A very rare, slowly progressive dysmyelinating disease
affecting, in a diffuse pattern, the cerebrum, cerebellum, brainstem, and
spinal cord. Two types are described: X-linked (infantile form) and the
autosomal dominant (preadulthood form). Clinical features also include
stridor, muscle spasticity, and nystagmus. Often fatal in the first year of
life from respiratory complications.
Perinatal Sudanophilic Leukodystrophy Acute Infantile
form; Connatal Pelizaeus-Merzbacher Syndrome; Seitelberger type of
Described in 1908 by F. Palizaeus, a German neurologist,
and L. Merzbacher, a German psychiatrist.
In the United States and internationally, prevalence is
estimated to be about 1:100,000 to 1:1 million. There are no reports of
African descent published; however, African American cases do exist. Also
present in Asia and Europe.
X-linked recessive (infantile form) affects
boys. Female heterozygotes can be clinically affected. Autosomal dominant
(preadulthood form). Caused by a mutation of PLP on the X chromosome. PLP
encodes two products—PLP and a smaller protein DM20. Approximately 60 to
70% of cases result from duplication of the X chromosome that contains
the PLP protein.
There is a loss of myelin with intact axons
because of an anomaly in the gene for proteolipid protein located on
chromosome X-q22; this makes oligodendrocytes unable to produce myelin.
Severe Pelizaeus-Merzbacher disease is often fatal in the first year of
life, typically from respiratory complications. Patients with classic
Pelizaeus-Merzbacher disease may survive until the sixth decade. Patients
affected with the Spastic Paraplegia type II (SPG II) generally have a
normal life span.
Only men are affected. Diagnosis is based on the
clinical constellation. CT scan and MRI are normal in the early stages, but may
show ventricular enlargement. Evoked potentials are usually normal but may
show delayed latencies.
Group of diseases characterized by progressive
mental retardation and abnormal movements; there are three forms of clinical
Infantile form (fast progression): Also called the connatal Pelizaeus-Merzbacher disease. During the first 2
weeks of life the infant presents with severe head shaking with nystagmus
and roving eye movements. Poor airway tone with stridor and respiratory
complications, severe hypotonia. Motor function is very severely limited.
Choreoathetotic movements and spasticity. Developmental milestones are
delayed. Acquired microcephaly. Optic atrophy and facial weakness develop
later. Seizures are possible. Death usually occurs before 5 to 7 years of
Infantile form (slow progression): The signs of the disease appear later and the evolution is slower. The
nystagmus is weaker but stridor, dystonia, and pyramidal signs are present.
Seizures and cerebellar ataxia are possible. Dysarthria and difficult
swallowing develop later. Acquired microcephaly. These children never walk
and are unable to sit without support. Death usually occurs in the second to
Preadulthood form: Nystagmus may not be present or mild. Limb spasticity that is much worse in
the legs, ataxia that affects speech, hyperreflexia, and Babinski signs are
present. Mild distal sensory loss.