Medical Journal of Dr. D.Y. Patil Vidyapeeth

CASE REPORT
Year
: 2017  |  Volume : 10  |  Issue : 5  |  Page : 473--475

A seizuring alagille syndrome


Jomon Mathew John 
 Department of Paediatrics, Malankara Orthodox Syrian Church Medical College, Kolenchery, Kerala, India

Correspondence Address:
Jomon Mathew John
Karimarathinal, 44/2398, Santhipuram Road, Palarivattom, Ernakulam - 682 025, Kerala
India

Abstract

Alagille syndrome is a rare autosomal dominant inherited disorder with incidence of one in 100,000 live births. This syndrome with seizure as a presentation has been rarely reported in Indian studies. We present a 3-month-old infant who presented to us with seizures was found to have a dysmorphic face, jaundice, hepatomegaly, and soft systolic murmur. Infant was stabilized and remained seizure free. A detailed clinical evaluation of a common presentation may reveal a rare syndrome.



How to cite this article:
John JM. A seizuring alagille syndrome.Med J DY Patil Univ 2017;10:473-475


How to cite this URL:
John JM. A seizuring alagille syndrome. Med J DY Patil Univ [serial online] 2017 [cited 2019 Dec 12 ];10:473-475
Available from: http://www.mjdrdypu.org/text.asp?2017/10/5/473/218180


Full Text



 Introduction



Alagille syndrome (AS) is an autosomal dominant disorder associated with abnormalities of the liver, heart, skeleton, eye, and kidneys and a characteristic facial appearance.[1] In 1973, Watson and Miller reported nine cases of neonatal liver disease with familial pulmonary valvular stenosis. Then in 1975, Alagille et al. described several patients with hypoplasia of the hepatic ducts with associated features.[2]

The incidence rate is approximately one case in every 100,000 live births.

Mutations in either jagged-1 (JAG1) or notch-2 (NOTCH2) have been reported in patients with AS. The syndrome has been mapped to the 20p12-jagged-1 locus, JAG1, which encodes a ligand critical to the notch gene–signaling cascade that is important in fetal development. Notch signaling has been found to regulate the formation of 3-dimensional intrahepatic biliary architecture in murine models.[3],[4]

 Case Report



Three-month-old boy baby born to a primi mother presented with excessive cry and reduced feeding for 2 days and generalized tonic–clonic seizures with uprolling of eyes lasting for 30 min associated with frothing and urinary incontinence. There was no history of fever, head trauma, no family history of seizures, developmentally normal, and immunized for age.

On examination, the child has dysmorphic face with severe pallor and icterus. Anterior fontanelle was bulged and tensed. No neurocutaneous markers. Anthropometric parameters were within the normal limits. There were no focal neurological deficits. The liver was palpable 4 cm below the right costal margin with round border, soft consistency, and smooth surface with total span of 6 cm. Spleen was not palpable. On auscultation, he had a grade 3 ejection systolic murmur over the pulmonary area. Respiratory system was normal.

Course in the hospital

The child was resuscitated and stabilized in casualty, shifted to the Pediatric Intensive Care Unit. The child was electively intubated. Routine investigation and liver function tests were done and showed anemia, conjugated hyperbilirubinemia. Total cholesterol was high.

Computed tomography imaging of the brain showed intraparenchmal hematoma in the left parietal region with midline shift [Figure 1].{Figure 1}

X-ray of the lumbar vertebra was done which showed butterfly vertebrae [Figure 2].{Figure 2}

The ECG shows a right axis deviation with a rsR' pattern [Figure 3]. Subsequently an echocardiography was done which revealed moderate to severe right pulmonary artery stenosis with ostium secundum atrial septal defect.{Figure 3}

With the above features, the diagnosis of AS was made. Packed cell transfusion and intravenous antibiotic were empirically started along with antiepileptic drugs.

Gradually, the child improved on ventilator and was extubated after 10 days. He remained seizure free. He was discharged on vitamin supplementation (A, D, E, K) and syrup ursodecholic acid.

 Discussion



Children with AS often present with poor linear growth.

Commonly associated facial features include broadened forehead, pointed chin, and elongated nose with bulbous tip. Most frequent ophthalmologic finding is a posterior embryotoxon. Some of these patients may also have the Axenfeld anomaly. Other findings reported include retinitis pigmentosa, pupillary abnormalities, and anomalies of the optic disc. The most common cardiac lesions are stenoses within the pulmonary tree (peripheral pulmonic stenosis) with or without other structural lesions. Hemodynamically significant lesions include atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus, and pulmonary atresia. Significant intracardiac lesions place patients with AS at increased mortality risk. Recent data have reported an association between Wolff–Parkinson–White syndrome in a subset of patients with AS.[5]

Vascular lesions include basilar artery aneurysms, internal carotid artery anomalies, middle cerebral artery aneurysm, Moyamoya disease and aortic aneurysms, coarctation of the aorta, and renal artery stenosis.

Abnormalities of the vertebrae, ribs, and hands are frequently associated with AS such as butterfly hemivertebrae and other isolated anomalies include rib anomalies and shortening of the radius, ulna, and phalanges.

As the differential diagnosis of cholestasis is extensive, early recognition is essential to ensure timely treatment and optimal prognosis. Developments in molecular genetic techniques have enabled the identification of causative genes, which has improved diagnostic accuracy for patients.[6],[7]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Krantz ID, Piccoli DA, Spinner NB. Alagille syndrome. J Med Genet 1997;34:152-7.
2Watson GH, Miller V. Arteriohepatic dysplasia: Familial pulmonary arterial stenosis with neonatal liver disease. Arch Dis Child 1973;48:459-66.
3Li L, Krantz ID, Deng Y, Genin A, Banta AB, Collins CC, et al. Alagille syndrome is caused by mutations in human jagged1, which encodes a ligand for notch1. Nat Genet 1997;16:243-51.
4Boyer-Di Ponio J, Wright-Crosnier C, Groyer-Picard MT, Driancourt C, Beau I, Hadchouel M, et al. Biological function of mutant forms of JAGGED1 proteins in Alagille syndrome: Inhibitory effect on notch signaling. Hum Mol Genet 2007;16:2683-92.
5Lalani SR, Thakuria JV, Cox GF, Wang X, Bi W, Bray MS, et al. 20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable neurocognitive deficits. J Med Genet 2009;46:168-75.
6Venigalla S, Gourley GR. Neonatal cholestasis. Semin Perinatol 2004;28:348-55.
7Hartley JL, Gissen P, Kelly DA. Alagille syndrome and other hereditary causes of cholestasis. Clin Liver Dis 2013;17:279-300.