Deaf Mutism Research Articles

Human iodine requirements determined by the saturation kinetics model

Iodine plays a decisive role in metabolism and the process of early growth and development of most organs, especially of the brain. Effects of iodine deficiency include goiter, stillbirth and miscarriage, neonatal and juvenile thyroid deficiency, dwarfism, mental defects, deaf mutism, spastic weakness and paralysis. In this study, the application of a mathematical model (derived from Machaelis-Menten enzyme kinetics) to iodine measured in urine samples from a randomly selected group derived from the Egyptian village of West El-Mawhoub in the Dakhlah Oasis resulted in the conclusion that iodine excretion parameters can be used to characterize iodine utilization and accurately predict the level of salt iodination required to maintain proper physiological functions. The four parameter saturation kinetics model analysis indicated that a salt iodination level of 63 mg/kg reduced the severity of IDD, with 83% of the studied subjects having urinary excretion levels of 1.18 μmol/L. This gives a convenient mechanism for providing adequate dietary iodine with a non-invasive index for the avoidance of IDD. Commercially available salt was analyzed using standard iodiometric titration methods to determine iodination levels. Analysis revealed that only 20% of the commercially available salt complied with the manufacturer’s label and revealed the presence of large individual variability between batches amounting to −95 to +150% of the claimed iodine level. Therefore, salt iodination requires careful supervision to ensure that promised iodine levels are being delivered and consumed.

Iodine and Neuropsychological Development

The establishment of the essential link among iodine deficiency, thyroid function and brain development has emerged from a fascinating combination of clinical, epidemiologic and experimental studies. The central human phenomenon that focuses this relationship is the condition of endemic cretinism, described from the Middle Ages and characterized in its fully developed form by severe brain damage, deaf mutism and a spastic state of the hands and feet. The demonstration of the prevention of cretinism in a double-blind controlled trial with injections of iodized oil in Papua New Guinea (1966-1970) established the causal role of iodine deficiency in cretinism by an effect on the developing fetal brain. Cretinism could not be prevented unless the iodized oil was given before pregnancy. Iodine deficiency is now regarded by the WHO as the most common preventable cause of brain damage in the world today, with at least 30 million suffering from this preventable condition. Since 1986 the international NGO, the International Council for Control of Iodine Deficiency Disorders, has worked closely as an expert group with WHO and UNICEF in assisting countries with a program of universal salt iodization for the elimination of iodine deficiency as a cause of brain damage by the year 2000. In 1996, WHO reported that 56% of the population of 83 developing countries now had adequate access to iodized salt. This represents an increase of 750 million since 1990 with protection of 12 million children.

A case of deaf–mutism as an expression of pure word deafness: neuroimaging and electrophysiological data

We report a case of pure word deafness, clinically expressed as deaf-mutism in a 17-year-old girl, who was affected from encephalitis when she was 18 months old and hadn't acquired language skills. Actually, physical examination revealed buccolingual apraxia and absence of spontaneous speech, auditory comprehension, repetition and denomination, whereas perception of non-verbal sounds was preserved. The seven waves of brainstem auditory evoked responses (BAER) were present with normal latencies; middle latency responses (MLR) were also normal. Magnetic resonance imaging (MRI) showed bilateral temporoparietal lesions. This case proves that lesions which may give rise to word deafness, when they occur in prelingual age, can determine a peculiar deafmutism clinical picture.

Prevalence and pattern of major neurological disorders in rural Kashmir (India) in 1986.

In 1986 in the Kuthar Valley in the Anantnag District of south Kashmir (northwestern India), we studied the population to ascertain the prevalence and pattern of various neurological diseases. A house-to-house survey was done in a rural population of 63,645 (according to a World Health Organization protocol, 1981). 616 cases of major neurological disorders were detected, yielding a prevalence of ratio of 9.67/1,000 as of prevalence day November 1, 1986. The prevalence ratios for various common neurological disorders were: epilepsy 2.47/1,000; stroke 1.43/1,000; paralytic poliomyelitis 2.18/1,000; mental retardation 2.09/1,000; deaf mutism 1.63/1,000, and cerebral palsy 1.24/1,000. Persons with these conditions constituted 92% of all neurological cases. Patients with motor neuron disease, Alzheimer's dementia or multiple sclerosis were not found.

