Renpenning Syndrome

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Renpenning syndrome


Renpenning syndrome is an inherited X-linked disorder that manifests itself in males. It is characterized by mental retardation, short stature, a smaller than normal head circumference (microcephaly), and small testes. The syndrome was first described by Hans Renpenning, in 1962, in a large Mennonite family living in Manitoba, Canada. The term "Renpenning syndrome" came to be used as a general designation for X-linked mental retardation . However, as the syndrome has been mapped to Xp11.2-p11.4, the term "Renpenning syndrome" should be limited to the condition that maps to this region and is characterized by severe mental retardation, microcephaly, short stature, and small testes. The prevalence is unknown.


Renpenning syndrome is among the group of genetic disorders known as X-linked mental retardation (XLMR) syndromes. Developmental delay is present early with males learning to walk at age 2–3 years and able to say simple words at age 3–4 years. Although an affected male may appear physically normal, his head circumference and height will be at the lower limits of normal. After puberty, testes will be smaller than normal. Diagnosis is very difficult especially if there is only one male with mental retardation in a family. The diagnosis is exclusively based on evidence of inheritance of the above clinical findings in an X-linked manner and localization to the short arm (Xp11.1-p11.4) of the X chromosome .

Genetic profile

Renpenning syndrome is caused by an alteration in an unknown gene located on the short arm (Xp11.2-p11.4) of the X chromosome. The altered gene in affected males is inherited, in most cases, from a carrier mother. Since males have only one X chromosome, a gene mutation on the X is fully expressed in males. Carrier females, with one normal X chromosome and one affected X chromosome, do not have any of the phenotype associated with Renpenning syndrome.

Female carriers have a 50/50 chance of transmitting the altered gene to a daughter or a son. A son inheriting the altered gene will have Renpenning syndrome. The affected son will likely not reproduce.


Only males are affected with Renpenning syndrome. Carrier females do not express any of the signs or symptoms. Although Renpenning syndrome has been reported in a single Canadian family, it is believed to be present in all racial/ethnic groups.

Signs and symptoms

Manifestations of Renpenning syndrome may be present at birth. One male was reported to have global developmental delay at birth. All affected males had delay in reaching developmental milestones—by walking at age 18–24 months and having little or no speech by age three.

Affected males have a small head circumference (microcephaly), are of short stature, and have small testes. Facial features may include central balding, an upslant to the eye openings, and a short distance between the nose and the upper lip. Other clinical findings present in some of the affected males are blindness, seizures and diabetes mellitus.

Mental impairment is severe with IQ ranging from 15 to 40.


The diagnosis of Renpenning can tentatively be made on the basis of the clinical findings, including an analysis of the family history for evidence of X-linked inheritance. Linkage or segregation analysis using DNA markers in Xp11.4-p11.2 would be warrented to possibly rule out other X-linked mental retardation syndromes. Unfortunately, there are no laboratory or radiographic changes that are specific for Renpenning syndrome.

Sutherland-Haan syndrome , another X-linked mental retardation syndrome, also has microcephaly, short stature, small testes, and upslanting of the eye openings. Furthermore, this syndrome is localized from Xp11.3 to Xq12, which overlaps with the localization of Renpenning syndrome. However, males with Sutherland-Haan also have spasticity, brachycephaly (disproportionate shortness of the head), and a thin appearance. It is possible these two syndromes have different mutations in the same gene.

The Chudley-Lowry syndrome, which also has microcephaly, short stature, and small testes, has yet to be localized. However, males have distinct facial features, similar to those observed in XLMR-hypotonic facies, and obesity. As this syndrome has not been mapped, it is possible that Chudley-Lowry syndrome results from a mutation in the same unknown gene responsible for Renpenning syndrome.

Three other X-linked mental retardation syndromes (Borjeson-Forssman-Lehman, X-linked hereditary bullous dystrophy, and XLMR-hypotonic facies) have microcephaly, short stature, and small testes. However, these conditions are located in different regions on the X chromosome and can be ruled out if DNA marker analysis is done in the family.

Treatment and management

There is neither treatment nor cure for Renpenning syndrome. Early educational intervention may prove to be of some benefit for affected males. As some males have had seizures or diabetes mellitus, medication to control these conditions may be required at some point. Also some males may become blind. Some affected males may eventually have to live in facilities outside the home.


Life threatening or other health concerns have not been associated with Renpenning syndrome. However, the presence of severe mental impairment likely will result in some affected males living in a more controlled environment outside the home.



Fox, P., D. Fox, and J. W. Gerrard. "X-linked mental retardation: Renpenning revisited." American Journal of Medical Genetics 7 (1980): 491-495

Renpenning, H., et al. "Familial sex-linked mental retardation." Canadian Medical Association Journal 87 (1962): 954-956

Stevenson, R. E., et al. "Renpenning syndrome maps to Xq11." American Journal of Human Genetics 62 (1998): 1092-1101

Charles E. Schwartz, PhD