Renpenning Syndrome

By | June 8, 2022

Renpenning syndrome is an inherited disorder belonging to the group of cognitive retardation disorders. The clinical picture is now assigned to the Golabi-Ito-Hall syndrome, the cerebro-palato-cardiac syndrome type Hamel, the Porteous syndrome, the Sutherland-Haan syndrome, MRX55 and other syndromes of the XLMR families. Therapy is supportive.

What is Rennenning Syndrome?

Cognitive retardation is a group of disorders characterized by below-average mental abilities. Such illnesses are usually associated with a limitation of affective behavior. Mental disabilities are also mentioned in the corresponding group of diseases. For what does cls stand for, please visit

The causes of such conditions can be of different nature. Most cognitive retardations are congenital disorders. One such disease is Renpenning syndrome. The exact prevalence of the disease is not yet known. However, estimates assume that fewer than one person per 1,000,000 inhabitants is affected. Like all syndromes, Renpenning syndrome is a complex of different symptoms.

In addition to cognitive retardation, there are usually skeletal changes. The symptom complex is assigned to the malformation syndromes. The name goes back to the Canadian pediatrician Hans Jacob Renpenning and his associates, who first described the syndrome in the mid-20th century. A synonym for the Renpenning syndrome is the expression of the X-chromosomal intellectual disability type Renpenning.


Renpenning syndrome is a congenital disease with a hereditary basis. The symptom complex is therefore assigned to the hereditary diseases and has its cause in the genes. Inheritance is X-linked, but sporadic cases without familial clustering have also been documented.

Because of the X-linked inheritance, males are more frequently affected by the syndrome than females. The primary cause of the symptom complex is a genetic mutation. This change in genetic material was localized to the PQBP1 gene in the gene locus Xp11.23, which encodes an endogenous protein.

This protein is the polyglutamine tract-binding protein 1, which in its physiologically intended form regulates the transcription and the splicing process in cell nuclei of the pre-mRNA. Seven different mutations of the associated gene are known to date. These are six chain-terminating mutations that result in a truncated protein. One of the mutations corresponds to a missense mutation.

The Golabi-Ito-Hall syndrome, the cerebro-palato-cardiac syndrome type Hamel, the Porteous syndrome, the Sutherland-Haan syndrome, MRX55 and other syndromes of the XLMR families are now assigned as phenotypic variants of the disease.

Symptoms, Ailments & Signs

Renpenning syndrome manifests itself as a key symptom in mental retardation. Accompanying symptoms, the patients usually show microcephaly (small head) and short stature. Some patients have a small testicular volume. Female carriers usually show no symptoms.

The affected males are conspicuous from birth due to their low brain mass. Characteristically, they show skeletal abnormalities in the facial area. In addition to a long and triangular facial area with a slanting eyelid, they often have hairless eyebrows, a bulbous nose with a protruding columella, or ears that protrude in the shape of a spoon.

Because of failure to thrive, patients remain lean. Motor and language development is delayed from the start. A third of the patients have little or no intellectual disability. Muscular atrophy in the back leads to a drooping of the head, which is accompanied by a loss of normal back curvature and gives the impression of a scapula winged.

The metacarpophalangeal joint of the thumb is often pathologically altered. The hand muscles are partially affected by intrinsic tissue breakdown. Congenital heart defects, cleft palate, coloboma of the eyes or ani imperforati are less common.

Diagnosis & course of disease

Diagnosis of Renpenning syndrome requires proof of the inherited mutation. The first suspected diagnosis is made on the basis of the clinical symptoms. The process often turns out to be difficult. Male patients with intellectual disability without a proven family history often distract physicians from a diagnosis, although the syndrome can also occur sporadically.

Magnetic resonance imaging of the brain shows contrasts with the pronounced microcephaly. The molecular diagnostic analysis of the PQBP1 gene secures the diagnosis. In terms of differential diagnosis, the phenomenon must be differentiated from fragile X syndrome by means of evidence of microcephaly. Fetal CMV infection, fetal alcohol syndrome and similar phenomena must also be distinguished.

If the gene mutation is identified in the family, prenatal diagnostics can take place. The prognosis of the patient depends on the severity of the symptoms in the individual case. Hamel-type cerebro-palato-cardiac syndrome is associated with the most unfavorable prognosis. However, life expectancy is usually not limited.


Despite the physical and mental limitations and the incurability of the hereditary Renpenning syndrome, life expectancy is usually not shortened. The prerequisite for this is, of course, intensive symptomatic therapy and support. However, two-thirds of patients with this syndrome require lifelong care because of mental retardation.

