The Autistic.co.il portal is committed to expanding knowledge and understanding of the diverse manifestations of the Autistic Spectrum and related conditions. New scientific research, recently published in the J Hum Genet journal in October 2026, sheds light on an exceptionally rare syndrome called SSR4-CDG, presenting findings that may contribute to a broader understanding of the connection between genetic conditions and neurological manifestations, including characteristics of the Autistic Spectrum.

SSR4-CDG syndrome is an extremely rare inherited metabolic disorder, known as part of the group of "Congenital Disorders of Glycosylation" (CDG). It is caused by genetic changes in the SSR4 protein, which is essential for cellular processes in the body. To date, very few cases of this syndrome have been documented, and understanding of its clinical course, particularly its long-term implications, has been limited.

New Cases Illuminate the Picture

The current study reports on two unrelated patients diagnosed with SSR4-CDG through whole-exome sequencing. These cases provide new insights:

  • First Patient: Diagnosed with a new (de novo) genetic change in the SSR4 protein. He exhibited significant intellectual disabilities and characteristics indicative of being on the Autistic Spectrum. A particularly important point is the fact that the patient, now 56 years old, is alive and relatively healthy for his age, providing valuable information on the long-term course of the disease. Until now, no cases of patients with this syndrome reaching such an advanced age were known.
  • Second Patient: Diagnosed with an inherited genetic change received from his mother, which was initially classified as having uncertain significance. He exhibited severe developmental delay, growth difficulties, epilepsy, and hyperkinesia. After thorough examination including glycan analysis, RNA tests, and structural modeling, his genetic change was classified as likely pathogenic.

Expanding Understanding and Challenges

These findings expand existing knowledge regarding the clinical and genetic manifestations of SSR4-CDG syndrome. They highlight the diverse range of neurological manifestations that can accompany this condition, and the possibility of living with it into adulthood. For the adult Autistic community, these discoveries, although dealing with a rare syndrome, sharpen the understanding that even in complex and rare genetic conditions, diverse neurological manifestations that may include characteristics of the Autistic Spectrum can occur.

The study also emphasizes the challenges in accurately diagnosing genetic changes, especially when accompanied by subtle biochemical changes. It points to the importance of combining several testing methods - genetic, biochemical, and structural - to reach a correct and accurate diagnosis.

It is important to remember that this is a single study describing a small number of cases. While it provides important insights, further research is needed to expand understanding of SSR4-CDG syndrome and the complex connections between genetics, neurological development, and the Autistic Spectrum.