phocomelia

Generality

The phocomelia is a very rare congenital disease, which induces the appearance of anatomical abnormalities at the level of: upper limbs, lower limbs, head, face, internal organs and so on.

It may be the result of a genetic mutation affecting chromosome 8, inherited from the parents (hereditary phocomelia), or the consequence of improper assumption by the mother during pregnancy of some drugs such as thalidomide or accutane (phocomelia iatrogenic).

Doctors have the opportunity to diagnose phocomelia before birth, thanks to a simple prenatal ultrasound.

The treatments envisaged consist of therapeutic remedies aimed at improving the symptomatology and quality of life; for example, they are widespread: the application of prostheses, for the replication of upper or lower limbs, and the use of orthopedic braces.

Recalls of genetics

Before proceeding with the description of the phocomelia, it is useful to review some fundamental concepts of genetics.

What is DNA? It is the genetic heritage in which the physical features, predispositions, physical qualities, character, etc. are written. of a living organism. It is contained in all the cells of the body having a nucleus, as it is inside this one.

What are chromosomes? According to the definition, chromosomes are the structural units in which DNA is organized. The human cells contain, in their nucleus, 23 pairs of homologous chromosomes (22 of an autosomal non-sexual type and a couple of sexual type); each pair is different from another, as it contains a specific gene sequence.

What are genes? They are short stretches, or sequences, of DNA with a fundamental biological meaning: from them, in fact, proteins are derived, that is, fundamental biological molecules for life. In genes, there is "written" part of what we are and what we will become.

Each gene is present in two versions, the alleles: an allele is of maternal origin, then transmitted by the mother; the other allele is of paternal origin, therefore transmitted by the father.

What is a genetic mutation? It is an error within the DNA sequence that forms a gene. Because of this error, the resulting protein is defective or completely absent. In both cases, the effects can be deleterious both for the life of the cell, in which the mutation occurs, and for that of the organism in its totality. Congenital diseases and neoplasms (or tumors) are responsible for one or more genetic mutations.

What is the phocomelia?

Phocomelia is a very rare congenital disease that causes more or less severe anatomical deformations in the limbs, head or internal organs.

Phocomelic individuals, in fact, are people who may have malformed arms and / or legs (if not entirely absent), hands with fingers fused to each other, deformed ears and eyes, feet directly connected to the torso, underdeveloped lungs or absent, etc.

In medicine, the term "congenital" referring to a pathology means that the latter is present from birth.

ORIGIN OF THE TERM

Coining the term phocomelia was a French biologist named Etienne Geoffroy Saint-Hilaire, in 1836.

Causes

The phocomelia can be the consequence of a genetic mutation of DNA, transmitted from parents to the sick individual, or of a prenatal assumption, by the mother of the affected subject, of drugs such as thalidomide (against morning sickness) and accutane (isotretinoin, against acne).

In other words, phocomelia exists both as an inherited disease and as an iatrogenic disease .

FOCOMELIA AS HEREDITARY DISEASE

Phocomelia in its hereditary form is a genetic disease with autosomal recessive transmission, which occurs due to mutations of specific gene sequences present on the autosomal chromosome 8 .

For an inexperienced reader of genetics, this definition could be completely incomprehensible, therefore it is good to clarify what are the genetic diseases with autosomal recessive transmission (or recessive hereditary diseases).

These pathologies are expressed only when both alleles of the gene that causes the disease have changed - this is because the mutated allele is recessive over the healthy one - and only when both parents are carriers of at least one mutated allele.

Summary of the meaning of the terms hereditary, autosomal and recessive

Hereditary: means that parents transmit to the offspring (ie the children) the genetic alteration responsible for the disease.
Autosomal: means that the mutation responsible for the disease lies in a non-sexual chromosome, therefore autosomal.
Recessive: means that the disease causes symptoms and signs only when both alleles of the responsible gene are mutated. To simplify the concept, it is as if one mutated allele did not have enough power to influence the healthy allele, which continues to perform its action normally.

