The diagnosis of this syndrome
in females is very difficult because the most characteristic features
(cryptorchidism and hypospadia) are not present. Brain and brainstem malformations
may be present. Arthrogryposis is more prominent in the hands. Smith-Lemli-Opitz
syndrome is due to a severe defect in cholesterol biosynthesis. The defective
enzyme is 7-dehydrocholesterol reductase. This defect leads to a high
level of the cholesterol precursor 7-dehydrocholesterol and low cholesterol
levels. The low cholesterol levels lead to abnormalities of mitochondrial
function, hormone synthesis, myelinization and bile
acid and vitamin D metabolism.
Smith-Lemli-Opitz syndrome can be diagnosed prenatally or postnatally
by measuring 7-dehydrocholesterol using chromatographic assay. Most patients
with Smith-Lemli-Opitz syndrome die during the neonatal period. Survivors
are severely mentally retarded. Smith-Lemli-Opitz syndrome is an autosomal
syndrome or cerebrohepatorenal syndrome is characterized by severe hypotonia,
brachycephaly, widely open fontanels and sutures, hepatomegaly, hypospadias
and cryptorchidism in males (Figure 160.1), and clitoral hypertrophy in
females. Patients with Zellweger syndrome have a prominent forehead, flat
occiput, round face, micrognathia, anteverted nares, low-set dysplastic
ears, hypertelorism, puffy eyelids, epicanthal folds, glaucoma, cataracts,
corneal clouding, and Brushfield spots. Hepatomegaly
may not be present at birth but develops during the first month of life.
Arthrogryposis primarily involves distal joints. Bone radiograph may reveal
calcified stippling of the patella and acetabulum. Magnetic resonance
imaging may show: (1) hypomyelination, (2) perisylvian and perirolandic
cortical malformation, and (3) germinolytic cysts.
Zellweger syndrome is associated with increased serum concentrations of
very-long-chain fatty acids in plasma.
Figure 160.1.— [A] Cherry red spot in a patient with GM1-gangliosidosis.
[B] Hepatosplenomegaly in a patient with Zellweger syndrome.