Clinical pattern and the genetics of the fetal iodine deficiency disorder (endemic cretinism): Results of a field study in Highland Ecuador

The clinical manifestations of various degrees of mental retardation, spastic diplegia, and deaf mutism are known as the neurologic type of endemic cretinism (EC), occurring in countries with high goiter endemicity. Maternal iodine deficiency has been established as the major cause in EC, whereas a genetic predisposition has not been well-documented. Genetic data on 70 families with EC from Highland Ecuador are reported. A segregation analysis of 49 fully classified families yielded an estimate of P = 0.245 (var [P] = 0.00167). Half-sibs were all unaffected and no significant birth order effect was observed among 101 probands. The data indicate an autosomal recessive predisposition as a major etiological factor. Because the neurologic type of EC represents a defined section of the spectrum of iodine deficiency disorders (IDD), the term fetal iodine deficiency disorder (FIDD) rather than cretinism is suggested. The clinical findings in 70 patients were used to delineate the minimal diagnostic criteria of FIDD.

The brain in iodine deficiency.

Global descriptive, epidemiological studies have established the relation of iodine deficiency to endemic cretinism which, in its fully developed form, is characterized by mental deficiency, deaf mutism and spastic diplegia. However, a second less common variant--myxedematous or hypothyroid cretinism--is characterized by severe hypothyroidism with dwarfism. Mixed forms occur. It has been shown that both conditions can be prevented by correction of the iodine deficiency before pregnancy. Cretinism and development--now termed iodine deficiency disorders (IDD). A number of recently developed animal models establish the effect of severe iodine deficiency on brain development. These include the rat, the marmoset monkey and the sheep. These models are all characterized by the production of severe maternal and fetal hypothyroidism which is associated with effects on the maturation of the cerebral cortex and cerebellum. There was a reduced brain weight with a reduced number of cells as indicated by reduced DNA, a greater density of cells in the cerebral cortex and reduced cell acquisition in the cerebellum. Studies of the mechanisms involved have been carried out in the sheep. The findings reveal significant, though less severe, effects of fetal thyroidectomy (late gestation) and a significant effect of maternal thyroidectomy on brain development in mid-gestation. A combination of maternal and fetal thyroidectomy has similar but more severe effects than iodine deficiency. In the light of current knowledge of the embryology of the brain it is suggested that the critical time for the effect of iodine deficiency is the mid-trimester (14-18 weeks) when the neurons of the cerebral cortex and basal ganglia are formed and could be damaged by the effect of iodine deficiency on maternal thyroid function. There is now recent evidence indicating transfer of maternal thyroxine across the placental barrier early in pregnancy. In this way, neurological cretinism might be produced. Impaired fetal thyroid function would follow in the third trimester and augment the effect of reduced maternal thyroid function. Impaired fetal thyroid function alone could produce the hypothyroid form of cretinism. Further experimental studies, particularly into the postnatal period, are required to substantiate these suggestions. Apart from this, further study of the effects of iodine deficiency on brain development at the subcellular and cellular levels are likely to be most productive.

Prevalence and genetic aspects of deaf mutism in Shanghai.

Two hundred and eighty-five cases of congenital deaf mutism were ascertained in a population of 483,611 in Zhabei District in Shanghai. The prevalence was 0.059% (1:1697). Inherited cases accounted for...

Iodine deficiency disorders (IDD) and their eradication.

