We reported a rare case of 1p36 deletion syndrome diagnosed using whole-exome sequencing (WES) in a Tunisian neonate, and to highlight the utility of WES in detecting structural variants, particularly in resource-limited settings. Clinical and genetic investigations were conducted on a female neonate presenting with a severe polymalformative syndrome. WES was performed to detect potential genetic abnormalities, followed by validation through fluorescence in situ hybridization (FISH). Variant annotation and classification were done in accordance with ACMG guidelines. WES identified a heterozygous interstitial deletion in the 1p36 region, spanning 11.64 Mb and affecting 155 coding genes, including key genes such as MMP23B, GABRD, SKI, PRDM16, KCNAB2, RERE, UBE4B, and CASZ1. The deletion was classified as pathogenic, and FISH analysis confirmed its presence. Clinically, the patient exhibited intrauterine growth restriction, neonatal epilepsy, craniofacial dysmorphia, congenital heart defect, and agenesis of the corpus callosum. This is the first reported case in Tunisia of a 1p36 deletion identified via short-read WES. The findings support the expanding role of WES in structural variant detection and underscore its diagnostic value, especially in settings with limited access to chromosomal microarray or genome sequencing technologies.

This report describes a nine-year, five-month-old Saudi girl with 1p36 deletion syndrome (1p36DS) referred for dental evaluation due to esthetic concerns. Clinical and radiographic assessment revealed multiple carious lesions, poor oral hygiene, dens invaginatus in maxillary incisors, infraocclusion of a primary molar, and, notably, agenesis of all primary and permanent canines except for one retained mandibular primary canine. Additionally, two supernumerary maxillary incisors (mesiodens) were identified, causing severe rotation of adjacent teeth, a combination of dental anomalies not previously documented in 1p36DS. A comprehensive treatment plan was executed, encompassing preventive measures, restorative care, surgical extraction of mesiodens, and interceptive orthodontic alignment using a 2×4 fixed appliance and transpalatal arch. These interventions led to improved esthetics, dental function, and psychosocial confidence. The management of 1p36DS patients requires a multidisciplinary approach due to the conjunction of craniofacial and systemic anomalies. Pediatric dentists play a crucial role in early detection, preventive care, and timely interventions, all of which contribute to enhanced function and quality of life. Routine panoramic imaging and vigilance for atypical dental patterns are critical for guiding genetic referrals and comprehensive care. This case broadens the known phenotypic spectrum of 1p36DS by documenting a novel dental presentation involving concurrent agenesis of both primary and permanent canines with supernumerary maxillary incisors. Early recognition of such anomalies enables timely diagnosis, personalized management, and multidisciplinary collaboration, emphasizing the vital role of pediatric dentists in the holistic care of patients with rare chromosomal disorders.

Chromosome 1p36 deletion syndrome is the most common terminal autosomal deletion disorder. While postnatal features are well-defined, prenatal characterization remains less comprehensive. This study aims to delineate the prenatal sonographic and genetic spectrum of this syndrome and explore genotype-phenotype correlations. A retrospective analysis was conducted on 21 consecutive prenatally diagnosed cases of 1p36 deletion (2017–2025) from a single tertiary center. Data on maternal demographics, ultrasound findings, genetic results, inheritance patterns, and pregnancy outcomes were collected. A pooled analysis included 10 isolated cases (with complete ultrasound data) from our cohort and 33 previously reported cases. The cohort demonstrated a strong female predominance (71.4%, 15/21). Fifteen (71.4%) involved isolated 1p36 deletions, while six (28.6%) exhibited additional chromosomal aberrations. Pooled analysis of 43 prenatally diagnosed isolated cases (10 current and 33 published) revealed brain anomalies to be the most common prenatal feature (58.1%, 25/43), with ventriculomegaly (37.2%, 16/43), corpus callosum hypoplasia (9.3%, 4/43), and choroid plexus cysts (9.3%, 4/43) being the most frequent subtypes. Cardiac defects were observed in 39.5% (17/43) of cases, predominantly atrial/ventricular septal defects (ASD/VSD, 23.3%, 10/43) and Ebstein anomaly (11.6%, 5/43). Other frequently observed features included increased nuchal translucency (16.3%, 7/43) and single umbilical artery (14%, 6/43). Parental genetic analysis demonstrated de novo deletions in 80.0% (12/15) of cases, while 20.0% (3/15) were inherited from phenotypically normal parents. Congenital brain anomalies (particularly ventriculomegaly) and cardiac defects are hallmark prenatal features of isolated 1p36 deletion syndrome. Our findings underscore the role of key genes (RERE, SPEN, PRDM16, MMP23B) in shaping the phenotype and highlight the importance of parental genetic testing in counseling, given the potential for inherited variants with variable expressivity.

The intrauterine ultrasound phenotype, genotype, pregnancy outcome, and neonatal prognosis of fetuses with 1p36 deletion syndrome were retrospectively analyzed, as previous reports are limited. Pregnant women (25,000) who underwent interventional prenatal diagnosis between December 2016 and March 2024 were selected. Fetal villus tissue, amniotic fluid, or umbilical cord blood were extracted for single nucleotide polymorphism array (SNP-array) detection under ultrasound guidance. Thirteen fetuses had 1p36 deletions involving fragments that were 0.46-22.5 Mb. Six and seven fetuses had large and small copy number variation (CNV) fragment deletions in the 1p36 region, respectively. Two fetuses had normal ultrasound phenotypes, three underwent early spontaneous abortion, one had isolated ventricular septal defect, one had isolated mild ventriculomegaly, two had mild ventriculomegaly associated with increased renal echogenicity, one had mild ventriculomegaly associated with ventricular septal defect, one had severe ventriculomegaly associated with ventricular septal defect and fetal growth restriction, one had tricuspid valve dysplasia, and one had nasal bone dysplasia. Three 1p36 deletions were de novo, and one was paternally inherited. There were three cases of early spontaneous abortion, seven terminations, and three routine postnatal follow-ups. High-resolution SNP-arrays are suitable for the prenatal diagnosis of 1p36 deletion syndrome.