Nasal glial heterotopias, or nasal gliomas, are rare congenital midline lesions composed of ectopic, non-neoplastic glial tissue. They are often mistaken for encephaloceles due to overlapping clinical and embryologic features. Accurate diagnosis is essential to avoid complications associated with surgical intervention. The authors present the case of a newborn female infant born at 35 weeks and 6 days of gestation with a midline nasal mass, respiratory distress, and multiple dysmorphic features. Prenatal and postnatal imaging revealed a pedunculated nasal lesion without intracranial extension and a corpus callosal lipoma suggestive of Pai syndrome. The mass was surgically excised on day of life 2, and tissue was sent for histopathologic evaluation. Pathology confirmed a benign fibroepithelial polyp with rare nerve fibers and negative GFAP staining, consistent with nasal glioma. Postoperatively, the patient exhibited persistent hypotonia, respiratory, and feeding difficulties. Imaging revealed bilateral vestibulocochlear nerve atresia and a hypoplastic facial nerve. Genetic evaluation for Pai syndrome is ongoing. This case highlights the diagnostic and management challenges of nasal gliomas, particularly when associated with syndromic features. MRI is critical for preoperative assessment to exclude intracranial communication. Early surgical excision and multidisciplinary follow-up are essential for optimal outcomes in affected neonates.

Pai syndrome is described as the association of a midline cleft lip, midline facial polyps, and lipoma of the central nervous system. However, only a few patients present the full triad, and most exhibit a wide spectrum of phenotypic variability. Its entire clinical spectrum is still poorly delineated and the etiology remains unknown. In this report, a newborn was presented with congenital nasal septal lipoma, lipoma of the corpus callosum, multiple ventricular septal defect, and additional minor facial dysmorphism. This entity, multiple ventricular septal defect, which has never been reported in PS. Cytogenetic analysis showed normal male 46, XY karyotype. Chromosomal microarray analysis (750 K array) was also unremarkable. This case draws attention with the presence of multiple ventricular septal defect in Pai syndrome and is important in terms of providing phenotypic diversity. To our knowledge, this is also the first genetically evaluated case of Pai syndrome from Turkey.

Lipomas are usually sporadic, asymptomatic lesions, and their clinical and histologic presentation does not pose diagnostic difficulties. In ambiguous cases, however, knowledge of genetics is necessary. HMGA2 expression in adipose cells enables the differentiation of normal adipose tissue from lipoma and liposarcoma. Moreover, lipomas can be associated with genetic diseases, such as multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson's disease, or mitochondrial diseases. Lipomas can run in families (familial multiple lipomatosis) or be a part of genetic syndromes such as PTEN hamartoma tumor syndrome, Proteus syndrome, and Pai syndrome. This study aims to present the genetic basis of lipomas and diseases in which these lesions occur in the clinical picture.

Unique or multiple congenital facial skin polyps are features of several rare syndromes, from the most well-known Pai syndrome (PS), to the less recognized oculoauriculofrontonasal syndrome (OAFNS), encephalocraniocutaneous lipomatosis (ECCL), or Sakoda complex (SC). We set up a research project aiming to identify the molecular bases of PS. We reviewed 27 individuals presenting with a syndromic frontonasal polyp and initially referred for PS. Based on strict clinical classification criteria, we could confirm only nine (33%) typical and two (7%) atypical PS individuals. The remaining ones were either OAFNS (11/27-41%) or presenting with an overlapping syndrome (5/27-19%). Because of the phenotypic overlap between these entities, OAFNS, ECCL, and SC can be either considered as differential diagnosis of PS or part of the same spectrum. Exome and/or genome sequencing from blood DNA in 12 patients and from affected tissue in one patient failed to identify any replication in candidate genes. Taken together, our data suggest that conventional approaches routinely utilized for the identification of molecular etiologies responsible for Mendelian disorders are inconclusive. Future studies on affected tissues and multiomics studies will thus be required in order to address either the contribution of mosaic or noncoding variation in these diseases.

A prenatal and postnatal follow-up of a child with Pai syndrome, especially till toddler age, allows a better understanding of the evolution of this syndrome. This offers insight on possible outcomes especially in what concerns the neurodevelopment.