Physicians know Lenz-Majewski syndrome as a type of hyperostotic short stature associated with cutix laxa and osteosclerosis. The syndrome is based on a mutation of gene PTDSS1 on gene locus 8q22.1. Causal therapy is not yet available for affected individuals.
What is Lenz-Majewski syndrome?
Lenz-Majewski syndrome is a specific and extremely rare form of short stature. The symptom complex has been described in only nine cases to date. As a syndrome belonging to the group of hyperostotic short stature, the complex is characterized by characteristic facial features and cutis laxa in addition to short stature. Progressive bone sclerosis was also observed in the new cases described. Progressive sclerosis is also known as osteosclerosis and corresponds to hardening of bone tissue. As a prevalence, Lenz-Majewski syndrome is thought to have only one case per million people. Synonyms for the symptom complex are the clinical terms Braham-Lenz syndrome and Lenz-Majewski hyperostotic dwarfism. The former synonym can be traced back to the first describer, Braham. In the 20th century, he still referred to the syndrome as Camurati-Engelmann syndrome. A little later, the German human geneticist Lenz, together with the pediatrician Majewski, made the first delimitation. The designation of the disease as Lenz-Majewski syndrome refers to this initial delineation toward the end of the 20th century.
Causes
Lenz-Majewski syndrome has an underlying genetic cause. The cases observed to date do not appear to have occurred sporadically but are subject to autosomal dominant inheritance. Especially the high age of the fathers of affected children points to autosomal-dominant new mutations as the primary cause for the symptoms. Meanwhile, despite the few cases described, the causative gene could be identified. Thus, a mutation of the PTDSS1 gene, located at gene locus 8q22.1, probably underlies the syndrome. The gene codes for a protein called phosphatidylserine synthase 1. Mutation of the gene causes the protein to lose its function, which is to form phosphatidylserines. Phosphatidylserines are important phospholipids that are counted among the membrane components. This relationship seems to trigger the extreme short stature with pathologically altered vertebral bodies.
Symptoms, complaints, and signs
Patients with Lenz-Majewski syndrome suffer from various clinical criteria. For example, the disease manifests in early infancy and appears as failure to thrive during this period. The patients appear pre-aged and progeroid. Their cranial sutures are unusually wide. The same is true for their fontanelle. Often, craniofacial dysmorphia is already apparent immediately after birth. Most patients have a prominent and extremely broad forehead. In addition, hypertelorism is often present. The tear ducts of the affected persons are often more or less misaligned in their course. The auricles appear excessively large and conspicuously flabby. The enamel of the affected teeth is usually defective, which later promotes caries. The pre-aged appearance of those affected is due to a so-called cutis laxa. This phenomenon corresponds to thin and withered skin, which is increasingly marked by veins and is associated with hernias, cryptorchidism or hypospadias. Most patients suffer from mental retardation. On the fingers, the syndrome is manifested by membranous syndactyls, usually affecting the space between the second and fifth fingers. Severe short stature is the most characteristic symptom of Lenz-Majewski syndrome. In some circumstances, the limbs of affected individuals are additionally affected by brachydactyly and appear severely shortened.
Diagnosis and course of the disease
To make an initial tentative diagnosis of Lenz-Majewski syndrome, the clinical picture is usually sufficient for the physician. In addition, an x-ray may be ordered. The imaging shows typical criteria such as progressive osteosclerosis of the cranial bones and vertebral bodies. This sign may be associated with broad ribs or clavicles. In addition, diaphyseal sclerosis with widening of the bones may be seen on radiographs. Hypoplasia at the middle phalanges is also indicative of the syndrome.Differentially, the physician must distinguish the syndrome from symptom complexes with a similar appearance, such as Camurati-Engelmann syndrome, craniodiaphyseal dysplasia, or craniometaphyseal dysplasia. To confirm a suspected diagnosis beyond doubt, molecular genetic testing can be performed. If the patient does indeed have Lenz-Majewski syndrome, this analysis provides evidence of the genetically causative mutation.
Complications
As a result of Lenz-Majewski syndrome, affected individuals primarily suffer from short stature. In children, this complaint can lead to psychological problems or bullying and teasing. The quality of life of the affected person is considerably limited by this condition. Furthermore, it is not uncommon for caries and other defects to occur in the teeth. Without treatment, the affected person suffers from severe toothache and other unpleasant discomfort in the oral cavity. Not infrequently, Lenz-Majewski syndrome also leads to mental retardation, so that patients are dependent on the help of other people in their daily lives. Often, the parents and relatives of the affected persons also suffer from mental discomfort or depression as a result of the symptoms. Furthermore, individual extremities can also be shortened due to the disease, which can also lead to various restrictions in life. It is not possible to treat Lenz-Majewski syndrome causally. For this reason, treatment is mainly aimed at reducing the individual symptoms. Complications do not occur, but the course of the disease is not completely positive. As a rule, those affected by Lenz-Majewski syndrome are dependent on the help of other people throughout their lives.
