Treatment of chromosomal aberrations has been one of the major success stories of fetal precursor cell transplantation. They result from mutations that alter number of chromosomes or their structure.
Depending upon the type of stricken chromosome, location of damage caused by mutation, and its extent, chromosomal aberrations will present themselves in the phenotype.
When chromatin is lost or gained in the process of re-arrangement, it is said to be unbalanced. Unbalanced re-arrangements are generally associated with developmental delay or intellectual impairment, birth defects or nanism, whereas balanced re-arrangements often have no effect on physical or intellectual development.
Structural chromosome re-arrangements that are present at conception affect every cell and are called constitutional. Re-arrangements that occur during later development affect only a portion of cells and result in mosaicism. Structural re-arrangements that occur after birth are called acquired, and may cause cancer by altering cell cycle regulation.
Chromosomal abnormalities due to structural aberrations make up a significant portion of chromosomal genetic disease. At birth, structural re-arrangements, both balanced and unbalanced, were found in 1:400 of infants.
If a balanced structural re-arrangement is inherited there is a low risk for physical or mental impairment. However, when the abnormality is de novo, when parents have normal karyotypes, the risk for genetic disease is increased even when the re-arrangement is balanced.
In numerical aberrations the number of chromosomes differs from the normal diploid number of 46. Every human has a certain number of polyploid cells even under normal conditions, i.e. cells with doubled, tripled, or quadrupled number of chromosomes. The classical example are megakaryocytes. Some cells, i.e. thrombocytes, erythrocytes, squamous epithelial cells, have no nucleus, i.e. are nulliploid. Aneuploidia means decreased or increased number of chromosomes by 1 or 2.
Chromosomal aberrations are very frequent in humans, the younger the fetus, the higher the incidence. It is estimated that in aborted embryos or fetuses of the 1st trimester approximately 50% would be found with chromosomal aberrations, or that serious chromosomal aberrations would be encountered in 25% of all pregnancies. In very early spontaneous abortions the incidence of chromosomal aberrations is 60%, in non-live births 4 – 6 % and in live births 0.6.%. Fetuses with polyploidia, the most serious chromosomal aberration, are practically never born live, and if born live, they never survive. Overall incidence of chromosomal aberrations in live births is ~ 1.7%.
Medicine knows today syndromes of complete trisomy, partial trisomy or monosomy for each of 22 autosomal chromosomes, in some cases more that one. The overall incidence of autosomal chromosomal aberrations is 1:400 of live births.
Numerical chromosomal aberrations:
Abnormal number of autosomal chromosomes is the most frequent lethal factor, i.e. cause of the fetal death. Only the monosomies of chromosomes 21 and 22 have ever been born live of all possible complete monosomies. On the other side trisomies of chromosomes 7, 8, 9, 10, 13, 14,18, 21,22, were born live.
Number of types of sex-chromosome mosaicism is relatively large. Abnormalities are in numbers or structures. Incidence of serious sex-chromosome aberrations in live-born boys is 1:400, and in newborn girls 1:650.
A. Autosomal chromosomal aberrations:
Trisomy 21, Down syndrome or mongolism, is the most frequent and best known chromosomal disorder with incidence of 1:700 live births. It is a disorder of the whole body involving primarily abnormalities of physical and mental development with an added insult of marked weakness of the immune system:
1/ Somatic, gross motor, intellectual and mental development are lagging behind norms, and more so with each passing day after birth;
2/ Nanism, hypothyreoidism, and adrenal insufficiency, are the result of endocrine abnormalities;
3/ Dysproportionate growth of face and cranium, not noticeable at birth, becomes more obvious with age as a result of cranial growth delays; brain growth is slowed down dyspropotionately as well: occipital and parietal lobes lag behind more than the other parts, but actually the cerebellum is the most affected;
4/ Mongoloid physiognomy becomes more noticeable with age;
5/ Delayed development of all mesenchymal structures causes immune system deficiency;
6/ There is no direct relationship between the degree of visible chromosomal damage and the delay of intellectual development;
7/ Nanism begins in infancy but becomes most pronounced during puberty.
