Updated 2006-01-18 by Juliana Leite, MD

Original text 1999-05-07 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synonyms: Zellweger syndrome.

Definition:  One of the four syndromes of the “peroxisome biogenesis disorders” resulting from anomalous enzymatic function of the metabolism of fatty acids due to deficient peroxisomes.

Incidence: 0.2–0.25:10,000. There proportion between males and females is 1:1. The probable locus is on the long arm of chromosome 7 in the 21–22 regions.

Etiology: Autosomal recessive with variable expression.

Diagnosis: The fetuses demonstrate growth restriction, hypotonicity with decreased movements and increased nuchal translucency. Abnormal head shape (bulging forehead, wide metopic suture), facial dysmorphism (micrognathia, and buphthalmos), central nervous system anomalies (hydrocephalus, periventricular cysts, ventriculomegaly, hepatomegaly with dysgenesis, cardiac anomalies, clinodactyly and simian creases can also be detected prenatally regions.

Figure 1: Buphophtalmos. Note the enlarged size of the eye.

Genetic anomalies: The probable locus is on the long arm of chromosome 7 in the 21-22 region. A genetic diagnosis can be performed by amniocentesis[4].

Differential diagnosis: Many aneuploidies may present with similar findings. Down syndrome is commonly misdiagnosed, due to the overlapping of several structural findings3.

Prognosis: Most infants die within the first year.

Management: Termination of pregnancy can be offered before viability. Standard prenatal care is not altered when continuation the pregnancy is opted. Confirmation of diagnosis after birth is important for genetic counseling.

Reference:

[1] Nakai A, Shigematsu Y, Nishida K, Kikawa Y, Konishi Y MRI findings of Zellweger syndrome. Pediatr Neurol 1995 Nov;13(4):346-8

[2] Russel IM, van Sonderen L, van Straaten HL, Barth PG:  Subependymal germinolytic cysts in Zellweger syndrome. Pediatr Radiol 1995;25(4):254-5

[3] Jones Kl. Zellweger syndrome in Smith’s recognizable patterns of human malformation. WB Saunders Company – Philadelphia, 1998, 212-213.

[4] Lazarow PB, Small GM, Santos M, Shio H, Moser A, Moser H, Esterman A, Black V, Dancis J: Zellweger syndrome amniocytes: morphological appearance and a simple sedimentation method for prenatal diagnosis. Pediatr Res 1988 Jul;24(1):63-7