When should you see a doctor?
Patients with Lenz-Majewski syndrome experience a variety of symptoms that need to be clarified. Because the condition is hereditary, symptoms can be diagnosed shortly after birth. Parents should consult closely with a physician in case of symptoms or complications. If the child develops mental problems as a result of the malformations and skin changes, a therapist must be consulted. Complications from any mental ailments should also be clarified by a professional. It is best for the parents to maintain contact with a specialist clinic for genetic diseases. Other physicians must be consulted if the child shows signs of visual disturbances or oral discomfort. The characteristic short stature must be treated by an orthopedist. If Lenz-Majewski syndrome is treated early, the symptoms can be greatly alleviated. Therefore, early diagnosis is necessary, even if the symptoms of hyperostotic short stature may not be pronounced at the beginning. The child will continue to need the help of physical therapists, psychologists, and physicians after initial treatment.
Treatment and therapy
To date, no causal therapeutic approaches are available for patients with Lenz-Majewski syndrome. Currently, however, gene therapy treatment pathways are a subject of medical research. Depending on the progress of this field of research, there may be gene therapy-based causal treatment options for the syndrome in the future. Currently, however, those affected must be satisfied with symptomatic treatment. This symptomatic treatment may include, for example, surgical correction of the malformations. Such correction does not always have to take place, but is limited to syndactyls that restrict the patient’s daily life. Progressive hardening of the bones may be slowed by dietary and drug interventions. Osteosclerosis should be monitored constantly and closely so that any fractures that occur can be treated quickly. Because of the mental and intellectual deficits, early intervention is usually recommended for affected patients. Within the framework of this early intervention, any intellectual deficits can ideally be reduced so that they are moderate and hardly noticeable. The parents of affected children ideally receive in-depth counseling regarding possible support options.
Outlook and prognosis
The prognosis of Lenz-Majewski syndrome is unfavorable. According to current medical and scientific knowledge, there is no therapeutic option that leads to recovery.The cause of the health disorder is based on a genetic defect. Since changes to human genetics may not be made for legal reasons, there is no way to correct the mutation. The further course of the disease depends on the severity of the individual symptoms. Nevertheless, the quality of life of a patient with the syndrome is basically considerably limited. Even with a mild manifestation of the symptoms, there are abnormalities in the growth process. A characteristic feature of the disease is short stature. This cannot be corrected even by the administration of hormones. The visual blemish leads to a state of emotional stress. For this reason, the risk of psychological sequelae is increased in those affected. In a severe course of the disease, cognitive impairments are present in addition to the physical abnormalities. The mental retardation can be supported by early intervention already in the first years of life. Cognitive performance is then improved overall, but there is a possibility that limitations in the level of performance will remain throughout life. The deficits can be minimized with the help of a therapist and support from family members. This allows some patients to lead a good life.
Prevention
To date, Lenz-Majewski syndrome cannot be prevented because the symptom complex is causally based on a new genetic mutation for an unidentified reason.
Follow-up
Because Lenz-Majewski syndrome is incurable, regular and comprehensive follow-up care is required. Affected individuals usually suffer from a number of complications and discomforts, which in the worst case can lead to the death of the affected individual in the process. The disease should therefore be recognized very quickly in order to contain further complaints or complications. Affected persons should see a doctor regularly to check the setting of the medication as well as possible side effects. Since the disease can be very stressful for the affected person and his or her relatives, psychological care may be recommended to reduce suffering in general.
What you can do yourself
It is not possible to treat Lenz-Majewski syndrome by means of self-help. As a rule, direct, medical treatment of the syndrome is also not possible, since it is a hereditary condition. If the affected person shows intellectual deficits, these must be remedied by intensive support. The earlier this support begins, the higher the probability of compensating for these deficits. Parents can also carry out various exercises with the child at home to promote and strengthen the mind. However, intensive promotion of the child should also take place in kindergarten and at school. The hardening of the bones can be alleviated by taking medication. Here, regular intake should be ensured, and parents should pay attention to this regularity, especially in the case of children. The hardening can also be stopped by an adapted diet. However, the doctor’s precise instructions on a special diet must be followed. The deformities are corrected by surgical intervention and cannot be treated by means of self-help.
