Interstitial 1q Deletion Syndrome: A New Patient with Congenital Diaphragmatic Hernia and Multiple Midline Anomalies

Background: Congenital diaphragmatic hernia (CDH) represents one of the most critical neonatal emergencies, whose timely recognition and appropriate management are essential to ensure patient survival. Genetic investigations play a crucial role for accurate diagnostic assessment, especially in those cases associated with other congenital defects and/or dysmorphic features. Interstitial deletions of chromosome 1q are rare, with about 30 cases reported in the literature. The phenotypical features of the affected subjects described so far include microcephaly, pre- and postnatal growth retardation, psychomotor delay, ear anomalies, brachydactyly, in addition to small hands and feet and rarely congenital diaphragmatic hernia (CDH). Here, we report on a neonate with CDH, dysmorphic features, and multiple midline anomalies, in whom array-comparative genomic hybridization (a-CGH) analysis allowed the identification of an interstitial deletion of the long arm of chromosome 1. Case presentation: The proband is a male infant, born late preterm at 36+1 weeks, with prenatal diagnosis of congenital diaphragmatic hernia (CDH) for which parents refused further genetic investigations. At birth physical examination revealed dysmorphic features and multiple midline anomalies, including cleft palate, pectus excavatum, and ostium primum type atrial septal defect, in addition to hypotonia. Cranial ultrasound showed poor gyral development. a-CGH identified a deletion of approximately 12 Mb on the long arm of chromosome 1, within the region 1q31.1-q32.1, thereafter documented as de novo. On the fourth day of life, he underwent surgical correction of CDH. At about one month of age, the infant was discharged and enrolled in a multidisciplinary follow-up, during which an impaired growth has been evidenced. During the last neuropsychiatric evaluation at the age of 8 months, the child showed mild hypotonia and immature manual exploration. Head control was present but inconsistent. Trunk control was not yet developed, and lower limb positioning exhibited flexion, external rotation and varus attitude of feet. He does not show any further clinical anomalies, and laboratory tests as well as US multiorgan and neurosensorial evaluations do not put in evidence other abnormalities to date. The surgical correction of cleft palate is currently planned to be performed at one year of age. Conclusions: The few cases of chromosome 1q deletions reported to date, along with the clinical and genetic profile of the present neonate, point out that 1q deletions should be considered within the context of "interstitial 1q deletion syndrome". Comparing our case with those described in previous studies, the involved genomic regions and the phenotypic traits are partially overlapping, although the clinical picture of the present patient is among the few ones including congenital diaphragmatic hernia within the phenotypical spectrum. A more extensive comparative analysis of a larger number of patients with similar genetic profiles may allow for a more precise clinical and genomic characterization of this rare syndrome, and for genotype-phenotype correlations.