Lig4 syndrome

Qu'est-ce que Lig4 syndrome?

This genetic syndrome is extremely rare with just a few cases reported worldwide, to date.

It presents with a wide range of symptoms including a small head, severe growth and developmental delay and characteristic facial features. Immunodeficiency is also a characteristic feature of the condition.

Syndrome Synonyms:
Lig4 syndrome

Quelles sont les causes du changement de gène Lig4 syndrome?

Elle est causée par des mutations du gène LIG4. Il est hérité selon un schéma autosomique récessif.

L'hérédité autosomique récessive signifie qu'un individu affecté reçoit une copie d'un gène muté de chacun de ses parents, ce qui lui donne deux copies d'un gène muté. Les parents qui ne portent qu'une seule copie de la mutation génique ne présenteront généralement aucun symptôme, mais auront 25% de chances de transmettre les copies des mutations génétiques à chacun de leurs enfants.

Quels sont les principaux symptômes de Lig4 syndrome?

Characteristics facial features of the syndrome include a small head, a beak-like nose and small jaw.

Skin conditions are also common with the syndrome. These might include photosensitivity and skin lesions similar to psoriasis.

Immunodeficiency is also a feature of the syndrome, along with telangiectasias, leukemia, lymphoma, bone marrow abnormalities, and type 2 diabetes.

Possible clinical traits/features:
Thin vermilion border, Cutaneous photosensitivity, Microcephaly, Telangiectasia of the skin, Type II diabetes mellitus, Severe combined immunodeficiency, Telecanthus, Upslanted palpebral fissure, Acute leukemia, Bone marrow hypocellularity, Wide nasal bridge, Abnormality of calvarial morphology, Clinodactyly of the 5th finger, Cryptorchidism, Epicanthus, Hypoplasia of penis, Hypothyroidism, Malabsorption, Hepatomegaly, Cognitive impairment, Leukocytosis, Lymphadenopathy, Lymphoma, Low anterior hairline, Abnormality of chromosome stability, Abnormal nasal morphology, Micrognathia, Narrow forehead

Comment quelqu'un se fait-il tester pour Lig4 syndrome?

Les premiers tests de Lig4 syndrome peut commencer par un dépistage par analyse faciale, en passant par le FDNA Telehealth plateforme de télégénétique, qui permet d'identifier les marqueurs clés de la syndrome et souligner la nécessité de tests supplémentaires. Une consultation avec un conseiller génétique puis un généticien suivra. 

Sur la base de cette consultation clinique avec un généticien, les différentes options pour les tests génétiques seront partagées et le consentement sera recherché pour des tests supplémentaires.

Informations médicales sur Lig4 syndrome

O'Driscoll et al., (2001) reported four patients with immunodeficiency, developmental delay, and poor growth. Two patients were age nine years, and one was 46 and the other 48 years old. There was said to overlap with the features of Nijmegen syndrome. No clinical photographs were published. The facial features were said to be 'Seckel-like' with microcephaly. There were pancytopenia and myelodysplasia in one older patient. The 46-year-old patient had hypothyroidism and type II diabetes. Various skin abnormalities were reported including extensive plantar warts, photosensitivity, psoriasis and erythroderma. Mutations in the DNA ligase IV gene were identified. This functions in DNA nonhomologous end-joining and V(D)J recombination.
A previous patient with a DNA ligase IV mutation had been reported by Riballo et al., (1999). This patient did not have immunodeficiency or any other clinical abnormalities but developed leukaemia at the age of 14 years and dramatically over responded to radiotherapy. The patient reported by Ben-Omran et al., (2005), also showed overlap with Nijmegen breakage syndrome (especially in facial gestalt). He presented with T-cell leukemia. A patient reported by Buck et al., (2005) had SCID.
Eleven patients with mutations and a form of microcephalic primordial dwarfism with extreme postnatal growth were reported by Murray et al., (2014). Most developed thrombocytopenia and leucopenia in childhood. and later immunodeficiency. Note, these authors suggest overlap at least facially, with Dubowitz syndrome. In early childhood, there is fine, sparse hair, epicanthic folds, depressed nasal bridge, broad nasal tip and prominent jaw.
Altmann et al. (2016) reviewed the phenotype of Lig4 syndrome. The most common feature is congenital non-progressive microcephaly (26/28 patients). Severe prenatal growth restriction is common. Abnormal facial features are described as þbird-likeþ or þSeckel syndrome-likeþ (beaked nose, prominent midface, receding forehead, micrognathia). Many patients have epicanthal folds. Skeletal findings include bone hypoplasia, syndactyly, polydactyly and congenital hip dysplasia. Ten patients presented with a variety of skin disorders including photosensitivity, psoriasis, eczema, erythroderma, ecchymosis and hypopigmentation. Three patients have been described with hypogonadism presenting with primary amenorrhea or failing to progress through puberty. Neurodevelopmental delay is frequently (but not universally) present. Immunological abnormalities include combined immunodeficiency with profound T- and B-lymphocytopenia and varying degrees of hypogammaglobulinaemia, often associated with a raised IgM. There is increased susceptibility to bacterial, viral and fungal infection leading to multiple hospital admissions and failure to thrive. A severe combined immunodeficiency (SCID), has been described in four patients. One patient had features of Omenn's syndrome. Autoimmunity was described in one patient. Six LIG4 patients had malignancy including lymphoma and squamous cell carcinoma.
Dard et al. (2016) described two unrelated patients with Lig4 syndrome. Both individuals had dysmorphic features including triangular-shaped face, large eyes, downward slanting palpebral fissures, thin palpebral fissures, elongated ears, prominent nose with low set columella and hypoplasic alae nasi, micrognathia, mild retrognathia, short philtrum and narrow forehead. Additional features included bushy hair, deep palmar creases, short IV toe with brachymetatarsy, partial 2-3 syndactyly of the toes, and multiple warts on the limbs. Developmental delay of variable degree was present. The affected individuals had recurrent infections, low immunoglobulin levels and slowly progressive pancytopenia. The authors suggested that immunoglobulin class deficiency (IgM or IgA) was dependant on the genotype.
Walne et al. (2016) reported on patients presenting with features of dyskeratosis congenita but negative for mutations in the classical dyskeratosis congenita genes. Biallelic variants were identified in 17 individuals from 12 families, 4 of them consanguineous. These were homozygous variants (frameshift or missense) in USB1 (eight families), homozygous variants (missense) in GRHL2 (two families) and identical compound heterozygous variants (frameshift) in LIG4 (two families). All patients had features of dyskeratosis congenita but not the characteristic short telomeres. The common clinical features (>60% cases) were nail dystrophy, abnormal skin pigmentation and bone marrow failure. Additional features, present in some patients, included leukoplakia, developmental delay, microcephaly, growth restriction, hair loss, pulmonary disease, cancer, abnormal dentition, gonadal abnormalities, ear abnormalities including abnormal hearing, eye abnormalities, abnormal facies, skeletal abnormalities and immune deficiency.

* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

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Parents de Lillie

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