Typical clinical findings are psychomotor retardation, growth delay, muscle hypotonia, joint hypermobility, as well as brachycephalia with flat occiput, dysplastic auricles, wide, flat facies, mongoloid slant of eyes with epicanthus, and Bruschfield corneal spots, button nose with a wide root, open mouth with macroglossia and lingua scrotalis, gothic palate, dental anomalies, pectus carinatum, absence of ribs, congenital heart defects, umbilical hernia, gastrointestinal stenoses, short and wide fingers, brachymesophalangia and clinodactyly of little fingers, atypical dermatoglyphics.
There is an increased incidence of leukemias and immunological defects. At autopsy of adult Down syndrome patients morphological and histochemical changes typical of Alzheimer disease are found in the brain.
Lifespan is shortened, but in absence of congenital heart defects and serious immunological deficiencies Down syndrome patients can live up to 60 years of age.
There is no reproductive ability in complete trisomy 21, but patients with mosaic forms of trisomy 21 can be fertile and have normal offsprings.
The older the mother the higher is the incidence of trisomy 21 and all other chromosomal aberrations. [95, 185, 187, 197, 198, 235, 236, 237, 238, 239, 240]
1/ regulation of endocrine balance, in particular hypothyroidism and lowered function of glucocorticoid portion of adrenal cortex;
2/ elimination of ever increasing delay in brain development;
3/ correction of immune system deficiency;
4/ repair of defects of supportive tissues of the body;
5/ total rehabilitation of all body systems, by physiotherapy, active exercise, speech therapy, occupational therapy, and all educational toolds available;
6/ avoidance of therapeutic nihilism.
Correct nutrition, including yoghurt made by Acidophilus species, and mega-vitamin/mineral supplementation, are mandatory, in particular of vitamins A, B1 and B6. Enzymotherapy should be routinely used, in particular if the quality of nutrition lags.
Ultrafiltrates of animal fetal brain tissue should be given orally, or in suppositories, once a week between fetal cell transplantation treatments.
Majority of patients, with a suspicion of hypothyroidism, even though the laboratory tests of thyroid function are within limits of normal, have to receive minimal doses of thyroid hormone.
Depending upon the experience of the treating physicians, Down syndrome patients may be given Phosphatidylcholine, Choline bitartrate, or Centrophenoxine for neurotransmitter function augmentation. Piracetam has been shown to raise tryptophan levels in Down syndrome patients and the same applies to 5-hydroxytryptophan.
Since brain is the most damaged organ, fetal precursor cell transplantation treatment is begun with implantation of brain cortex, diencephalon, mesencephalon, hypothalamus. In the subsequent every 4 months repeated implantations, cell transplants of spinal cord, cerebellum, occipital lobe of brain, temporal lobe of brain, frontal lobe of brain, parietal lobe of brain, are selected as clinically necessary.
Besides fetal cell transplants of various parts of brain, also
cell transplants of thymus and adrenal cortex are advised for immune deficiency,
cell transplants of cartilage and placenta for achondroplasia-like condition,
cell transplants of thyroid and liver once between 6th and 10th year of age,
cell transplants of adrenal cortex and ovary to girls once between 6th and 10th year of life, cell transplants of adrenal cortex and testis to boys once between 8th and 10th year of life, cell transplants of cardiomyoblasts, liver, lung, for heart defects,
cell transplants of intestine, exocrine pancreas, liver, for gastrointestinal damage,
cell transplants of placenta, lens, corpus vitreum, for early cataract.
Standard medical textbooks state that genetic and chromosomal diseases have no known treatment, with rare exceptions. In reality there have been many publications from the university hospitals of Germany, U.S.S.R./Russia, Spain, and U.S.A. prior to 1957, etc. that report on the success in the treatment of many genetic and chromosomal diseases by a complex therapeutic protocol based on fetal precursor cell transplantation, so that therapeutic nihilism is not justified whatsoever.
Down syndrome has been a shining example. F. Schmid published data about his personal treatment of over 3, 000 children with Down syndrome, whereby 25% of his patients were able to attend regular schools.
Published data prove the statistically significant improvement in height, skull circumference, index of brain volume, IQ and mental development, motor development. Among untreated children with Down syndrome 50 – 60% dies during the first 5 years of life due to intercurrent infections and cardiac failure, while the mortality of children treated in accordance with the described protocol is the same as in normal children. Typical features of Down syndrome become less pronounced with each subsequent fetal precursor cell transplantation treatment and immune system deficiency is completely corrected.
