Cholelithiasis in Down's syndrome.

Cholelithiasis is considered uncommon in infancy, childhood, and adolescence. We performed a prospective, controlled study showing that children with Down's syndrome have a significantly higher prevalence of cholelithiasis (4.7%) compared with controls (0.2%). Clinicians should be aware of the risk of gallstones in children with Down's syndrome.     

Defective antibody response to bacteriophage phichi 174 in Down syndrome.

Antibody responses to bacteriophage phichi 174 were studied in 17 institutionalized patients with trisomy 21 and in six mentally retarded control patients with normal karyotype. Primary antibody response was significantly impaired in 11 of the 17 patients. Secondary immune response was normal in one, moderately impaired in seven, and very low in nine patients. Tertiary immunization further differentiated the two groups: those with moderately impaired secondary immune responses developed normal serum titers of predominantly IgG antibody; patients with low secondary immune responses had extemely impaired tertiary immune responses consisting mainly of serum IgM antibody.     

Down's syndrome and acute lymphoblastic leukaemia: clinical features and response to treatment.

AIMS: To examine the clinical and biological features of acute lymphoblastic leukaemia in children with Down's syndrome (DS), to compare their survival with other children, and to determine if entry to trials and survival has improved. METHODS: Examination of presenting features and response to treatment in patients treated in two consecutive national trials, MRC UKALL X and XI. RESULTS: The proportion of children with DS was significantly higher in UKALL XI (1.9%) than UKALL X (0.9%). Children with DS tended to be under 10 years and to have the common ALL subtype. Cytogenetic analysis showed that favourable features, such as high hyperdiploidy and t(12;21) were less frequent but also that there was a lack of translocations associated with a poor prognosis. Children with DS showed no increase in risk of relapse at any site but their survival and event free survival were inferior to other children. These results were caused by an increased number of infective deaths during remission (11% compared to 2%). At five years overall survival was 73% in DS children compared with 82% in other children; event free survival was 53% compared to 63% in non-DS children. CONCLUSIONS: Entry of children with DS to national trials has increased and survival has improved. However they remain at risk of relapse and also of treatment related mortality. These findings emphasise the need for both intensive chemotherapy and optimal supportive care.     

Thyroid dysfunction in Down's syndrome.

One hundred and sixteen children with Down''s syndrome, living in the community, were examined for clinical or laboratory evidence of thyroid dysfunction. Three were hypothyroid and one was hyperthyroid. Twenty eight (29%) had thyroid autoantibodies. Autoimmune conditions were present in first or second degree relatives of 35 (30%) of the children, and in 17 (15%) this was a thyroid disorder. The families of normal control children also showed a 30% incidence of overt autoimmune conditions, and 19 (16%) families showed overt thyroid disease.     

Thymic deficiency in Down's syndrome.

Children with Down's syndrome (DS) often have small and abnormal thymuses, with lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation--a picture resembling thymic involution. Besides this, they have markedly enlarged Hassall's corpuscles, some surrounded by a sheath of lymphocytes. Patients with DS are known to have increased numbers of respiratory infections; they also have a higher incidence of lymphatic leukemia than do individuals who do not have DS. Studies of cell-mediated (thymic-dependent) immunity demonstrate that children with DS have both diminished numbers of T cells as well as functional deficiency of these cells.     

Growth of children with Down's syndrome: birth to age 3 years.

A sample of 90 children with Down's syndrome were measured for recumbent length and weight from birth to age 36 months at the Children's Hospital Medical Center in Boston. At birth, means for both length and weight were reduced by about 0.5 SDs from the control group means. By 36 months, mean recumbent length was greater than 2 SDs below that for the control group, while the mean for weight was reduced by about 1.5 SDs from the control group mean. Growth velocity for both length and weight was most deficient within the first two years of life. About 30% of the sample demonstrated excess weight for length relations by 36 months. Children with moderate or severe heart disease were significantly smaller than those without or with mild cardiac problems at all times after birth. Measurements of a subsample of children at 4, 5, and 6 years of age suggested that growth velocity after 3 years of age may be within the range of normal. Assessment of growth of the child with Down's syndrome may be carried out with reference to charts plotting tenth to 90th percentiles based on these data.     

Craniovertebral abnormalities in Down's syndrome.

The ligamentous laxity associated with atlantoaxial subluxation has been assumed as a normal occurrence in 15-20% of Down's syndrome patients. The occipitoatlantoaxial instability that accompanies this entity has been poorly recognized. The medical records and radiographic findings of 18 symptomatic patients with Down's syndrome and cervicomedullary compromise were reviewed (1979-1991). All patients were evaluated prospectively under protocol for abnormalities of the cranial vertebral junction. There were 11 males and 7 females (age 3-42). 'Fixed' atlantoaxial luxation was seen in 8 (5 developed precipitous onset of cervical medullary compression). Occipitoatlantoaxial instability was present in 9 and associated rotary luxation in 9. The average predental space was 8 mm in the neutral position in 18 individuals. Two adolescents had previously undergone atlantoaxial dorsal fusion with subsequent progressive basilar invagination due to unrecognized occipitoatlantal instability. An os odontoideum was seen in 3 patients. Irreducible invagination in 2 was treated with anterior decompression followed by dorsal occipital cervical fixation. The occipital cervical fixation was utilized in 10 individuals. Atlantoaxial dorsal fusion was made in 7 and 2 patients with acute rotary luxation of C1 and C2 were treated with immobilization. Halo immobilization in two individuals following a dorsal occipital cervical fixation produced an anterior fusion at the cranial vertebral complex indicating active vertebral ligamentous pathology. The review focuses on increased incidence of occiput cervical instability in the spectrum of craniovertebral junction abnormalities associated with Down's syndrome. A large percentage has an odontoid ossicle probably as a result of repeated minor trauma. The results of surgical stabilization have been shown to be excellent.     

