LIG4 syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: DNA ligase IV deficiency
Ligase 4 syndrome
Number of Symptoms 33
OrphanetNr: 99812
OMIM Id: 606593
ICD-10: D81.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Combined T and B cell immunodeficiency
 -Rare genetic disease
 -Rare immune disease
Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare genetic disease
Polymalformative genetic syndrome with increased risk of developing cancer
 -Rare genetic disease
 -Rare oncologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000054) Micropenis Occasional [Orphanet] 257 / 7739
2
 (HPO:0000035) Abnormality of the testis Occasional [Orphanet] 296 / 7739
3
 (HPO:0005105) Abnormal nasal morphology Frequent [Orphanet] 114 / 7739
4
 (HPO:0000506) Telecanthus Frequent [Orphanet] 156 / 7739
5
 (HPO:0000248) Brachycephaly Frequent [Orphanet] 222 / 7739
6
 (HPO:0000277) Abnormality of the mandible Frequent [Orphanet] 394 / 7739
7
 (HPO:0000233) Thin vermilion border Frequent [Orphanet] 124 / 7739
8
 (HPO:0000341) Narrow forehead Frequent [Orphanet] 96 / 7739
9
 (HPO:0000286) Epicanthus Frequent [Orphanet] 371 / 7739
10
 (HPO:0000431) Wide nasal bridge Frequent [Orphanet] 290 / 7739
11
 (HPO:0000294) Low anterior hairline Frequent [Orphanet] 52 / 7739
12
 (HPO:0000252) Microcephaly Very frequent [Orphanet] 832 / 7739
13
 (HPO:0000582) Upslanted palpebral fissure Frequent [Orphanet] 185 / 7739
14
 (HPO:0005978) Type II diabetes mellitus Occasional [Orphanet] 68 / 7739
15
 (HPO:0000821) Hypothyroidism Occasional [Orphanet] 141 / 7739
16
 (HPO:0004209) Clinodactyly of the 5th finger Occasional [Orphanet] 288 / 7739
17
 (HPO:0000924) Abnormality of the skeletal system Occasional [Orphanet] 114 / 7739
18
 (HPO:0002024) Malabsorption Occasional [Orphanet] 142 / 7739
19
 (HPO:0002240) Hepatomegaly Occasional [Orphanet] 467 / 7739
20
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 492 / 7739
21
 (HPO:0000992) Cutaneous photosensitivity Frequent [Orphanet] 75 / 7739
22
 (HPO:0010783) Erythema Frequent [Orphanet] 138 / 7739
23
 (HPO:0000951) Abnormality of the skin Frequent [Orphanet] 147 / 7739
24
 (HPO:0100585) Telangiectasia of the skin Occasional [Orphanet] 66 / 7739
25
 (HPO:0002488) Acute leukemia Frequent [Orphanet] 29 / 7739
26
 (HPO:0001876) Pancytopenia Frequent [Orphanet] 89 / 7739
27
 (HPO:0001974) Leukocytosis Occasional [Orphanet] 33 / 7739
28
 (HPO:0002665) Lymphoma Frequent [Orphanet] 60 / 7739
29
 (HPO:0003220) Abnormality of chromosome stability Very frequent [Orphanet] 98 / 7739
30
 (HPO:0004430) Severe combined immunodeficiency Occasional [Orphanet] 16 / 7739
31
 (HPO:0002716) Lymphadenopathy Occasional [Orphanet] 129 / 7739
32
 (HPO:0010978) Abnormality of immune system physiology Very frequent [Orphanet] 148 / 7739
33
 (HPO:0012758) Neurodevelopmental delay Frequent [Orphanet] 949 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM O'Driscoll et al. (2001) identified 4 patients with features including immunodeficiency and developmental and growth delay who had mutations in the LIG4 gene (601837.0001-601837.0004). The clinical phenotype, which they called LIG4 syndrome, closely resembled the DNA damage response ...
Molecular genetics OMIM Girard et al. (2004) showed that the clinical severity among 5 patients with LIG4 syndrome correlated with the level of residual ligase activity. Two linked polymorphisms (A3V, 601837.0005; T9I, 601837.0006) were found to decrease the activity of DNA ...