In all such cases fetal cell transplantation has been carried out at an early age, or as soon as possible after the diagnosis was established. The earlier in life fetal precursor cell transplantation was carried out, the better was the outcome, while beyond certain age any such treatment was of questionable benefit: for example, to start fetal precursor cell transplantation for a child with Down syndrome beyond the age of 4 years was found to be of minor to minimal therapeutic benefit.
Our own published study of the first 83 patients with Down syndrome in which we evaluated mental and psychological functions showed the following.
The percentage of younger Down syndrome children (up to 3.5 years of age) with mental development index of over 50 points increased from 17% before the 1st SCT, to 58% after the 1st fetal cell transplantation, and to 71% after the 2nd FCT.
The IQ in the older children (4 - 9 years of age) moved after two fetal cell transplantations from the 25 to 49 points range to 50 - 69 points range, and the difference was statistically significant.
A decreased hyperactivity, improvement of impaired concentration, lessened stereotypia and behavioral inertia, and improved speech expressivity, were observed already after the 1st fetal cell transplantation, and the difference was statistically significant.
Volume of auditory/visual memory , productivity of thinking in categories, acoustic gnosis, and optic/spatial gnosis, were improved but not significantly.
After cell transplantation there was an improvement in motor area, particularly in fine coordinated movements, and in self-care habits, that were not psychometrically tested.
There was an absence of paroxysmal activity on EEG. 
Patients under 4 years of age were treated by human fetal transplantation of brain cortex, mesencephalon, diencephalon, parietal lobe of brain, while patients older than 4 years of age received also cell transplants of frontal lobe of brain, occipital lobe of brain.
After the publication of the report, the Down syndrome project in Moscow continued, and altogether 350 patients were treated.
Immune system deficiency of Down syndrome can be completely corrected. In our study of two age-matched groups of patients with Down syndrome carried out at the pediatric hospital in Moscow specialized in genetic and chromosomal aberrations, one group of 6 Down syndrome patients was treated every 6 months altogether three times by transplantation of human fetal cells of medulla alba of brain, brain cortex, and cerebellum, and the other group of 7 received implantation of saline. Height and weight, head circumference, psychological evaluation, laboratory tests: CBC, serum proteins, calcium, phosphorus, SGOT, SGPT, alkaline phosphatase, immunoglobulins, were measured. Already after 6 months, just before the 2nd cell transplantation, we had to re-evaluate the situation as 3 of 7 children in the control group were dead due to infections, while in the treated group all children were well. In the controlled group there was an increase of IgG and a marked decrease of IgA and IgM. In the treated group there was a mild decrease of IgG and an increase of IgA and IgM.
The decreases of IgA from 166 to 85, and IgM from 140 to 74, in the control group, were signs of immune system deficiency responsible for the death of 3 out of 7 infants, while the marked increase of IgG from 459 to 872 might have been an expression of recurrent infections.
The transplantation of human fetal cells apparently stimulated the immune system, as the levels of IgA increased from 68 to 83, and of IgM from 101 to 111, and that of IgG decreased from 551 to 463, which may be an indication of lesser frequency and severity of bacterial infections. A markedly improved immune system function in treated patients was a result of one treatment by fetal precursor cell transplantation only, and in that treatment only fetal cells of three parts of brain were implanted and no cells of immune system organs whatsoever. [144, 145]
Trisomy 13, or Patau syndrome, with incidence 1:4000-10000, is a highly lethal disorder with 86% of patients dying before reaching the 1st year of life. Psychic and somatic development is very retarded, there is marked failure to thrive, microcephaly and arhinencephaly, with anophthalmia, iris coloboma, dysplastic auricles, cleft lip and palate, as well as deafness, kidney anomalies, congenital heart defects, polydactyly, nail changes, abnormal dermatoglyphics.
Trisomy 18, or Edwards syndrome, with incidence 1:7500, four times more frequent in females, with substantially shortened lifespan. There is severe psychomotor retardation, dolichocephalia with bulging occiput and neck kyphosis, wide fontanelles and cranial sutures, dysplastic, low-placed auricles, hypertelorism with high eyebrows, micrognathia, short sternum, congenital heart defects, Meckel’s diverticulum, U-shaped kidneys, campodactylia, hip dysplasia, pes equinovarus, protruding calcaneus, abnormal dermatoglyphics, etc.