Figure: general example of an autosomal recessive genetic disease (or recessive inherited disease). Individuals with a mutated allele only take the name of healthy carriers, as they possess a genetic anomaly that they can transmit to their children but, at the same time, they are asymptomatic (ie they do not present any disturbance).

In probabilistic terms, the union of two healthy carriers means that: 25% of children are sick, another 25% are completely healthy and the remaining 50% are healthy carriers.

FOCOMELIA AS IATROGENA DISEASE

Phocomelia in its iatrogenic form is associated above all with the mother's intake of thalidomide during pregnancy.

To put this drug on the market, without the need for any medical prescription, was a German pharmaceutical company, in 1958. Initially, the doctors advised it as a sedative for the treatment of anxiety; later, as a medicine against morning sickness typical of pregnancy.

Since its commercialization with this second purpose, in Germany (above all) and in all those countries that bought the license, there has been a noticeable increase in the cases of phocomelia, so that it was quite simple to establish whose responsibilities they were.

Consider that, according to the chronicles of the time, because of thalidomide they were born with the phocomelia between 5, 000 and 7, 000 individuals, 40% of whom did not survive the vicissitudes of birth or the first months / years of life. Furthermore, the same statistics from the period report that 50% of the phocomelic mothers had taken thalidomide in the first three months of pregnancy.

Immediately after the discovery of the harmful action of thalidomide against the fetus, starting in 1961, the health authorities of the various countries involved withdrew the aforementioned drug from the trade.

In recent years, doctors and pharmacologists have revived the use of thalidomide as a medicine for the treatment of multiple myeloma .

Epidemiology

The doctors have not yet established what the exact incidence of phocomelia is in its hereditary form. Surely, they consider it a very uncommon pathology.

According to various statistical surveys, the prevalence in males is similar to that in women, so men and women are affected approximately equally.

Symptoms and Complications

To learn more: Symptoms Phocomelia

The hereditary phlegm can produce very varied symptoms. In general, the most common clinical manifestations consist of:

Deformations of the upper limbs . These are the most common abnormalities in phocomelic patients. They come from the arms too short or absent in the presence of hands with fingers fused together (syndactyly) or missing (oligodactyly).
There are also cases in which the arms are missing, but not the hands, therefore the patient presents the latter where the upper limbs should begin.
Deformations of the lower limbs . Some examples of such deformations are: feet with fused or missing fingers, legs too short, lack of legs but no feet (the latter are attached to the pelvis) etc.
Micrognathia . In pathological anatomy, this term indicates the insufficient congenital or acquired development of the jaw. The presence of micrognathia generally implies a strong reduction in the size of the chin and different speech disorders.
Cleft lip (or cleft lip) and / or cleft palate . The first condition consists of an interruption at the level of the upper lip, while the second consists of an interruption of the palate.
Cryptorchidism (or retained testicle) . It consists in the failure of one or both testicles to descend into the scrotum, a process that generally takes place after birth, exactly during the first year of life. The testicles that do not descend are still at abdominal level or along the inguinal canal (between abdomen and scrotum).
Microcephaly . It is the medical term that indicates a reduced development of the skull.
Ocular hypertelorism . With ocular hypertelorism, doctors indicate the presence of two eyes that are particularly distant from each other.
Ocular sclera of blue-blue color .
Small and underdeveloped nose, with very thin nostrils .
Deformed ears .
Scattered presences of tufts of light blond hair .
Presence of a hemangioma on the face . Hemangiomas are benign tumors of endothelial cells, which usually cover blood vessels. Generally, they appear as a dense collection of capillaries, which form a superficial or deep nodule.
Alteration of cognitive development .
Slow intra-uterine development .
Slow infant growth .

