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More than 30 patients have been reported.

Facial characteristics include triangular face with a relatively large skull, large anterior fontanelle, prominent veins especially on the scalp, sparse scalp hair, decreased eyebrows and eyelashes, small mouth, and micrognathia. Natal teeth represent a common, but variable finding. The clinical spectrum is broad but intrauterine growth retardation and decreased subcutaneous fat have been reported as cardinal features. Mild to moderate intellectual disability is common. In survivors, a progressive ataxia and tremor develops later on. The syndrome is usually lethal in the first year of life but, on rare occasions, patients have survived into adulthood.

The syndrome is caused by bi-allelic variants in POLR3A located at 10q22.3, which encodes a subunit of RNA polymerase III. The syndrome is allelic with 4H leukodystrophy and adolescent-onset progressive spastic ataxia.

The diagnosis can be suspected by the clinical presentation and confirmed by molecular genetic testing.

The syndrome can resemble the allelic conditions 4H leukodystrophy and adolescent-onset progressive spastic ataxia, and may also resemble endosteal sclerosis-cerebellar hypoplasia syndrome which is caused by variants in POLR3B. Other entities to be considered are Hutchinson-Gilford progeria syndrome, Nestor-Guillermo progeria syndrome, Fontaine syndrome, SHORT syndrome, and Marfan syndrome lipodystrophy type.

Reliable prenatal diagnosis is possible if a pathogenic variant has previously identified in a family member.

Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing variant) informing them that there is a 25% risk of having an affected child at each pregnancy.

No specific treatment is possible. General supportive care including help in coping with the progressive nature of the disorder is indicated.

Many reported patients died in the first year of life; however, survival into adulthood has also been reported. Survival beyond infancy and childhood is likely possible nowadays using careful, supportive care.