A number sign (#) is used with this entry because this form of Zellweger syndrome (PBD10A) is caused by homozygous mutation in the PEX3 gene (603164) on chromosome 6q24.

Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006).

For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100.

Individuals with PBDs of complementation group 12 (CG12, equivalent to CGG) have mutations in the PEX3 gene. For information on the history of PBD complementation groups, see 214100.

Poulos et al. (1995) described 2 patients who formed a novel peroxisome biogenesis disorder complementation group (group G). Patient 1 was a male infant born to consanguineous Dutch parents. Decreased fetal movement had been noted and the infant was hypotonic at birth. Dysmorphic features included hypertelorism, prominent epicanthic folds, mild micrognathia, and high-arched palate. Ears were box-shaped and slightly low-set. The metopic and sagittal sutures were widely patent; anterior and posterior fontanels were in continuity. Seizures developed on day 1 of life and were controlled with treatment. The condition of the patient deteriorated and he died at 4 months of age. Autopsy showed irregular costochondral ossification in ribs and vertebrae, and marked hypercellularity of marrow preferentially affecting the myeloid series. The cerebrum showed focal microgyria with prominent subcortical ectopic neurons. The inferior olivary nucleus of the medulla was broken into islands with a marked concentration of neurons around the periphery of the nuclei. Patient 2 was the son of consanguineous Italian parents. Fetal movements were poor and the infant was cyanotic at birth, markedly hypotonic, and lacked deep tendon reflexes. He had a prominent midface and downslanting palpebral fissures, hypertelorism, small low-set ears, prominent nose, and high-arched palate. His facies were not considered typical of Zellweger syndrome. There was a slight corneal haze but no cataracts. The liver was enlarged. Echocardiography revealed a right-sided aortic arch, anomalous origin of the right pulmonary artery from the aorta, supravalvular pulmonary stenosis, secundum atrial septal defect, and membranous ventricular septal defect. Seizures developed in the first 20 hours and were controlled by phenobarbital. The infant died at 19 days of age of congestive heart failure. Autopsy showed mild focal microgyria but no obvious subcortical ectopic neurons. Inferior olives were in the form of a broad band, with no obvious concentration of neurons around the periphery. A similarly affected elder sib had died at 15 days of age. Both patients 1 and 2 lacked peroxisomes. Lab values were all abnormal and fell in ranges observed for patients with peroxisome biogenesis disorders.

Muntau et al. (2000) reported 2 unrelated patients with Zellweger syndrome of complementation group G. The patients were male infants from unrelated consanguineous Dutch and Italian families. One showed marked muscular hypotonia at birth. Dysmorphic features included hypertelorism, prominent epicanthic folds, and a high, broad forehead with round face. Seizures developed on day 1 but were controlled with treatment. His condition deteriorated rapidly, with death at age 4 months. The other patient was cyanotic and markedly hypotonic at birth with absent deep tendon reflexes. He had a prominent midface and an antimongoloid slant of the palpebral fissures, ocular hypertelorism, small low-set ears, a prominent nose, and a high-arched palate. The patient died at age 19 days. A brother had been similarly affected and died at age 15 days.

In 2 unrelated patients with Zellweger syndrome of complementation group G, Muntau et al. (2000) identified 2 different homozygous mutations in the PEX3 gene (603164.0001, 603164.0002).