
  • Differential diagnosis Differential diagnoses include other rare DNA damage response diseases such as Seckel syndrome, Nijmegen breakage syndrome (NBS), Cernunnos-XLF deficiency and Fanconi anemia (see these terms).[orpha.net]
Short Stature
  • stature syndrome) CDT1 Meier-Gorlin syndrome (Ear-patella-short stature syndrome) ORC1 Meier-Gorlin syndrome (Ear-patella-short stature syndrome) ORC4 Meier-Gorlin syndrome (Ear-patella-short stature syndrome) ORC6 Meier-Gorlin syndrome (Ear-patella-short[genda.com.ar]
  • Abstract We herein describe a case of a 17-year-old boy with intractable common warts, short stature, microcephaly and slowly-progressing pancytopenia.[scinapse.io]
  • RIDDLE syndrome was first described by Stewart et al (2007) in a patient with increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature.[bredagenetics.com]
  • Other features may include pancytopenia, microcephaly, short stature, developmental delay and characteristic facial features. In addition, patients have an increased risk for developing lymphomas and leukemias.[invitae.com]
  • Andrade, Youn Hee Jee and Ola Nilsson , New Genetic Diagnoses of Short Stature Provide Insights into Local Regulation of Childhood Growth , Hormone Research in Paediatrics , 88 , 1 , (22) , (2017) .[doi.org]
  • A plethora of damage response mechanisms collectively act to maintain genomic stability in the face of continuous DNA damage incurred by exogenously and endogenously generated DNA damaging agents.[academic.oup.com]
Epicanthal Folds
  • Table 1 List of reported presenting features in LIG4 patients [ 12 – 18 , 22 – 27 , 31 ] Physical features Microcephaly Growth restriction "Bird-like" or "Seckel syndrome-like" facies Bilateral epicanthic folds Hypogonadism Bone abnormalities Bone Hypoplasia[doi.org]
Skeletal Dysplasia
  • dysplasia, Hydrops-ectopic calcification-moth-eaten skeletal dysplasia, Pelger-Huet anomaly, Reynolds syndrome LIFR Schwartz-Jampel type 2 syndrome, Stuve-Wiedemann dysplasia LMX1B Nail-patella syndrome LRP5 Exudative vitreoretinopathy, Hyperostosis,[genda.com.ar]
  • CENPJ, CEP152, PCNT, ATR, RBBP8, CEP63 Specificity 34 % Genes 100 % Skeletal Dysplasias Core Panel. By Blueprint Genetics in Finland.[mendelian.co]
  • dysplasia 215140 Pelger-Huet anomaly 169400 LEPRE1 1p34.2 Osteogenesis imperfecta, type VIII 610915 LHCGR 2p16.3 Leydig cell adenoma, somatic, with precocious puberty 176410 Leydig cell hypoplasia with hypergonadotropic hypogonadism 238320 Leydig cell[institutobernabeu.com]
Psychomotor Retardation
  • Spinocerebellar ataxia 34133190 EMC1134.610.99Cerebellar atrophy, visual impairment, and psychomotor retardation,616875 EMX2121.810.99Schizencephaly,269160 EP300205.70.990.98Colorectal cancer, somatic,114500 EP300205.70.990.98Rubinstein-Taybi syndrome[qgenomics.com]


  • This study supports the integration of broad unbiased genetic screening into the diagnostic workup of children and young adults with bone marrow failure and myelodysplastic syndromes.[cancerindex.org]


  • Management and treatment Supportive treatment is with prophylactic antibiotics and anti-virals. Hematopoietic stem cell transplantation may be indicated in some patients using modified conditioning regimens without radiotherapy.[orpha.net]
  • Besides this aspect, studies are made in order to discover and develop new treatment strategies to overcome therapy resistance and improve OC survival rates, namely using DNA repair as treatment target.[wjgnet.com]
  • Treatment is mainly supportive, although haematopoietic stem cell transplantation has been used in a few cases.[ncbi.nlm.nih.gov]


  • Prognosis Lifespan is generally limited with an increased incidence of leukemia or lymphoma. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • (PMID: 19147782) Li D … Abbruzzese JL (Clinical cancer research : an official journal of the American Association for Cancer Research 2009) 3 22 44 58 Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining[genecards.org]
  • […] for genotype A /G (p 0.008, OR 0.225, CI 0.075 to 0.680) with added association of genotype A/G with the clinical variables of cytopenia (p 0.032, OR 5.250, CI 1.151 to 23.937), in the range of 0-1 in peripheral blood cytopenias, and with favorable prognosis[bdtd.ibict.br]


  • Etiology LIG4 syndrome is caused by mutations in the LIG4 gene (13q22-q34). The resulting defect of DNA ligase IV, a component of the classical non-homologous end-joining (NHEJ) pathway, affects the major mechanism of DNA double-strand break repair.[orpha.net]
  • […] growth delay unusual facial features microcephaly pancytopenia bone marrow failure ( 17224058 ) skin anomalies Differential diagnosis DNA damage response diseases Nijmegen breakage syndrome (MIM.251260) Seckel syndrome Fanconi disease (Fanconi anemia) Etiology[humpath.com]
  • By the lack of adequate experimental models to the study of this neoplasm, the etiology and the ovarian carcinogenesis still need clarification although some reproductive and hormonal events can be determinant.[wjgnet.com]


  • Summary Epidemiology Prevalence is unknown. To date, at least 12 patients have been reported.[orpha.net]
  • Considerable resources have been invested in epidemiological studies searching for polymorphisms that correlate with cancer predisposition.[academic.oup.com]
  • In this way, there have been made some possible hypothesis, which based on epidemiological and biological observations, pretend to explain susceptibility to OC[ 8 ] (Table 1 ).[wjgnet.com]
Sex distribution
Age distribution


  • Unravelling the pathophysiology has revealed new understandings of the immune system.Areas covered: The description of the clinical phenotype was followed by case descriptions of the immunopathology, description of t... more[scinapse.io]
  • They recapitulate most of the phenotypic features of LIG4 syndrome and may thus serve as a model to explore more in detail the pathophysiology of human LIG4 syndrome. Materials and Methods Generation of Lig4 R/R Mice.[pnas.org]
  • With the wide NF-κB and AP-1 activation thus play important roles in cellular adaptation to environmental changes during pathophysiological states, including hypertension and atherogenesis.[clippingpathtoindia.com]
  • Meningitis, Bacterial A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children.[brenda-enzymes.org]
  • To gain insight into the pathophysiology of RD, we studied the effects of AK2 deficiency using the zebrafish model and induced pluripotent stem cells (iPSCs) derived from fibroblasts of an RD patient.[stanfordchildrens.org]


  • Ubiquitously expressed, it is required to prevent mutagenesis and apoptosis, which can result from DNA double strand breakage caused by intracellular events such as DNA replication and meiosis or extracellular events including damage by reactive oxygen[ncbi.nlm.nih.gov]
  • In other perspective, the definition of a SNP profile could be a useful manner to implement screening and prevention strategies and consequently decrease the OC mortality.[wjgnet.com]
  • Adenoma Polynucleotide kinase 3' phosphatase variant, dietary variables and risk of adenoma recurrence in the Polyp Prevention Trial.[brenda-enzymes.org]
  • This observation suggests that NBS1 helps to prevent alternative NHEJ of signal joints.[kundoc.com]

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