B/ Sex chromosome aberrations:
They are in comparison with autosomal chromosome aberrations more variable and much less dangerous to the patient’s life and health. Main phenotypic features are anomalies of external and internal genitalia and related defects of reproduction. The larger is the number of extra chromosomes X the more pronounced is mental retardation, i.e. patients with supernumerary chromosme X are frequently found among mentally retarded.
Monosomy X, or Turner syndrome, with incidence 1:4000 in live born girls, causes primary hypogonadism with gonadal dysgenesis, and from that resulting delayed puberty and primary amenorrhea, frequently also mental retardation, low stature, pterygium colli that has developed from cutis laxa, short neck with low hair line on nape of neck, low placed auricles, pectus carinatum with lateral placement of nipples, temporary congenital lymphedema of hands and feet, congenital anomalies of heart and large vessels, mainly coarctation of aorta and aortic stenosis, cubiti valgi, multiple pigmentary nevi, etc. Habitus is feminine. Estimated 99% of all conceptions with karyotype 45,XO are miscarried. Some Turner syndrome patients can get pregnant, but the outcome is usually unfavorable. Fetal precursor cell transplantation of ovary, placenta, adrenal cortex, pituitary, is recommended.
Our own experience with treatment of 9 years old patient with Turner’s syndrome, hypothyroidism, speech delay, with height 112.0 cm, weight 18.0 kgm, increased TSH, by cell transplantation of human fetal ovary, adrenal cortex, diencephalon, anterior lobe of pituitary, thyroid, was positive, as height increased 2 cm in 3 ½ months, weight 1 kgm, overall activity increased, speech cleared, appetite improved, TSH became normal. After the 2nd cell transplantation again the height increased by 2.0 cm within 4 months, weight another 1.0. kgm, and the overall impression was that of noticeable improvement. The patient was hospitalized at the Russian Research Center of Endocrine Diseases.
Noonan syndrome, 46,XY configuration, or male gonadal dysgenesis, with the same symptoms as Turner’s syndrome, infantilism, nanism, hypoplasia and dystopia of testis, lymphangiectastic edemas, no hair on the body, delayed bone development and skeletal abnormalities on hands. The findings become worse with age. Urinary 17-ketosteroids are decreased, the gonadotropin level is low. Treatment is by fetal cell transplantation of adrenal cortex, placenta, hypothalamus, testis, every 6 months, and additionally by cortisol, and gonadotropin.
Klinefelter syndrome, 47, XXY configuration, is relatively frequent chromosomal aberration in males with incidence 1:1000 of live born boys. Patients are tall, eunuchoid, with small, soft testicles, their secondary sex characteristics, i.e. facial hair, pubic hair, gynaecomastia, osteoporosis, varicose veins, are frequently more feminine than masculine, but the overall habitus is masculine. As a result of testicular dysgenesis there is azoospermia and infertility. These patients are frequently in psychiatric institutions. There is higher concentration of gonadotropins in urine, while levels of 17-ketosteroids are decreased.
Trisomy X, or XXX syndrome, with incidence of 1:1000 in live born girls. There is mental retardation , while malfunction of sex glands is present only in 49% of patients.
XYY syndrome with incidence 1:1000 in live born boys. There is tall stature, often mental retardation, and tendency toward aggressive behavior and criminal activity.
There are no reports of treatment of Intersex states by fetal precursor cell transplantations:
XY-female with sex reversal;
XX-male with sex reversal;
Swyer syndrome, in females with XY sex chromosome configuration, with gonadal dysgenesis and sexual infantilism;
Morris syndrome, or testicular feminization syndrome, or syndrome of androgen insensitivity, XR disorder, in females with karyotype XY;
Overzier syndrome, or agonadism, in females with XY configuration.
Structural chromosome aberrations:
Partial monosomy 5p-, or ‘cri du chat’ syndrome, with incidence 1:50000 to 1:100000, was so named because of a typical cry of infants resembling a cat. Children are born prematurely, are hypotrophic, with microcephaly, round moon facies, i.e. cranium is small, face is large, and hypertelorism, epicanthus, anti-mongoloid slant of eyes, gothic palate, mandibular hypoplasia, low placed auricles, and abnormal EEG. Fetal precursor cell transplantation of diencephalon, placenta, medulla alba of brain, and additional CNS cell transplants according to the dominant clinical findings, is advised.
