Intrinsic abnormalities of lymphocyte counts in children with down syndrome

OBJECTIVE: Down syndrome (DS) is associated with an increased frequency of infections, hematologic malignancies, and autoimmune diseases, suggesting that immunodeficiency is an integral part of DS that contributes significantly to the observed increased morbidity and mortality. We determined the absolute counts of the main lymphocyte populations in a large group of DS children to gain further insight into this immunodeficiency. STUDY DESIGN: In a large group of children with DS (n = 96), the absolute numbers of the main lymphocyte subpopulations were determined with 3-color immunophenotyping using the lysed whole-blood method. The results were compared with previously published data in healthy children without DS. RESULTS: In healthy children with DS, the primary expansion of T and B lymphocytes seen in healthy children without DS in the first years of life was severely abrogated. The T- lymphocyte subpopulation counts gradually reached more normal levels with time, whereas the B- lymphocyte population remained severely decreased, with 88% of values falling below the 10th percentile and 61% below the 5th percentile of normal. CONCLUSIONS: The diminished expansion of T and B lymphocytes strongly suggests that a disturbance in the adaptive immune system is intrinsically present in DS and is not a reflection of precocious aging. Thymic alterations have been described in DS that could explain the decreased numbers of T lymphocytes, but not the striking B lymphocytopenia, seen in these children.     

Cytogenetic analysis of down syndrome in Libya

The frequency of Down syndrome in Libya was 1 in 516 live births. The mean age of Down mother was 35.62 years. Eighty two percent of the Down mothers were over 30 years of age as compared to 36% of the control Libyan mothers. As there was a greater percentage of late conceptions, the maternal age appears to be influential in the birth of Down syndrome in Libya. Cytogenetically 96% of the cases were that of trisomy 21. There was one case each of mosaic and 21/21 translocation, and four cases of 14/21 translocation as evidenced by Giemsa banding. Twenty two percent of the cases of Down syndrome also had other associated congenital abnormalities. The unique features involved in genetic counselling in this population are discussed. This study reflects the enormous problem of Down syndrome in the Arab world.     

Karyotype evolution in a patient with down syndrome and acute leukemia following a congenital leukemoid reaction

We report the serial cytogenetic study of a patient with Down syndrome who experienced a congenital leukemoid reaction, underwent a spontaneous remission within four months, and subsequently developed acute myeloid leukemia at 16 months. A blood chromosome study to rule out Down syndrome performed at age 24 days, during the leukemoid reaction, revealed a 47,XX,+21 karyotype. The diagnosis of acute leukemia was made at 16 months, at which time a chromosome study, on bone marrow, was performed. This analysis revealed a clonal karyotype of 47,XX,+21,-22,+der (22)t(1;22)(q21;q13) in all but one cell studied. The single apparently nonclonal cell showed a karyotype of 49,XX,+12,-13,-19, +der(19)t(19;?)(q11;?)x2,+21,+22. A third chromosome study at 19 months indicated the original leukemic clone with t(1;22) (q21;q13) had been replaced by the clone represented by the single cell with 49 chromosomes seen in the previous chromosome study. This case of an infant with Down syndrome and acute leukemia illustrated rapid evolution and a transitory nature to clonal chromosome aberrations while retaining AML morphology and course. © 1994 Wiley-Liss, Inc.     

Physical growth of children with down syndrome in India

Anthropometric measurement of 139 Indian children upto the age of five years with Down syndrome, diagnosed by chromosomal studies, were recorded. The height curves of these children fell below the 50th percentile of normal in the first 9 months and subsequently below the 10th percentile. The weight curves remained below the 10th percentile from the beginning and advanced parallel to it with age. Head circumference curves of these children fell appreciably below the 10th percentiles at all ages, but the head continued to grow during the period of study.     

An overview and update regarding medical problems in down syndrome

Down syndrome is the commonest occuring syndrome, and because of the high risk of congenital heart disease, these children are frequently seen at cardiology clinics and wards. However, these individuals are also likely to have a variety of other-problems, both congenital and acquired, which may impinge on the medical and surgical management of cardiac problems. It is therefore important for the paediatric cardiology community to maintain a minimum level of expertise in other noncardiac aspects of the syndrome. This paper reviews Down syndrome, lists congenital and acquire disorders that may occur, and briefly addresses recent advances in the understanding of this condition.     

