Severe Hypotonia, Nystagmus and Hypomyelination in A 9-Month Female Infant: Diagnosing Pelizaeus–Merzbacher Disease Outside the Usual Inheritance Patterns

Abstract

Pelizaeus-Merzbacher disease is a rare X-linked recessive disorder regarding the defective myelin sheath formation in the CNS neurons due to mutations of the proteolipid protein 1 gene (PLP1). Even though it is predominant in males, affected females have been found to represent a small proportion in the medical literature 1. A wide variety of PLP1 mutations have been reported as a cause. Herein, we describe the case of a 9-month-old female with (bearing) the typical features of the disease who was found to have a rare mutation.

Rare Case of Female with Pelizaeus Mertzbacher Disease Due to Deletion of Proteolipid Protein 1

“…PLP1 mutation can be due to point mutation, duplication, or deletion. [1][2][3] PLP1 mutation leads to hypomyelination leading to reduced neurological function. As an X-linked disease, PMD is often seen in males and rarely observed in females.…”

“…For a female patient to be affected, X-linked recessive inheritance pattern by gene mutation and skewed X inactivation needs to take place. 1,2 Patient's mother most likely then has the affected X-linked gene which patient obtained it in an X-linked recessive inheritance with a skewed X inactivation. A review of literature indicates that there are currently at least 13 other cases of affected females with a genetic diagnosis of PMD.…”

“…A review of literature indicates that there are currently at least 13 other cases of affected females with a genetic diagnosis of PMD. [1][2][3][4] Out of the thirteen cases examined, our patient is the second only known female with deletions of PLP1 gene. 1 Twelve other female cases were due to point mutations or duplications of the PLP1 gene.…”

“…1 Twelve other female cases were due to point mutations or duplications of the PLP1 gene. [1][2][3][4] In addition, the second highlight of our case is the importance of performing genetic testing and/ or radiological imaging early on for a patient with developmental delay. Our patient was diagnosed with PMD at 3 years old due to genetic testing.…”

“…1 Patients exhibit signs that progressively worsen for instance nystagmus, hypotonia, ataxia, convulsions, muscle contractions, language delay. 2,3 PMD affects males more than females. There are very few reported cases where females are affected, but our case is the second only reported female patient with PMD due to a deletion of PLP1 gene.…”