Alagille syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: Arteriohepatic dysplasia
Syndromic bile duct paucity
Alagille-Watson syndrome
Number of Symptoms 42
OrphanetNr: 52
OMIM Id: 118450
610205
ICD-10: Q44.7
UMLs: C0085280
MeSH: D016738
MedDRA: 10053870
Snomed: 31742004

Prevalence, inheritance and age of onset:

Prevalence: 0.4 of 100 000 [Orphanet]
Inheritance: Autosomal dominant
[Orphanet]
Age of onset: All ages
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic biliary tract disease
 -Rare genetic disease
Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare developmental defect during embryogenesis
Polymalformative genetic syndrome with increased risk of developing cancer
 -Rare genetic disease
 -Rare oncologic disease
Rare biliary tract disease
 -Rare hepatic disease
Rare disease with glaucoma as a major feature
 -Rare eye disease
 -Rare genetic disease
Rare syndrome with cardiac malformations
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Syndromic developmental defect of the eye
 -Rare developmental defect during embryogenesis
 -Rare eye disease
 -Rare genetic disease
Syndromic renal or urinary tract malformation
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare renal disease
Syndromic visceral malformation
 -Rare abdominal surgical disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
(HPO:0000100) Nephrotic syndrome Occasional [Orphanet] 83 / 7739
2
(HPO:0000069) Abnormality of the ureter Occasional [Orphanet] 47 / 7739
3
(HPO:0000035) Abnormality of the testis Occasional [Orphanet] 296 / 7739
4
(HPO:0008678) Renal hypoplasia/aplasia Occasional [Orphanet] 127 / 7739
5
(HPO:0000307) Pointed chin Frequent [Orphanet] 45 / 7739
6
(HPO:0000494) Downslanted palpebral fissures Occasional [Orphanet] 328 / 7739
7
(HPO:0000490) Deeply set eye Occasional [Orphanet] 131 / 7739
8
(HPO:0000311) Round face Frequent [Orphanet] 104 / 7739
9
(HPO:0000280) Coarse facial features Frequent [Orphanet] 189 / 7739
10
(HPO:0012368) Flat face Occasional [Orphanet] 106 / 7739
11
(HPO:0002007) Frontal bossing Frequent [Orphanet] 366 / 7739
12
(HPO:0000322) Short philtrum Occasional [Orphanet] 130 / 7739
13
(HPO:0000316) Hypertelorism Occasional [Orphanet] 644 / 7739
14
(HPO:0000248) Brachycephaly Occasional [Orphanet] 222 / 7739
15
(HPO:0005105) Abnormal nasal morphology Frequent [Orphanet] 114 / 7739
16
(HPO:0000277) Abnormality of the mandible Occasional [Orphanet] 394 / 7739
17
(HPO:0000615) Abnormality of the pupil Occasional [Orphanet] 39 / 7739
18
(HPO:0000486) Strabismus Occasional [Orphanet] 576 / 7739
19
(HPO:0100692) Increased corneal curvature Occasional [Orphanet] 13 / 7739
20
(HPO:0001131) Corneal dystrophy Very frequent [Orphanet] 56 / 7739
21
(HPO:0000411) Protruding ear Frequent [Orphanet] 140 / 7739
22
(HPO:0008373) Puberty and gonadal disorders Occasional [Orphanet] 156 / 7739
23
(HPO:0003422) Vertebral segmentation defect Frequent [Orphanet] 95 / 7739
24
(HPO:0002750) Delayed skeletal maturation Occasional [Orphanet] 250 / 7739
25
(HPO:0002997) Abnormality of the ulna Occasional [Orphanet] 75 / 7739
26
(HPO:0000772) Abnormality of the ribs Occasional [Orphanet] 146 / 7739
27
(HPO:0003312) Abnormal form of the vertebral bodies Frequent [Orphanet] 172 / 7739
28
(HPO:0004209) Clinodactyly of the 5th finger Occasional [Orphanet] 288 / 7739
29
(HPO:0009882) Short distal phalanx of finger Occasional [Orphanet] 125 / 7739
30
(HPO:0003298) Spina bifida occulta Frequent [Orphanet] 67 / 7739
31
(HPO:0001396) Cholestasis Very frequent [Orphanet] 136 / 7739
32
(HPO:0005248) Intrahepatic biliary atresia Very frequent [Orphanet] 6 / 7739
33
(HPO:0002240) Hepatomegaly Very frequent [Orphanet] 467 / 7739
34
(HPO:0004325) Decreased body weight Very frequent [Orphanet] 492 / 7739
35
(HPO:0001511) Intrauterine growth retardation Frequent [Orphanet] 358 / 7739
36
(HPO:0100585) Telangiectasia of the skin Frequent [Orphanet] 66 / 7739
37
(HPO:0000822) Hypertension Occasional [Orphanet] 224 / 7739
38
(HPO:0001629) Ventricular septal defect Very frequent [Orphanet] 316 / 7739
39
(HPO:0004414) Abnormality of the pulmonary artery Occasional [Orphanet] 50 / 7739
40
(HPO:0001631) Atria septal defect Occasional [Orphanet] 274 / 7739
41
(HPO:0012758) Neurodevelopmental delay Occasional [Orphanet] 949 / 7739
42
(HPO:0001428) Somatic mutation Occasional [Orphanet] 100 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis GeneReviews The clinical diagnostic criteria for Alagille syndrome (ALGS) include the following:...
Clinical Description GeneReviews Alagille syndrome (ALGS) is a multisystem disorder. Studies of families with multiple affected members and/or JAG1 mutations have demonstrated a wide spectrum of clinical variability ranging from life-threatening liver or cardiac disease to only subclinical manifestations (i.e., butterfly vertebrae, posterior embryotoxon, or characteristic facial features). This variability is seen even among individuals from the same family [Kamath et al 2003]. Indeed, in a study of 53 mutation-positive relatives of affected individuals, 25 (47%) did not meet clinical diagnostic criteria [Kamath et al 2003]....
Genotype-Phenotype Correlations GeneReviews The phenotype of ALGS caused by mutations in JAG1 is indistinguishable from the phenotype caused by mutations in NOTCH2. Initially, 3/3 relatives who had NOTCH2 mutations had significant renal disease, often resulting in end-stage renal disease [McDaniell et al 2006]. More recent studies have shown that renal involvement was noted in 4/9 affected individuals evaluated for renal anomalies. This observation is consistent with the renal involvement observed in those with JAG1 mutations. However, it is important to note that the number of individuals identified with ALGS caused by NOTCH2 mutations is still too small to draw any conclusions about genotype-phenotype correlations [Kamath et al 2012a]....
Differential Diagnosis GeneReviews Table 3. Alagille Syndrome: OMIM Phenotypic Series...
Management GeneReviews To establish the extent of disease and needs in an individual diagnosed with Alagille syndrome (ALGS), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....