This applies to both intellectual development and proper nutrition. Many of those affected suffer from failure to thrive as a result of malnutrition and anorexia, which can only be managed within the framework of comprehensive symptomatic therapy. The failure to thrive also exacerbates the development and growth disorders. In severe cases, the child can also die from undernutrition or malnutrition.

All patients suffer from muscular atrophy of the back muscles. A scapula alata can develop from this, which is characterized by a wing-like protrusion of the shoulder blade from the thorax. In rare cases, heart defects, cleft palate or clefts in the eye area also occur. Patients with heart defects require special medical supervision to avoid further complications.

Life-threatening complications usually do not occur with Renpenning syndrome. In addition to the failure to thrive, mental and physical impairments, mental illnesses can also occur as a complication as a result of these stresses. Therefore, such obvious deformities as cleft palate or clefts around the eyes should be surgically corrected. Psychotherapeutic therapy is also recommended for those affected.

When should you go to the doctor?

Since Renpenning syndrome is a hereditary disease, it can only be treated purely symptomatically and not causally. A complete cure cannot be achieved. If the person affected by Renpenning syndrome wishes to have children, genetic counseling can also be carried out in order to avoid inheriting the syndrome.

A doctor should be consulted if the person concerned suffers from short stature. Above all, the parents of the child must recognize this and then consult a doctor. A doctor should also be consulted immediately in the case of general failure to thrive in order to ensure the normal development of the child. This can avoid further complications. Since Renpenning syndrome is also associated with heart defects, the person affected should be examined regularly.

The first diagnosis of Rennenning syndrome can be made by a pediatrician or by a general practitioner. However, further treatment depends very much on the exact severity of the symptoms and is carried out by various specialists.

Treatment & Therapy

Renpenning syndrome has so far been considered an incurable disease. Since the cause is a genetic mutation, a causal treatment would have to start with the genes themselves. Although gene therapy approaches are currently a focus of medical research, they have not yet reached the clinical phase.

For this reason, only supportive and symptomatic treatment measures are currently available for people with Renpenning syndrome. If there are heart defects, the correction of the organic defects is the focus of the therapy. The mental development of the patients is supported as far as possible by early educational supportive measures.

Those affected are cared for by an interdisciplinary team of doctors. Experienced therapists treat all associated symptoms depending on their severity. Physiotherapy and ergotherapeutic measures teach those affected and their parents how to deal with motor deficits.

Because of the learning disability, patients are advised to take specific remedial courses at school. In severe cases, the parents may receive psychotherapeutic support in dealing with everyday life. Genetic counseling is indicated for planned pregnancies in the future.


So far, Renpenning syndrome can only be prevented by genetic counseling. In the case of an existing pregnancy and family proven disposition, a prenatal diagnosis can be carried out, after which couples can decide against the child if necessary.


Affected people with Renpenning syndrome usually only have very limited direct aftercare measures available, since it is a congenital disease that usually cannot be completely cured. Therefore, sufferers should ideally consult a doctor at the first signs and symptoms of the disease and also initiate treatment to prevent the occurrence of other symptoms.

Genetic testing and counseling is also very useful if you want to have children, in order to prevent the syndrome from occurring in the offspring. Most of those affected are dependent on physiotherapy and physiotherapy measures for Renpenning syndrome. These exercises should be carried out regularly, although it is also possible to repeat them at home.

This can alleviate most of the symptoms. The intake of various medications is also very important. The person concerned should always follow the instructions of the doctor and pay attention to the prescribed dosage and also to the regular intake of the medication. If anything is unclear or you have any questions, it is advisable to consult a doctor first.

You can do that yourself

Renpenning syndrome is a very rare hereditary disease that cannot be treated causally. Therapy focuses on relieving individual symptoms.

Parents of affected children are exposed to great mental as well as physical stress reactions. Psychological support helps to accept the difficult illness and to learn how to deal with it in the long term. The affected children must be cared for permanently. Contact with nursing services, special schools and the like should be established at an early stage. In addition, medical check-ups must be taken advantage of and the medication must be regularly adjusted. To a limited extent, the mental disorders can be treated with targeted training. It is advisable to consult with different specialists during the illness and to gather all available information about the rare disease.

Some of the physical disabilities can be treated surgically. Depending on the severity of the syndrome, however, adjustments in the household are necessary, such as the installation of disabled-friendly stairs and sanitary facilities. The affected person should establish contact with other patients who have Renpenning syndrome. Especially for small children, the exchange with like-minded people is important in order to accept the suffering.

Renpenning Syndrome