OMIM ID:
Pelizeaus-Merzbacher Disease
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Nystagmus is the major ocular feature in this disease and may appear as early as the first weeks of life in severe cases. However, more mildly affected individuals may never have nystagmus and, further, it can disappear later. The ocular movements are usually pendular but may have horizontal and rotatory components as well. The presence of nystagmus is diagnostically important as it is an uncommon finding in other leukodystrophies.
Systemic Features
The classic disease is infantile in onset with hypotonia, titubation, weakness, stridor, respiratory problems, and even seizures often noted in the first weeks of life. Ataxia, spasticity and cognitive delay are soon apparent. Infants affected early and severely may never achieve normal motor or mental milestones whereas those less severely affected may at some point ambulate and acquire some language skills. However, acquired skills may be lost by adolescence. Survival to the sixth decade of life is common but those with the most severe form of disease may not live beyond the second decade.
This is an X-linked recessive disorder in which only males have the complete syndrome. However, multiple carrier females have been studied and many have subtle evidence of disease mainly in gait and motor control.
Genetics
Inheritance
Pelizeaus-Merzbacher disease is the result of mutations in an X-linked gene PLP1 (Xq22). It is inherited in an X-linked recessive pattern. Duplication of the PLP1 gene is more common than point mutations. The signs and symptoms are not diagnostic of PMD as mutations in other genes can cause a similar phenotype.
Spastic paraplegia-2 (SPG2; 312920)is an allelic disorder in which nystagmus and optic atrophy are also found in some patients.
Pedigree
X-linked recessive, carrier mother
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked recessive, father affected
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.