Disorders resulting from severe iodine deficiency affect more than 400 million people in Asia alone. These disorders include stillbirths, abortions, and congenital anomalies; endemic cretinism, characterised most commonly by mental deficiency, deaf mutism, and spastic diplegia and lesser degrees of neurological defect related to fetal iodine deficiency; and impaired mental function in children and adults with goitre associated with subnormal concentrations of circulating thyroxine. Use of the term iodine deficiency disorders, instead of "goitre", would help to bridge the serious gap between knowledge and its application. Iodised salt and iodised oil (by injection or by mouth) are suitable for the correction of iodine deficiency on a mass scale. A single dose of iodised oil can correct severe iodine deficiency for 3-5 years. Iodised oil offers a satisfactory immediate measure for primary care services until an iodised salt programme can be implemented. The complete eradication of iodine deficiency is therefore feasible within 5-10 years.

Patients with long Q-T syndrome: A caveat for the oral surgeon

Three children with long Q-T syndrome were admitted to the hospital for elective minor oral surgery. Patients afflicted with this syndrome often have a family history of recurrent syncope, prolongation of the Q-T interval on the electrocardiogram, sometimes deaf mutism, and occasionally sudden death. Their cardiac dysrhythmias are controlled by a variety of medications, all of which must be understood before the oral surgical procedure is undertaken, so that potentially lethal events can be recognized and dealt with appropriately. The management of two of the three patients was further complicated by juvenile-onset diabetes mellitus.

Genetic and Clinical Findings in Fifty-Two Cases of Bardet-Biedl Syndrome in 23 Families

A systematic clinical and psychiatric examination of MR patients at NIMHANS led to the diagnoses of 44 cases of BB Syndrome in 23 families of which 8 had died during infancy. Family history revealed 8 more similar cases in their relatives of which 5 had died. 1 Consanguinity was noted in 80% of the families. Psychoses, deaf mutism and simian crease were some of the associated clinical features in these cases.

Auditory Training for Deaf Mutism and Acquired Deafness (1895).

Auditory Training for Deaf Mutism and Acquired Deafness (1895).

Endemic goitre in India: prevalence, etiology, attendant disabilities and control measures.

Endemic goitre due to iodine deficiency is a health problem that afflicts, with varying degrees, of severity, an estimated 40 million people throughout the subcontinent. In areas where goitre prevalence is high (more than 50%) major attendant disabilities of endemic goitre such as endemic cretinism, deaf—mutism and feeble mindedness are present in about 4% of the population. Iodisation of salt can be an effective prophylactic measure against goitre. Though, a National Goitre Control Programme was launched 2 decades back, only less than 15% of the known goitrous areas have been covered by the programme (1979–80). The major constraints in this regard seem to be inadequate availability of iodised salt. Urgent implementation of iodine prophylaxis is imperative. Also, the benefits of modern technological advancement for early detection and prompt treatment of thyroid related developmental abnormalities of the brain among the new borns in these areas, should be utilised as an interim measure to prevent further such damages.

Thyroid function, iodine nutrition and fetal brain development.

SUMMARYThe clinical effects of congenital hypothyroidism on brain function have been well documented and the need for early diagnosis and treatment established. This is now possible through neonatal screening. Improved results may be expected but there is evidence of prenatal effects. More evidence of the effects of fetal hypothyroidism on brain development is required in order to determine the need for antenatal diagnosis. Experimental studies indicate significant effects of hypothyroidism on fetal brain development in the monkey and the sheep during the third trimester. In the rat, significant effects, particularly on the cerebellum, can be shown in the first 3 weeks postnatally, a period corresponding to the third trimester of the human pregnancy. Retardation of cerebellar nerve cell migration, differentiation, growth and arborization have all been demonstrated, together with persistence of the external granular zone and DNA polymerase activity. Such effects provide an explanation for the common occurrence of ataxia and nystagmus in congenital hypothyroidism. Severe iodine deficiency with an intake less than 20 μg per day and high goitre prevalence in endemic goitre areas is associated with the condition of endemic cretinism characterised in its fully developed form by mental deficiency, deaf mutism, spastic diplegia and squint with absence of clinical hypothyroidism. This condition does not respond to replacement therapy with thyroid hormones. Correction of the iodine deficiency prior to pregnancy will prevent the condition, but correction of the iodine deficiency in the latter half of pregnancy will not. This indicates the necessity of iodine for fetal brain development in man. Experimental studies in the guinea pig and sheep indicate an effect of severe iodine deficiency on brain growth early in pregnancy at the time of neuroblast multiplication. Such an early effect could provide an explanation for the irreversibility of the effects of severe iodine deficiency on brain development in man. The role of maternal and fetal hypothyroidism and iodine deficiency itself in these effects has still to be defined. It may be concluded that the relation