Medulloblastoma in a child with down syndrome: Long‐term remission with multimodality treatment

A 4¾‐year‐old male with Down syndrome (DS) presented with unsteady gait and fatigue. Neuroimaging revealed a cerebellar mass with concomitant obstructive hydrocephalus and additional metastatic lesions. He was successfully treated and is still in complete remission 5 years from diagnosis. The present case illustrates that, although not yet reported, medulloblastoma can also occur in patients with DS. Pediatr Blood Cancer 2009;53:1150–1151. © 2009 Wiley‐Liss, Inc.     

Transient myeloproliferative disorder and eosinophilic pericardial effusion in a down syndrome neonate

Transient myeloproliferative disorder seen in neonates with Down syndrome is often thought to have a benign course. The authors describe the clinical and laboratory profile of a neonate with Down phenotype and transient myeloproliferative disorder with pericardial effusion as co-morbidity. Pericardial fluid analysis showed eosinophils. Pericardial effusion resolved with prednisolone therapy. Regression in hepatosplenomegaly with clearance of blasts was seen by third week of illness. The clinical course suggested a benign infiltration of the pericardium. Presence of eosinophils supports the differentiating capability of the blast cells in transient myeloproliferative disorders.     

Cholelithiasis in infants with Down syndrome: report of two cases

Down syndrome is a chromosomal disorder most often observed in the newborn period. Various facial, limb and internal abnormalities are found in this disorder but cholelithiasis in infancy has been described in only one report. We report two infants with Down syndrome associated with cholelithiasis. Except for polycythemia and indirect hyperbilirubinemia, no hemolytic process or biochemical abnormalities were evident in both patients. We believe that the cause of gallstones in our cases may have been polycythemia in the newborn period. To our knowledge this is only the second report of gallstones in infancy in Down syndrome.     

Working memory in children and adolescents with Down syndrome: evidence from a colour memory experiment

BACKGROUND: This paper reports information on the visual and verbal short-term memory of individuals with Down syndrome. METHODS: Colour memory in 16 children and adolescents with Down syndrome was compared with that of 16 typically developing children matched for receptive vocabulary. It was suggested that focal colours should be remembered more successfully than non-focal colours on the basis that the former could be remembered using a verbal recoding strategy. However, children with Down syndrome, for whom a deficit in verbal short-term memory makes the use of such a strategy unlikely, should remember focal and non-focal colours equally well. More importantly, if individuals with Down syndrome have more developed visual memory abilities than control children, they should outperform them in recognising non-focal colours. RESULTS: Although the group with Down syndrome demonstrated significantly better Corsi blocks performance than controls, and displayed similar levels of colour knowledge, no advantage for colour memory was found. Non-focal colours were remembered by individuals with Down syndrome as successfully as focal colours but there was no indication of a visual memory advantage over controls. Focal colours were remembered significantly more successfully than non-focal colours by the typically developing children. CONCLUSION: Their focal colour memory was significantly related to digit span, but only Corsi span was related to focal colour memory in the group with Down syndrome.     

Down syndrome and coeliac disease: five new cases with a review of the literature

We report five new patients with coeliac disease and Down syndrome and review the 11 cases previously reported in the literature. In 14 of these 16 patients diarrhoea was the presenting symptom and in 2 failure to thrive in combination with anaemia. The frequency of coeliac disease in children with Down syndrome was calculated as being 43 times greater than in children without Down syndrome. Delay between first symptoms and diagnosis in patients with combined coeliac disease and Down syndrome was 2.5 years, while in the other children with coeliac disease it was only 8 months. This distinctive difference could be caused by an underestimation of the seriousness of gastro-intestinal complaints in patients with Down syndrome. It is stressed that coeliac disease should be strongly considered in all children with Down syndrome and either persistent diarrhoea or failure to thrive.     