SIGNS AND SYMPTOMS OF THE MOST RESTFUL FORMS OF HEREDITARY FOCOMELIA

The signs and symptoms that characterize the most serious forms of hereditary phlegm are:

The encephalocele . It consists of the exit, through an anomalous opening on the skull, of meningeal / cerebral tissue. Doctors describe this malformation as cerebral hernia.
At its origin there is the failure to weld the skull.
Hydrocephalus . It is the medical term that indicates an abnormal increase in the cerebrospinal fluid, contained in the subarachnoid space and in the cerebral ventricles. The presence of hydrocephalus mainly causes headaches, epilepsy attacks, convulsions and vomiting.
The hypospadias . It is a purely male condition, which consists in an incorrect positioning of the opening of the urethra. This, in fact, does not reside at the tip of the glans, but at a point along the ventral side of the penis.
The bicorne uterus . It is a malformation of the uterus, in the presence of which this fundamental female genital organ takes on the ideal shape of a heart and presents itself with two "horns".
The short neck .
Thrombocytopenia (or thrombocytopenia) . It is the medical term that indicates a low level of platelets (less than 150, 000 units per mm3 of blood). The platelets are those corpusculated elements of the blood (the others are the red blood cells and the white blood cells), which intervene in the process of blood coagulation.
The presence of opaque corneas, cataracts and / or eyelid defects
The presence of renal malformations
The presence of heart defects

SYMPTOMATIC FRAMEWORK OF THE IATROGENIC FOCOMELIA

The iatrogenic phocomelia presents a slightly different symptomatological picture from that of the hereditary phocomelia.

The major difference lies in the fact that the iatrogenic form does not generally determine shorter or completely absent limbs.

As for the other clinical manifestations, they are particularly characteristic:

The tendency to develop facial paralysis
The anomalies and at the level of the ears and eyes; anomalies that lead to hearing loss and vision loss, respectively
Diseases of the gastrointestinal tract and the genitourinary tract.
The lack or incomplete development of one or both lungs
Defects of the digestive tract, heart and / or kidneys.

As observed at the time of marketing of thalidomide, about 40% of individuals with iatrogenic phocomelia die shortly after birth or in the first periods of life.

Diagnosis

Doctors can diagnose phocomelia in prenatal age, thanks to images of a simple ultrasound examination ( prenatal ultrasound ).

If for any reason the prenatal ultrasound has given a negative result despite the presence of the disease, the classic objective examination, to which all the new unborn babies are subjected to make sure of their health conditions, is sufficient to identify the condition.

If doubts persist or the doctor wishes to obtain an accurate description of the condition in place, genetic tests are available, which examine the DNA in detail and bring to light any anomaly. Among these genetic tests, there are also some that allow us to establish whether the phocomelia is of the hereditary type or of the iatrogenic type.

Treatment

Phocomelia is clearly an incurable disease, as the deformations and anatomical anomalies that characterize it are permanent.

Thanks to advances in medicine, however, the availability of orthopedic braces and prostheses is constantly increasing, allowing phocomelic patients to lead a higher quality life, compared to several decades ago.

Furthermore, for individuals with micrognathia, who present with language disorders, there is the possibility of subjecting them to therapies for language and for improving communication skills.

HEARING

Today, there are prostheses that replicate the upper and lower limbs with really important results.

Moreover, thanks to modern technology, medical engineers have created myo-electric prosthetic elements ( myoelectric prostheses ), which move using the energy provided by electric accumulators. Currently (October 2015), myoelectric prostheses are applicable only to the hand and arms; however, experts are studying new equipment for other parts of the body.

When to apply myoelectric prostheses?

The first myoelectric prostheses were implantable only in adults; the current ones, however, are also present in children, with enormous advantages for their scholastic growth and more.

Prognosis

Being an incurable disease, the phocomelia can never have a positive prognosis. However, thanks to current remedies, there is the possibility of curbing, even with good results, the drawbacks of the various anatomical anomalies, improving the quality of patients' existence.

Clearly, the extent of the improvement depends above all on how severe the symptoms induced by the phocomelia.