Goiter and Deaf Mutism

The occurrence of deaf-mutism and goiter unassocaited with creatinism or mental retardation in euthyroid patients is known as Pendred's Syndrome. It is considered due to a single mutant recessive gene responsible for both the goiter and deafness. The penetrance is high, the intenseness of expressivity may vary within the same family and only one generation is affected. The extremely atypical hyperplasia seen in such goiters has been considered malignant. In 1956 the author reported a family in which 4 of 6 sibilings demonstrated Pendred's Syndrome. Three of the 4 had undergone thyroidectomy, two were considered to have carcinoma. Nineteen years later the family is again reported. The fourth sibling has recently undergone thyroidectomy. This thyroid demonstrated the same atypical hyperplasia as seen in the elder two siblings. The 19 year followup of this family has shown no evidence of recurrence or metastases, indicating that the atypical hyperplasia is probably not malignant. Pendred's Syndrome is described and certain suggestions are made for the counseling of the parents and the treatment and counseling of those children so afflicted.

Pituitary-thyroid function in Pendred's syndrome.

Pendred's syndrome is reported in three siblings. All were euthyroid, with large goitres and deaf mutism and all had an unusual deposition of pigment in the retina. All had raised circulating levels of triiodothyronine (T-3) and an exaggerated response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). It appears that their compensated euthyroid state was maintained by the raised T-3 levels. We suggest that preferential T-3 production is maintained by increased TSH secretion in subjects with intrathyroidal iodine deficiency secondary to thyroid organification defect.

Kartagener's syndrome and deaf-mutism: an unusual association.

Two of three siblings with deaf mutism in a Negro family had complete Kartagener's syndrome. This association has not been reported before. Kartagener's syndrome is rare in the Negro race.

Studies of a sibship with apparent hereditary resistance to the intracellular action of thyroid hormone

Further studies are presented on a previously described sibship 1 with a familial syndrome combining deaf mutism, delayed bone maturition, stippled epiphyses, goiter, and high levels of circulating thyroid hormone in the presence of euthyroid clinical state. Seventy-five to 90% of the circulating iodinated compounds were L-thyroxine and L-triiodothyronine by chromatography, ability to bind to thyroxine-binding globulin, L-amino acid oxidase digestion, and precipitation to constant specific activity. The usual basic laboratory tests were normal, and there was no direct evidence of endocrine disease other than that of the thyroid. Although all standard tests of thyroid function, with the exception of the basal metabolic rate (BMR), were typically those of hyperthyroidism, the patients appeared clinically euthyroid. This diagnosis is supported by the normal BMR, serum lipids, cholesterol, tyrosine, enzymes and albumin metabolism, and by normal caloric intake, dentition, and steady growth. Certain tissues appeared to be resistant to thyroid hormone action. We observed delayed bone age, epiphyseal stippling, and low hydroxyproline excretion. Sensorineural deafness, congenital nystagmus, elevated serum carotene, and possibly metachromasia in the cultured skin fibroblasts were also suggestive of hypothyroidism. Endogenous pituitary thyrotropin secretion was not completely suppresed by the high, blood hormone level. Administration of 1 mg/day L-T 4 or 375 μg/day L-T 3 produced some effect on connective tissues. Thyroid gland activity was only partially suppressed with such treatment. Administration of the acetic acid analogue of triiodothyronine had no effect other than thyroid gland suppression, attributed to the liberation of large amounts of iodine. β-Adrenergic blockage and 45 days of propylthiouracil therapy also failed to produce detectable effects. Labeled thyroxine and triiodothyronine studies indicate that these hormones penetrate the liver and other tissues normally or even at an excess rate and are degrated three- to five fold more rapidly than normal. Progressive amelioration of the syndrome has been noted over the past 6–7 yr. The etiology of this syndrome remains unclear. It appears to date to be a congenital. inherited metabolic and possibly transient defect associated with variable degrees of intracellular resistance to the action of thyroid hormone, which has been partially compensated by excess hormone production.