Bacterial tracheitis in Down's syndrome.

Four children with Down''s syndrome and bacterial tracheitis are described. In three the infection was due to Haemophilus influenza. In patients with Down''s syndrome presenting with stridor tracheitis should be considered and appropriate treatment started.     

T lymphocytes apoptosis and mitochondrial membrane potential in Down's syndrome

The increased susceptibility to infection, malignancies, and autoimmune disease, suggest that immunodeficiency is an integral part of Down's syndrome (DS). Little is known about the mitochondrial damage and tendency to apoptosis in peripheral T lymphocyte cells in DS. We studied 30 children with DS and 30 normal children, 15 of each group having no evidence of acute infection and 15 with acute infection. Potential apoptosis and membrane mitochondrial potential (MMP) were measured by flow cytometry. T lymphocytes in peripheral blood from DS patients do not display an increased tendency to undergo apoptosis, although a significant loss of MMP was found.     

Mortality and life-table in Down's syndrome.

The causes of death in 130 patients with Down's Syndrome and mortality rates from a material of 524 patients were tabulated; a life-table for the ages over 5 years was constructed. An overall death rate of 5-7 times the general population rate was found. No sex difference was observed. The excess mortality was expecially high for heart disease and respiratory disease. Also infectious diseases, others than pneumonia and tuberculosis, showed high mortality rates.     

Amino acid profile in Down's syndrome.

Fasting plasma and urinary amino acid concentrations were studied under carefully controlled conditions in 22 children with Down''s syndrome and in age matched controls. The only significant difference between the groups was a higher mean plasma lysine concentration in Down''s syndrome patients compared to controls.     

Down's syndrome and acute lymphoblastic leukaemia: clinical features and response to treatment

AIMS—To examine the clinical and biological features of acute lymphoblastic leukaemia in children with Down''s syndrome (DS), to compare their survival with other children, and to determine if entry to trials and survival has improved.METHODS—Examination of presenting features and response to treatment in patients treated in two consecutive national trials, MRC UKALL X and XI.RESULTS—The proportion of children with DS was significantly higher in UKALL XI (1.9%) than UKALL X (0.9%). Children with DS tended to be under 10 years and to have the common ALL subtype. Cytogenetic analysis showed that favourable features, such as high hyperdiploidy and t(12;21) were less frequent but also that there was a lack of translocations associated with a poor prognosis. Children with DS showed no increase in risk of relapse at any site but their survival and event free survival were inferior to other children. These results were caused by an increased number of infective deaths during remission (11% compared to 2%). At five years overall survival was 73% in DS children compared with 82% in other children; event free survival was 53% compared to 63% in non-DS children.CONCLUSIONS—Entry of children with DS to national trials has increased and survival has improved. However they remain at risk of relapse and also of treatment related mortality. These findings emphasise the need for both intensive chemotherapy and optimal supportive care.     

Growth and somatomedin responses to growth hormone in Down's syndrome.

Five growth retarded children with Down''s syndrome, three girls and two boys aged between 3 1/2 and 6 1/2 years with trisomy 21, were treated with human growth hormone for six months. Before treatment the growth hormone response to sleep and insulin-arginine load, as well as serum concentrations of insulin, thyroid hormones, and cortisol was found to be in the normal range. During the treatment with human growth hormone the growth velocity increased in all the children with Down''s syndrome from 2.3-2.8 cm to 3.3-5.8 cm per six months. The serum concentrations of immunoreactive insulin like growth factor 1 (IGF-1) were low before treatment and increased during the treatment with human growth hormone. The serum concentrations of immunoreactive insulin like growth factor 2 (IGF-2), which were within the normal range, however, increased during treatment with human growth hormone. Children with Down''s syndrome respond to treatment with human growth hormone, with an increase in both growth velocity and serum somatomedin concentrations.     

Benefits to Down's syndrome children through training their mothers.

This study investigated the hypothesis that training of mothers with Down's syndrome children would be beneficial both to the child and parents. The mothers were taught behaviour modification techniques based on learning theory and were given group discussions on dealing with their family or personal problems. The subjects were 16 mothers with a Down's syndrome child, divided into two groups on the basis of their child's sex and chronological and mental ages. The Griffiths Scale was used for assessment. The mothers in the treatment group received 12 sessions of training and group counseling over a 6-month period, whereas the control mothers received no additional attention except the usual routine from the general practitioner and health visitor. The result show clear gains to both the child and mother in the treatment group. The child improved, especially in language development as well as in the other areas, and the mother-gained more confidence and competence in her daily management of the child.