Radiologic, genetic, and endocrine findings in isolated congenital nasal pyriform aperture stenosis patients.

BACKGROUND: Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of upper airway obstruction in neonates. It can occur either associated with a solitary median maxillary central incisor (SMMCI) in 40-75% of cases or as an isolated morphogenic variant. Brain MRI is routinely performed in patients with CNPAS with a SCMMI due to the concomitant risks of intracranial midline defects of the hypothalamic-pituitary axis (HPA), holoprosencephaly, or associated endocrine dysfunction. However, the role of routine brain imaging and endocrinologic evaluation in patients with isolated CNPAS is not frequently studied given the assumption that isolated CNPAS is unlikely to be associated with any intracranial findings.

OBJECTIVES: To evaluate intracranial findings on dual brain MRI imaging in isolated CNPAS patients and to determine if any radiologic, endocrinologic, or genetic abnormalities existed in these patients.

METHODS: We performed a single-institution retrospective review and case series of patients with isolated CNPAS from 2006 to 2019. Findings from dual brain MRI imaging, cytogenetic and karyotype testing, and formal endocrinologic testing were analyzed for each patient and compared to reported findings in isolated CNPAS patients within the literature.

RESULTS: From 2006 to 2019, 16/29 patients were identified at our institution with isolated CNPAS. Inpatient otolaryngologic consultation, CT, and brain MRI imaging was obtained after a mean postnatal age of 3.21 days, 13.5 days, and 35.91 days, respectively. Dual brain MRI imaging was obtained in 12/16 (75%) patients. In our patients, abnormal MRI findings included hypothalamic hamartoma, pars intermedius cyst, and grades 1 and 4 germinal matrix hemorrhages. No holoprosencephaly was found in any patient. Genetic testing was performed on 10/16 (62.5%) patients. Karyotyping was normal in all patients and microarray testing was abnormal in 2/10 patients that represented a 2p16.3 deletion in one patient and a 7q36 deletion causing an unbalanced translocation mutation of the Sonic Hedgehog gene in the second patient. In the latter patient, a hypothalamic hamartoma and panhypopituitarism was found. Endocrine evaluation was performed in 5 patients and was normal in 3/5 patients.

CONCLUSIONS: Our case series of isolated CNPAS patients identified multiple abnormalities on radiologic, genetic, and endocrine testing; one of which that involved a defect of the HPA with panhypopituitarism resulting from a hypothalamic hamartoma. Based upon our findings, dedicated brain MRI imaging, endocrinologic, and genetic testing, should likely be considered for any newly diagnosed, isolated CNPAS patient given the uncommon but potential risk for associated intracranial abnormalities.