Down syndrome: otolaryngological effects of rapid maxillary expansion.

OBJECTIVE: Phenotypical Down syndrome includes pharyngeal and maxillary hypoplasia and, frequently, constricted maxillary arch with nasal obstruction. STUDY DESIGN: This clinical trial assessed the effects of rapid maxillary expansion on ENT disorders in 24 children with Down syndrome randomly allocated to receive either rapid maxillary expansion or not. Each group received ENT and speech therapy assessments before expansion and after the device had been removed. RESULTS: In the rapid maxillary expansion group, the yearly ENT infection rate was reduced when assessed after device removal (p < 0.01). The parents of rapid maxillary expansion children reported a reduction in respiratory obstruction symptoms. Audiological assessment revealed improvements in the rapid maxillary expansion group (p < 0.01). Cephalometry showed increased maxillary width in the rapid maxillary expansion group. CONCLUSIONS: Rapid maxillary expansion resulted in a reduction in hearing loss, yearly rate of ENT infections and parentally assessed symptoms of upper airway obstruction, compared with no treatment. These findings are probably related to expanded oronasal space, due to rapid maxillary expansion.

Novel mutations in the GALK1 gene in patients with galactokinase deficiency.

Galactokinase deficiency is an inborn error of galactose metabolism whose major clinical manifestation is the development of cataracts during the first months of life. Only 20 mutations have been reported to date and understanding of the functionally important domains of the galactokinase protein is still limited. Here we report four novel mutations in GALK1 that were identified in two unrelated patients with galactokinase deficiency. Three of these were amino acid substitutions: 1569C-->T in exon 2 (R68C); 7093C-->T in exon 6 (T288M) and 7538G-->C in exon 8 (A384P). In addition, a single base-pair deletion was found in exon 5 (2833delC), predicted to result in a shift of the reading frame and a premature termination codon at position 263. Some differences with the GALK1 sequence deposited in Genbank are also reported.

A prevalence study of celiac disease in persons with Down syndrome residing in the United States of America.

In order to estimate the prevalence of celiac disease in persons with Down syndrome, 105 patients with this chromosomal disorder residing on the East Coast of the United States of America were enrolled in this study. IgA and IgG antigliadin antibodies (AGA) were determined using a fluorescent immunoenzymatic assay, and antiendomysium antibodies (AEA) were measured with immunofluorescence on monkey oesophagus. Of the 105 patients, 5 were positive for AEA, 4 were positive for IgG AGA, and 1 was positive for IgG AGA and AEA. Of the five patients with high titres of AEA, four consented to a jejunal biopsy, which revealed significant villous atrophy. Thus, 4 (possibly 5) patients in this cohort of 105 individuals with Down syndrome have celiac disease.

Should children with Down syndrome be screened for atlantoaxial instability?

In 1995, the Committee on Sports Medicine and Fitness of the American Academy of Pediatrics (AAP) published a position paper on atlantoaxial instability in children with Down syndrome in which a previous statement on the same subject published in 1984 (Table) was retired. The 1995 statement includes several arguments that disfavor screening of children with Down syndrome for atlantoaxial instability. Whereas some of these arguments are well founded, other lack substantive evidence that would support the statement. In the following discussion, I attempt to analyze some of these arguments made in the 1995 statement and provide a viewpoint that favors radiologic examinations of the cervical spine of children with Down syndrome.

Towards optimal mental health of persons with Down syndrome.

This paper outlines the risk of mental health disorders in adults with Down syndrome and considers the practical ways in which positive well-being can be promoted. It emphasises that prevention begins at birth and parents need to be alerted to positive child-rearing strategies from infancy.

Cerebrohepatorenal (Zellweger) syndrome: clinical, neuropathological, and biochemical findings.

An infant with Zellweger syndrome is reported. A detailed description of the clinical findings is provided. In particular, the neuropathological aspects are highlighted and the underlying biochemical derangements discussed. In addition, some of the known pathogenetic mechanisms that are involved in producing the phenotype of Zellweger syndrome are analyzed.

Major depression in a small group of adults with Down syndrome.

