Extreme Growth Failure is a Common Presentation of Ligase IV Deficiency
نویسندگان
چکیده
Ligase IV syndrome is a rare differential diagnosis for Nijmegen breakage syndrome owing to a shared predisposition to lympho-reticular malignancies, significant microcephaly, and radiation hypersensitivity. Only 16 cases with mutations in LIG4 have been described to date with phenotypes varying from malignancy in developmentally normal individuals, to severe combined immunodeficiency and early mortality. Here, we report the identification of biallelic truncating LIG4 mutations in 11 patients with microcephalic primordial dwarfism presenting with restricted prenatal growth and extreme postnatal global growth failure (average OFC -10.1 s.d., height -5.1 s.d.). Subsequently, most patients developed thrombocytopenia and leucopenia later in childhood and many were found to have previously unrecognized immunodeficiency following molecular diagnosis. None have yet developed malignancy, though all patients tested had cellular radiosensitivity. A genotype-phenotype correlation was also noted with position of truncating mutations corresponding to disease severity. This work extends the phenotypic spectrum associated with LIG4 mutations, establishing that extreme growth retardation with microcephaly is a common presentation of bilallelic truncating mutations. Such growth failure is therefore sufficient to consider a diagnosis of LIG4 deficiency and early recognition of such cases is important as bone marrow failure, immunodeficiency, and sometimes malignancy are long term sequelae of this disorder.
منابع مشابه
Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure
BACKGROUND DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4). The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the clinical diagnosis is often delayed and established by exclusion. METHODS We describe...
متن کاملEXPERIENCE WITH 115 PATIENTS WITH CONGENITAL A DREN AL HYPERPLASIA AND EVALUATION OF GROWTH PATTERNS IN 24 PATIENTS WITH THE SALT-LOSING TYPE
In this study the data on 115 cases of congenital adrenal hyperplasia (CAH) who were followed in the Pediatric Endocrine Clinic at Nemazee Hospital, Shiraz will be reported. Among these cases 51 were male and 64 female. The most common type of CAH in these patients was the salt-losing type of 21 -hydroxylase deficiency (85 .2%). ll-hydroxylase deficiency was present in 13.04% of patients. ...
متن کاملDNA ligase IV syndrome; a review
DNA ligase IV deficiency is a rare primary immunodeficiency, LIG4 syndrome, often associated with other systemic features. DNA ligase IV is part of the non-homologous end joining mechanism, required to repair DNA double stranded breaks. Ubiquitously expressed, it is required to prevent mutagenesis and apoptosis, which can result from DNA double strand breakage caused by intracellular events suc...
متن کاملClinical Protests Food Allergy in Children
The best recognized intestinal manifestation of food allergy is food allergic (food-sensitive) enteropathy. The feature of enteropathy may include lymphocyte and plasma cell infiltration, epithelial abnormality, or crypt hyperplastic villous atrophy, and impairing absorption, enterophaty continues while the food remains in the diet, remitting on an exclusion diet, and usually recurring on food ...
متن کاملA Case of Probable MHC Class II Deficiency with Disseminated BCGitis
Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency disease characterized by abnormality of MHC class II molecules surface expression on peripheral blood lymphocytes and monocytes. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections but the immunodeficiency is not as severe as SCID (severe combined immunodeficien...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 35 شماره
صفحات -
تاریخ انتشار 2014