Description of a new severe variant of Sotos syndrome

*Correspondence: [e-mail].

Abstract

Case Presentation: Late preterm male newborn, delivered by cesarean section due to polyhydramnios and fetal macrosomia, was born with good vitality. The mother had gestational diabetes, with no other important antecedents during pregnancy. The baby had birth weight, length and head circumference above the 98th percentile. In the neonatal period, he presented hypoactivity, dysphagia and drowsiness, without other associated symptoms, being discharged on the 16th day after normal neonatal screenings, diet progression and symptom improvement. During follow-up, the patient had several hospitalizations due to respiratory conditions. In addition, he evolved with notable hypotonia and dysphagia, requiring gastrostomy. Beyond that, the patient had a head circumference and length maintained close to the P98%, with significant developmental delay (Head erect and steady at age 6 months, sits without support at age 9 months, patient still does not walk holding onto furniture, eats by mouth or vocalizes without crying at 1 year and 1 month old). Progressive facial dysmorphism and scoliosis become evident at age 1 year. On investigation, laboratory tests, cranial MR with spectroscopy, fundoscopy, expanded newborn screening and CGH ARRAY were normal. In Exome, a probably pathogenic heterozygous variant in the NSD1 gene (NM_172349.2): c.3625del:p (Ala1209GinfsTer9) was identified. This variant not yet described in the literature is expected to cause loss of function of an allele, which leads to pathogenicity related to Sotos Syndrome and is not present in population databases. The diagnosis of Sotos syndrome was made by relating the variant to the clinical picture.

Discussion: Diagnosing Sotos syndrome at first glance can be challenging due to the broad spectrum of the initial clinical presentation. There are patients with multiple congenital anomalies and neonatal complications and there are patients with relatively normal physical examinations. Furthermore, confounding factors such as anthropometric proportionality at birth may be present. The learning disability ranges from mild (affected individuals live independently) to a severe learning disability. However, cardinal characteristics in the medium and long term become evident and should refer to the diagnosis.

Final Comments: This report describes a new variant with findings of severe symptoms such as dysphagia requiring gastrostomy, scoliosis before the first year of life, significant developmental delay and early impairment in socialization.

Publication History

Article published online:
12 May 2025