818 - First Reported Case of Witteveen-Kolk Syndrome in Puerto Rican Twins: Clinical Presentation and Genetic Findings

Case Diagnosis: Witteveen-Kolk syndrome (WITKOS) (OMIM 613406) is a neurodevelopmental disorder caused by heterozygous loss-of-function mutations in the SIN3A gene, first identified in 2016.  It is characterized by developmental delay, intellectual disability, microcephaly, short stature, subtle anomalies on brain MRI, and distinctive facial features. Common facial features included a broad, tall forehead; small mouth, thin upper lip with pointed chin and down-slanting palpebral fissures. To date, about 50 patients have been reported in the medical literature.

Case Description:

We present the case of 2-year-old twin boys from Puerto Rico, born at 34 weeks’ gestation via cesarean section after an uncomplicated pregnancy to a 30-year-old G3P1A1 mother. Both twins presented with developmental delay, with notably delayed speech and communication skills, hypospadias and obstructive sleep apnea (OSA). Twin A presented with distinctive facial features, as well as myelomeningocele and hydrocephalus, which further impacted his development.
In addition to the twins’ clinical presentation, whole exome sequencing (WES) genetic exam identified a SIN3A mutation, confirming the diagnosis of WITKOS.

Discussions: To our knowledge, this is the first reported case of Witteveen-Kolk syndrome reported in Puerto Rico. This case involving twins provides a rare opportunity to observe and compare the phenotypic variability despite the same SIN3A mutation, emphasizing the need for genetic testing and awareness of WITKOS in diverse populations for accurate diagnosis and counseling.

Conclusions: WITKOS is a rare neurodevelopmental disorder characterized primarily by developmental delay, especially in language and speech, intellectual disability, and distinctive facial features. This report expands the phenotypic spectrum by documenting the first cases in Puerto Rican twins, illustrating both shared and unique manifestations. Recognition of WITKOS in diverse populations and among siblings provides critical insights for timely diagnosis, genetic counseling, and management.