Renpenning syndrome is an X-linked syndrome of mental retardation. It is characterized by severe mental impairment, microcephaly, long and narrow face, short stature, small testes, and a lean body build. About a fifth of the patients have major malformations, including cardiac defects, anal malformations, coloboma, and cleft palate. Being X-linked, the syndrome is severe in affected males, while carrier females show little or no expression.

Renpenning syndrome is a fairly rare condition, with only a little more than 60 affected individuals described in about 15 families worldwide. Diagnosis is based on clinical features. Fragile X syndrome can be distinguished clinically from Renpenning syndrome by the lack of microcephaly in the former. Confirmed diagnosis would require the help of molecular methods. Treatment is symptomatic and supportive. There is usually no decrease in life expectancy.

Renpenning syndrome is inherited in an X-linked recessive manner, and is caused due mutations in the PQBP1 (Polyglutamine Binding Protein 1) gene. The protein coded for by this gene plays a major role in the transport and storage of RNA within cells, especially in the neurons. Mutations in the gene thus, interfere with normal brain development.

Some other X-linked mental retardation syndromes, such as Sutherland-Haan syndrome, Hamel Cerebropalatocardiac syndrome, MRX55, Golabi-Ito-Hall syndrome, and Porteous syndrome have all now been shown to be genetically the same entity as Renpenning syndrome.