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.

Keywords: NMIHBA; PRUNE1 gene; Palestine; case report; neurodevelopmental disorder.

Figure 1.

Photographs of the patient reveal subtle dysmorphic characteristics, including frontal bossing, a low-set malformed ear, and dolichocephaly.

Figure 2.

Brain MRI was done at the age of 4 months. A and B (T1-weighted) show an axial view of the brain with mild generalized volume loss and diffuse cortical thinning. Also, there is a slight lag in myelination and peri-cerebral effusion in red arrows. C and D (T2-weighted) showing an axial view of the brain also show diffuse cortical atrophy with wide brain operculum in the red arrow. E (T1-weighted) showing a sagittal view of the brain with thinning of the corpus callosum in red arrow.

Figure 3.

CXR of the patient showed hypo-inflated lungs with no other significant findings.