Partial monosomy 4p-, or Wolf syndrome, with prenatal hypotrophy, microcephaly with severe CNS malfunction, frequent cranial asymmetry, cleft lip, skeletal deformities, dysmorphic U-shaped kidneys, hypoplasia of kidneys, congenital heart defects, abnormal genitals, fatal in childhood. Fetal precursor cell transplantation of thalamus, frontal lobe of brain, medulla alba of brain, temporal lobe of brain, mesencephalon, partietal lobe of brain, placenta, is recommended.
Deletion of long arm of chromosome 15, Willi Prader syndrome, or Angelmann syndrome, is treated by an implantation of fetal precursor cell transplants of hypothalamus, adrenal cortex, gonads, placenta. We treated in Italy a 6 years old female with a typical Angelmann syndrome, with mental retardation, speech delay, attacks of laugh, spasticity of extremities, and hypotonia of trunk, ataxia, one time only, but despite the positive response the parents did not continue with treatment, and were lost to a follow-up. When the treatment of genetic diseases starts too late, even though the parents are forewarned not to expect much, the results are seldom impressive.
Clinical protocol for treatment of genetic and chromosomal diseases by fetal precursor cell transplantation
1/ The diagnosis of the genetic, chromosomal or congenital diseases has to be as complete as possible.
2/ Any attempt to treat such patients by fetal precursor cell transplantation must be carried out immediately upon any suspicion that patient suffers from genetic or chromosomal disease and quick diagnostic confirmation. The later will the treatment begin, the lesser will be the success rate.
3/ Fetal precursor cell transplantation treatment has to be repeated at least every 3 - 4 months until no further improvement is observed. Any benefit of cell transplantation for impaired CNS function after the first 3 years of age is questionable.
4/ Treatment is a complex one, besides biological treatment it includes non-specific and specific metabolic stimulation, and rehabilitation measures. Partial treatment, i.e. omission of certain therapies recommended here, may be actually harmful in the long term. After the patient reached 4 years of age any such therapeutic errors cannot be corrected.
5/ It is virtually impossible to anticipate the success of fetal precursor cell transplantation for the treatment of genetic and chromosomal diseases. The crucial is the decision whether to continue with the treatment after the first fetal precursor cell transplantation. The decision to continue has to be made by parents and physicians together!
Clinical parameters to be followed in patients before and after fetal precursor cell transplantation, and the frequency:
General: once a month or as necessary:
i/ growth chart (height and weight, head circumference) every 3 months
ii/ measurement of body proportions once every 3 months
iii/ complete neurological examination once every 3 months
iv/ x-rays of skull every 6 months, and of chest as necessary
v/ CT scan or MRI of brain, and other organs, as necessary
vi/ total body x-rays
vii/ chromosomal evaluation
viii/ urine & blood enzyme studies for enzymopathies
ix/ blood & urine metabolic screen for aminoacids
x/ complete blood count, urinalysis
xi/ SMA 12
xii/ blood smear, reticulocyte count
xiii/ serum calcium, phosphorus and magnesium
xiv/ blood glucose, glucose tolerance test, if necessary
xv/ blood lead level
xvi/ prothrombin time, partial thromboplastin time
xvii/ blood clotting time, bleeding time, clot retraction time
xviii/ serum alkaline phosphatase
xix/ muscle enzymes: creatine kinase, LDH
xx/ serum iron and ferritin
xxi/ bone marrow examination
xxii/ cerebrospinal fluid examination
xxiii ultrasound of brain,liver, kidneys, and other organs
xxv/ TORCH screen (toxoplasmosis, rubella, cytomegalovirus, herpes)
xxvi/ urine culture for virus and other microorganisms
Only tests pertinent for the treated disease are to be carried out.
