Ugrás a tartalomhoz
Használja fel HSA- vagy FSA-keretét

Betegségjelentés · Gastrointestinal

Alagille Syndrome

Whole genome sequencing evaluates both JAG1 and NOTCH2 (including the large deletions that account for 7% of JAG1 cases) providing the molecular diagnosis that standard sequencing-only panels may miss.

A betegségjelentés olyan ritka variánsokat keres, amelyekről ismert, hogy okozzák az általa lefedett betegségeket.

Minden készlethez mellékelve

449 $-tólIngyenes szállítás · Eredmények 6–8 hét alatt

Kérem a Genome Testemet

A(z) condition ismertetése

A rare genetic disorder characterized by defects in multiple organ systems, including the liver (often due to bile duct paucity), heart, eyes, and skeleton.

Alagille syndrome (ALGS) is an autosomal dominant multisystem disorder caused by pathogenic variants in JAG1 (~97% of cases, chromosome 20p12.2) or NOTCH2 (~2-3%, chromosome 1p12). JAG1 encodes a ligand in the Notch signaling pathway, which is critical for cell fate determination during embryonic development of bile ducts, heart, vasculature, skeleton, and eyes. Over 600 different JAG1 pathogenic variants have been reported, including missense, nonsense, frameshift, splice site variants, and whole-gene or multi-exon deletions (~7% of cases). ALGS affects approximately 1 in 30,000-50,000 births.

The cardinal features are bile duct paucity (intrahepatic cholestasis with severe pruritus, jaundice, and xanthomas), congenital heart defects (peripheral pulmonic stenosis in ~90%, complex cardiac defects in ~15%), butterfly vertebrae on spine radiographs, posterior embryotoxon on ophthalmological exam, and a characteristic facial appearance (prominent forehead, pointed chin, deep-set eyes). Clinical severity is highly variable, even within the same family carrying the identical JAG1 variant, ranging from subclinical liver involvement to liver failure requiring transplantation in approximately 15-20% of patients.

Maralixibat (Livmarli), an ileal bile acid transporter (IBAT) inhibitor, was approved by the FDA in 2021 for the treatment of cholestatic pruritus in Alagille syndrome patients aged 1 year and older. It reduces serum bile acid levels and significantly improves the debilitating pruritus that impairs quality of life. Odevixibat (Bylvay) is approved for progressive familial intrahepatic cholestasis (PFIC) and is under investigation for ALGS. Liver transplantation remains necessary for patients with progressive liver failure or intractable pruritus despite medical therapy.

Approximately 50-70% of ALGS cases are de novo; parents are unaffected. However, because of variable expressivity, apparently unaffected parents should be evaluated for subtle features (posterior embryotoxon, butterfly vertebrae) before concluding de novo status.

A vizsgált betegség

Autoszomális domináns

Alagille (AGS) syndrome is variably characterized by chronic cholestasis due to paucity of intrahepatic bile ducts, peripheral pulmonary artery stenosis, vertebrae segmentation anomalies, characteristic facies, posterior embryotoxon/anterior segment abnormalities, pigmentary retinopathy, and dysplastic kidneys.

Mit változtat a diagnózis

Maralixibat (Livmarli, FDA 2021) for cholestatic pruritus; ursodeoxycholic acid; fat-soluble vitamin supplementation; liver transplantation for progressive liver failure; cardiac surgery for complex heart defects

Vizsgált gének

Más néven

Alagille-Watson syndrome; Arteriohepatic dysplasia; Cardiovertebral syndrome; hepatic ductular hypoplasia; Hepatofacioneurocardiovertebral syndrome; paucity of interlobular bile ducts; syndromic bile duct paucity; Watson-Miller syndrome

3 kapcsolódó altípust tartalmaz ↓
  • Alagille syndrome due to 20p12 microdeletion
  • Alagille syndrome due to a JAG1 point mutation
  • Alagille syndrome due to a NOTCH2 point mutation
MONDO:0007318Orphanet 52MedGen 39014

Miért a teljes genom szekvenálás

JAG1 whole-gene deletions account for 7% of Alagille syndrome and are missed by exon-sequencing panels. Whole genome sequencing detects both sequence variants and structural rearrangements in a single test.

7% of JAG1 pathogenic alleles are whole-gene or multi-exon deletions invisible to standard sequencing

Approximately 7% of Alagille syndrome patients carry large JAG1 deletions, ranging from single-exon to whole-gene deletions and occasionally extending into flanking genes. Standard Sanger sequencing or exon-only NGS panels do not detect copy number changes, returning a false-negative result in these patients. When a patient meets clinical criteria for ALGS but sequencing of JAG1 is negative, MLPA or chromosomal microarray must be ordered separately. Whole genome sequencing detects both sequence variants and copy number variants from the same data, eliminating this diagnostic gap and the associated time delay.

Molecular diagnosis enables cardiac surveillance planning: 15% of ALGS patients have complex heart defects requiring intervention

While peripheral pulmonic stenosis (present in ~90% of ALGS patients) is generally benign and often resolves with growth, approximately 15% of ALGS patients have complex congenital heart defects (tetralogy of Fallot, pulmonary atresia, ventricular septal defects) requiring surgical intervention. Cardiac evaluation is standard of care for all newly diagnosed ALGS patients. Molecular confirmation in an infant presenting with neonatal cholestasis triggers complete cardiac workup before the heart defect presents clinically. Without molecular diagnosis, cholestatic infants may be evaluated solely for biliary disease, missing concurrent cardiac pathology.

További gastrointestinal conditions

Minden feltétel →

Egy teszt. Egy életen át tartó válaszok.

Egy csomag, házhoz szállítva. Az egész genomját a diagnosztikai döntésekhez használt klinikai színvonalon szekvenáljuk. Orvos számára is használható jelentéseit 6–8 héten belül küldjük el a Genome Manager-be. Ezek tartósan érvényesek, és a tudomány fejlődésével frissülnek.

449 $-tól

Ingyenes szállítás · Eredmények 6–8 hét alatt

Kérem a Genome Testemet