Very rare Palestinian case report of PRUNE1 p.Asp106Asn mutation: a mutation of global developmental delay.

Abstract

Introduction and importance: The PRUNE1 gene (prune exopolyphosphatase 1), situated on chromosome 1q21.3, encodes a protein crucial for early fetal brain development, regulating processes like the polymerization of microtubules, migration of cells, and proliferation. Common features of Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) include progressive microcephaly, hypotonia, spastic quadriparesis, intellectual disability, and abnormal brain magnetic resonance imaging findings.

Case presentation: A 4-month-old male infant, born at 39 weeks and 2 days via Cesarean, prenatal ultrasound findings were positive for ventricular dilation (hydrocephalus). Postnatally, the infant required admission for transient tachypnea of the newborn. Developmental delays and limb stiffness were evident by 2 months of age, prompting neurological evaluation. Examination at 4 months revealed dysmorphic features, including frontal bossing, low-set, malformed ears, and dolichocephaly, alongside axial hypotonia, spasticity, and knee contractures. Genetic testing confirmed a c.316G>A mutation in the PRUNE1 gene, establishing the diagnosis of NMIHBA.

Clinical discussion: PRUNE1-related NMIHBA is a rare neurodevelopmental disorder characterized by profound developmental delays, microcephaly, and variable neurological findings. This case emphasizes the importance of early recognition and genetic testing in infants with suggestive dysmorphic and neurological features. While management remains supportive, early diagnosis aids in family counseling and long-term care planning.

Conclusion: This report describes a rare presentation of NMIHBA in a Palestinian infant with a PRUNE1 gene mutation, contributing to the limited literature on this disorder. Further studies are required to understand the phenotypic spectrum and molecular mechanisms underlying PRUNE1-related disorders.