Inner ear pathology in deafness due to maternal rubella.

BETWEEN THE YEARS 1939 and 1941 an epidemic of rubella swept Australia and Tasmania. The first to recognize the teratogenic effects of maternal rubella as a cause of fetal abnormalities was Gregg in 1941. Shortly thereafter in 1943 Swan and his colleagues,¹described deaf mutism as one of the more frequently occurring anomalies in prenatal rubella. A multitude of clinical studies have followed and numerous clinical cases of deafness have been well documented. The recent epidemic that spread across the United States during the years 1963, 1964, and 1965 brought a renewed interest in the general problem and undoubtedly will provide additional temporal bones for histopathological study. There have been several reports of clinical pathological studies of the temporal bones from fetus and from infants, but the majority of these were normal. There remains a sparsity of documented cases of deafness with clinical and pathological correlative studies. Even in

CLINICAL OBSERVATIONS ON CHILDREN WITH RETARDED SPEECH

The problems of children with retarded speech have been noticed by many clinicians such as iatrists and psychologists. tions on 466 delayed language cases who visited the hearing and speech clinic for children in E.N.T. Department of Tokyo University Hospital since 1960 to 1962. Subjects are classified into following groups nce) der 84 of IQ) 3) mutism due to hearing disturbance deaf mutism(threshold is over 61 dB) Investigations are made on method of diagnosis, evaluation of speech ability, etiology and treatment. The informations obtained from parents are ation is necessary for correct evaluation of speech and hearing ability. Sixty per cent of the cases are boys and fourty per cent are girls, and most of them(70 per cent) are under 4 years of age. The further classification and investigation can be performed in accordance with correct evaluation of speech ability. Poor nurseing environment and brain damages followed by abnormal progress of pregnancy and delivery, especially asphyxia, are considered to be significant as the causes of audimutitas. On the mentally retarded cases, hereditary pre. dispositions such as mental retardation, neurosis and intermarriage are prominently noted. Clinically, a group of slight deafness is not adequate because 8 per cent of them revealed profile of the audimutitas and another 26 per cent have mental deficiency.Causes of slight deafness is not clear. Hereditary predispositions(impaired hearing, intermarriage and neurosis), disturbance of pregna ncy, abnormal delivery, childrens disease with higi fever are considerable factors as the cause of dea mutism and medium deafness. Patients were treated medically by γ-aminobu tilic acid and others, and given education by speed therapy.Group therapy for audimutitas childrei is markedly effective and attention to early con mencement of therapy should be paid.

Partial albinism and deaf-mutism due to a recessive sex-linked gene.

Several forms of partial albinism as well as of congenital perceptive deafness are known to be inherited. Conditions in which there is association of the two, like the Waardenburg-Klein syndrome, are associated also with other defects and are inherited as autosomal traits. 1,2 This paper presents clinical, genetic, and laboratory investigations of a family in which all affected members were afflicted with both partial albinism and deaf mutism, with no other detectable defects. Moreover, this rare condition appears to be due to a single recessive gene located on the X-chromosome. The Pedigree (Fig. 1) comprises 6 generations of a Jewish Sephardi family of Moroccan origin, living until recent years in Alexandria, Egypt. Fourteen members of the family, of generations III, IV, and V, were affected. Seven of them are alive and five of them live in Israel. All the affected individuals were males. Clinical Syndrome and Laboratory Findings The major