butterfly vertebrae

Potter Disease, Type I

Clinical Characteristics
Ocular Features: 

As part of the facial morphology said to be characteristic of Potter disease, there is usually hypertelorism, telecanthus and epicanthal folds.  Cataracts and angiomas of the optic disc area have also been described.

Systemic Features: 

Polycystic kidney disease and hepatic system anomalies are major features of Potter disease.   Pulmonary hypoplasia with neonatal respiratory distress, however, is often the most immediate cause of death in most infants.  Antenatal oligohydramnios and low birth weight are commonly present.  As many as 33% of fetuses die in utero, often the result of bilateral renal agenesis.  Infants that survive can have chronic lung disease and renal dysfunction.  Congenital heart malformations are common, including septal defects, tetralogy of Fallot and patent ductus arteriosis.  Vertebrae may have a ‘butterfly’ shape but other skeletal findings include hemivertebrae and sacral agenesis.  The neck has been described as short and the skull is brachycephalic.

The facial appearance, known as Potter facies, is said to be characteristic and may be helpful in distinguishing this type of polycystic kidney disease.  In addition to the ocular findings, the nares are often anteverted, and the external ears are large and often posteriorly rotated.

Genetics

The uniqueness of this syndrome remains to be established.  There are several polycystic kidney disorders which have a monogenic basis. These often have overlapping renal features with the condition described here but lack the facial features said to be characteristic of Potter type I disease.  Autosomal recessive inheritance has been suggested on the basis of several reported families with affected sibs from consanguineous parents but so far no gene locus or mutation has been identified.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no treatment for the condition but symptoms of respiratory distress and renal failure may need to be addressed acutely.  Long-term therapy for pulmonary disease and renal dysfunction can be considered for older individuals.  Many infants die in the neonatal period.

References
Article Title: 

Syndrome of autosomal recessive polycystic kidneys with skeletal and facial anomalies is not linked to the ARPKD gene locus on chromosome 6p

Hallermann C, M?ocher G, Kohlschmidt N, Wellek B, Schumacher R, Bahlmann F, Shahidi-Asl P, Theile U, Rudnik-Schoneborn S, M?ontefering H, Zerres K. Syndrome of autosomal recessive polycystic kidneys with skeletal and facial anomalies is not linked to the ARPKD gene locus on chromosome 6p. Am J Med Genet. 2000 Jan 17;90(2):115-9. Review.

PubMed ID: 
10607948

Alagille Syndrome

Clinical Characteristics
Ocular Features: 

The ocular findings in Alagille syndrome are often of little functional significance but can be sufficient to suggest the diagnosis without further study of the systemic features.  Posterior embryotoxon is found in 95% of individuals while iris abnormalities such as ectopic pupils are seen in 45%, abnormal fundus pigmentation is common (hypopigmentation in 57%, diffuse pigment speckling in 33%), and optic disc anomalies have been reported in 76%.  One study found that 90% of individuals have optic disk drusen by ultrasonography.  The anterior chamber anomalies are considered by some to be characteristic of Axenfeld anomaly.  The presence of these ocular findings in children with cholestasis should suggest Alagille syndrome.  Ocular examination of the parents can also be helpful in this autosomal dominant disorder as some of the same changes are present in one parent in more than a third of cases.

Systemic Features: 

A variety of  systemic features, some of them serious malformations, occur in Alagille syndrome.  Among the most common is a partial intrahepatic biliary atresia leading to cholestasis and jaundice.  Skeletal malformations include 'butterfly' vertebrae, shortened digits, short stature, a broad forehead, and a pointed chin.  The tip of the nose may appear bulbous.  These features have suggested to some that there is a characteristic facial dysmorphology.  Vascular malformations are common including aneurysms affecting major vessels, valvular insufficiency, coarctation of the aorta, and stenosis and these are often responsible for the most serious health problems.  In fact, vascular events have been reported to be responsible for mortality in 34% of one cohort.  Chronic renal insufficiency develops in a minority of patients.  This disorder should always be considered in children with cholestasis, especially when accompanied by cystic kidney disease.  Brain MRIs may show diffuse or focal hyperintensity of white matter even in the absence of hepatic encephalopathy.

Genetics

This is an autosomal dominant condition secondary to various mutations in the JAG1 gene located on chromosome 20 (20p12).  Penetrance is nearly 100% but there is considerable variation in expression.  A far less common variant of this disorder, ALGS2 (610205), is caused by a mutation in the NOTCH2 gene (1p13-p11).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No cure is available but individual organ disease may be treatable.  The ocular abnormalities generally do not cause vision difficulties.

Reversible of white matter changes has been noted in a single child following liver transplantation.

 

References
Article Title: 

CT-defined phenotype of pulmonary artery

Rodriguez RM, Feinstein JA, Chan FP. CT-defined phenotype of pulmonary artery
stenoses in Alagille syndrome
. Pediatr Radiol. 2016 Apr 4. [Epub ahead of print].

PubMed ID: 
27041277

Alagille syndrome: clinical and ocular pathognomonic features

El-Koofy NM, El-Mahdy R, Fahmy ME, El-Hennawy A, Farag MY, El-Karaksy HM. Alagille syndrome: clinical and ocular pathognomonic features. Eur J Ophthalmol. 2010 Jul 28. pii: 192165A5-8631-4C06-9C47-9AD63688B02A. [Epub ahead of print]

PubMed ID: 
20677167

Ocular abnormalities in Alagille syndrome

Hingorani M, Nischal KK, Davies A, Bentley C, Vivian A, Baker AJ, Mieli-Vergani G, Bird AC, Aclimandos WA. Ocular abnormalities in Alagille syndrome. Ophthalmology. 1999 Feb;106(2):330-7.

PubMed ID: 
9951486
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