Immunological: once a month x3, then every 3 months:
i/ total lymphocytes
ii/ T-lymphocytes (CD3+)
iii/ T-helpers (CD4+)
iv/ T-suppressors (CD8+) and CD4/CD8
v/ NK (CD16)
vi/ B-lymphocytes (CD22 and CD19)
vii/ serum IGG, IGA, IGM
viii/ serum complement (CH50)
Special: once every 4 months or as clinically indicated, choice of tests according to diagnosis:
i/ intravenous pyelogram
iii/ urine electrophoresis
iv/ 24 hour urine for sodium
v/ 24 hour urine for phosphorus
vi/ urinary 17-ketosteroids, 17 hydroxysteroids, pregnanetriol, 17-hydroxyprogesterone
vii/ serum renin level
viii/ EEG if necessary
ix/ ophthalmological examination if necessary
x/ blood & urine for galactose and fructose
xi/ biopsy of liver, gonads, muscles, lymphnodes, spleen aspiration for enzymes
xiii/ hemoglobin electrophoresis
xiv/ plasma von Willebrand factor, level of factor VIII and IX
xv/ stool for trypsin and chymotrypsin, and fat content
xvii/ quantitative pilocarpine iontophoresis sweat test
xviii/ plasma level of phenylalanin and tyrosine
xix/ water deprivation test
xx/ urinary mucopolysacharides
xxi/ dystrophin by immunoblotting
xxiii/ nerve conduction velocity
Only tests pertinent to the treated disease are to be done.
Freqency of office visits: 4 weeks and 48 hours before fetal precursor cell transplantation,
24 hours after and then once a week for the first month after fetal precursor cell transplantation, once a month thereafter.
K.U., a white female, born November 1989, with a Down syndrome, was treated by Prof.Dr. F. Schmid by cell therapy at the age of 12 months, and started to follow his protocol of supportive treatment, which included homeopathic doses of thyroid extract, Cerebrolysin, and multivitamins/minerals, besides various forms of rehabilitation.
The patient did not have any congenital heart or gastrointestinal disease, nor any thyroid abnormalities. Her hearing and vision appeared normal.
The cell therapy was repeated one year later.
With the recommendation of F. Schmid this patient was on March 10, 1993, treated by our team by human fetal cell transplantation in Moscow, in front the cameras of ‘CBS 60 Minutes’. The parents of this patient and we were too naive to trust the unscrupulous ‘CBS 60 Minutes’ staff. We, the patient and her parents, were betrayed and grossly abused by Mike Wallace. Responses of the patient’s parents and ours to one question were pasted to completely different question, and the whole matter of treatment of Down syndrome by fetal cell transplantation was misrepresented and ridiculed.
The next treatment of this patient by fetal cell transplantation was carried out by our team in Moscow in March 1994. Besides physical and neurological examinations, and necessary laboratory tests, prior to this treatment the patient underwent an evaluation by our pediatric clinical psychologist. (This was unfortunately not done in March 1993 due to all trouble with CBS 60 Minutes.) The patient’s IQ was 63. The baseline levels of impairment of various parameters, such as hyperactivity, concentration, behavioral inertia and stereotypia, expressive speech, articulation, auditory / verbal memory, optic / spatial gnosis, acoustic gnosis, categorical thinking, were established, while recognizing that this patient had had quite competent treatment already, thus these were not true ‘baseline’ data. Another difficulty was the language barrier.
In March 1995 this patient was treated by F. Schmid by zellentherapie..
Subsequently the patient underwent a psychological evaluation by a U.S. pediatric psychologist, and parents showed us the report when in April 1996 they brought their daughter to Moscow for the next fetal cell transplantation. The psychologist did not find any significant abnormalities, and did not realize that their daughter had Down syndrome, as the parents told us with great excitement.
Prior to her treatment of April 1996 the patient underwent another evaluation by our pediatric clinical psychologist. IQ was 78. Hyperactivity, concentration, behavioral inertia, expressive speech, articulation, were significantly improved. Auditory/verbal memory, optic/spatial gnosis, acoustic gnosis, categorical thinking, were improved as well, but not to a significant degree. Fine coordinated actions were significantly improved, as well as self-care habits.
All these years the protocol of supportive therapy of F. Schmid was followed as well.
Note: Cell transplantation was continued by the parents of this patient despite all of the media attacks, and sensation seeking, because they recognized the benefit of this treatment for the improvement of the condition of their daughter. At the age of 6 hardly anyone could somatically recognize that this girl had a Down syndrome. Actually she was very attractive. She was attending regular school and able to scholastically compete with other children. Her only real deficiency was in the area of abstract thinking. Her vocabulary was below the level of her classmates, and one could expect difficulty in mathematics in the future.
No one could tell these parents that Down syndrome cannot be succesfully treated.