Trisomy 21 q: 46,XX,21s+/47,XX,+21q−(q22→qter) mosaicism (de novo) in a down syndrome child

A three year old girl with clinical features of Down syndrome and mental retardation is reported. Karyotype of the proband was 46,XX,21s⁺/47,XX,21q→(q22−qter), resulting in partial trisomy for chromosome 21. Her father, phenotypically normal, was a carrier for 21s+variant chromosome (46,XX,21s⁺). The maternal age was 32 years. This case further confirms that the Down phenotype is due to the trisomy of the distal segment of the band q22 of chromosome 21.     

Spectrum of Di George syndrome in patients with truncus arteriosus: Expanded Di George syndrome

Summary A study of 26 patients with truncus arteriosus showed a high prevalence of facial dysmorphism, aortic arch abnormalities, extracardiac malformations, and significant prenatal risk factors. There was little evidence of parathyroid or thymic abnormalities. However, there was laboratory evidence of immune deficiency, especially T-helper lymphocytes, and clinical evidence of predilection to infection. These findings suggest that patients with truncus arteriosus belong to the spectrum of the Di George syndrome.     

Phonological memory as a predictor of language comprehension in Down syndrome: a five-year follow-up study

BACKGROUND: This study reports the language and memory progress over five years of 30 adolescents and young adults with Down syndrome, and investigates the relationship of earlier phonological memory abilities to later language development. METHODS: Tests of nonverbal ability, receptive vocabulary, grammar comprehension, digit span and nonword repetition were administered at two points in time. RESULTS: For the sample as a whole, there were significant gains in nonverbal ability, receptive vocabulary and grammar comprehension, but no increases in phonological memory measured by nonword repetition or digit span. However, there were considerable individual differences in progress which, in part, were related to chronological age. Phonological memory improved in many younger participants but there were signs of decline in some older ones. Partial correlations between earlier nonword repetition scores and later language scores, controlling for nonverbal ability and earlier language scores, indicated a significant role for phonological memory in the acquisition of vocabulary knowledge. There was similar evidence of a role for phonological memory in grammar comprehension, but only for younger participants. Earlier receptive vocabulary also predicted later nonword repetition scores, particularly for participants with higher levels of vocabulary knowledge. CONCLUSION: Relationships among the processes involved in language and memory development in Down syndrome may be similar to those established for typical development.     

Large granular lymphocyte leukemia (LGL) in a child with hyper IgM syndrome and autoimmune hemolytic anemia

We describe a female with a history of autosomal recessive hyper-IgM (HIGM) syndrome along with a history of autoimmune hemolytic anemia and intermittent lymphadenopathy. She subsequently developed neutropenia, lymphocyostosis and mild thrombocytopenia. Flow cytometry of the peripheral blood revealed the presence of a marked predominance of cytotoxic T lymphocytes, shown to be clonal, with concomitant natural killer (NK) antigen expression. She responded to weekly methotrexate therapy.     

Immunodeficiency in Down's syndrome: Relationship between presence of human thyroglobulin antibodies and HBsAg carrier status

The relationship between the presence of hepatitis B surface antigen (HBsAg) and antibodies to human thyroglobulin (HTgAb) has been studied in 110 subjects with Down's syndrome (DS) from 4 months to 50 years of age and in 122 controls carefully matched for sex, age and socio-environmental conditions. The overall percentage of HBsAg carriers was 22.7 in DS and 6.6 in controls and that of HTgAb-positive subjects was 41.8 in DS and 19.7 in controls. In DS the frequency of HTgAb-positive subjects was very high, even in the youngest age groups in which the percentage of HBsAg carriers was relatively low; the latter thereafter showed a marked increase with age. A positive association between the presence of HBsAg and HTgAb was found only in the oldest age group of DS subjects. It is thus concluded that in DS the high frequency of HTgAb cannot be attributed to chronic hepatitis B virus infection. On the contrary, the presence of HTgAb might well represent an early marker of immunodeficiency and increased susceptibility to infection with hepatitis B virus.This investigation was partly supported by grant No. 76.01345 of the CNR, Rome, Italy