The clinical histories and treatment of the nine individuals with Down syndrome (DS) and major depression (MD) previously noted in a report on the psychopathology of a population of 164 adults with DS with and without health disorders from a Down Syndrome Clinic are presented (Myers & Pueschel, 1991). The clinical characteristics including DSM-III-R (1987) criteria of these 9 patients plus 13 individuals with DS and MD described in case reports in the literature are summarized. Depression is rarely verbalized and commonly appears as crying, depressed appearance, or mood lability. Vegetative symptoms of disinterest with severe withdrawal and mutism, psychomotor retardation, decreased appetite, weight loss, and insomnia are prominent. Verbal expression of preoccupations of suicide, death, self-depreciation, and guilt were infrequent and may either be not present or not reported due to mutism or moderate level of mental retardation (MR). Hallucinations were prominent. Family history of depression was infrequent. Psychological stressors were noted mostly in the study sample and not in the 13 from the literature. The pattern of vegetative symptomatology with few verbal complaints and prominent hallucinations may be related to moderate mental retardation in these groups with DS rather than specifically to DS.

Guidelines for optimal medical care of persons with Down syndrome. International League of Societies for Persons with Mental Handicap (ILSMH).

There are numerous clinical conditions observed in persons with Down syndrome, as described above, which should be taken into consideration in the course of their medical care and management. If provided with optimal medical services, pursuing specific evaluations and examinations, with a focus on preventive aspects and fostering well being in all areas of human functioning, the quality of life of individuals with Down syndrome can be enhanced significantly and their contribution to society substantial.

Tardive or atypical Tourette's disorder in a population with Down syndrome?

In a population of 425 individuals with Down syndrome, we observed 5 persons (1.2%) with Tourette's disorder. Because the prevalence of Tourette's disorder in the general population has been estimated to be between 0.03% and 1.6%, it is not likely that there is an increased prevalence of Tourette's disorder in Down syndrome, or that there is an interrelationship between Down syndrome and Tourette's disorder. This lack of relationship argues against an atypical Tourette's disorder. The absence of family histories of Tourette's disorder in our patients, the relatively late onset of the disorder in most of our patients, their previous treatment with neuroleptic and psychostimulant medication, and the lack of relationship between Down syndrome and Tourette's disorder in this Down syndrome population are factors that support the diagnosis of tardive Tourette's disorder.

Posterior occipitoatlantal hypermobility in Down syndrome: an analysis of 199 patients.

We endeavored to determine the prevalence of occipitoatlantal hypermobility in individuals with Down syndrome, to establish objective radiographic criteria for this entity, and to correlate this with neurologic abnormality. In a retrospective analysis, upper cervical spine radiographs of 210 patients with Down syndrome were compared with those of 102 normal individuals. Radiographs were evaluated using the Powers ratio. Patients identified with radiographic evidence of posterior occipitoatlantal hypermobility were then examined clinically and compared with a matched group of patients with Down syndrome and normal Powers ratios. Of the patients with Down syndrome, 8.5% had a Powers ratio of < 0.55, which was indicative of posterior occipitoatlantal hypermobility (POAH). Furthermore, 66% of those with an abnormal Powers ratio had positive neurologic findings upon physical exam, a finding that was statistically significant when compared to a matched group of patients with Down syndrome and normal Powers ratio.

Environmental and temperament assessments of children with Down's syndrome.

This study was designed to investigate the family environment and the temperament of children with Down's syndrome (DS). Parents of 40 children with DS completed the Family Environmental Scale (FES). They also were asked to fill out the Temperament Assessment Battery for Children (TABC) for both the child with DS and the nearest same-sex sibling. A similar questionnaire of the TABC (teacher form) was sent to the children's teachers. The results of these investigations revealed that there were high scores in categories cohesion, expressiveness, achievement, moral/religious emphasis, organization and control on the FES, indicating that family members in the study cohort are relationship oriented, provide support for one another, emphasize ethical values and are able to express their feelings. Comparing TABC results between children with DS with their siblings, significant differences were observed in such categories as adaptability, approach/withdrawal and persistence. Control children were scoring higher in the adaptability and persistence categories, whereas children with DS achieved significantly higher scores than the control children in the approach/withdrawal category.

Mitral valve prolapse in persons with Down syndrome.

This study was designed to determine the prevalence of mitral valve prolapse and aortic insufficiency in home-reared, young persons with Down syndrome. Of the 36 individuals (ages 20-32 years) enrolled in this study, 20 had abnormal echocardiographic findings. Thirteen patients had mitral valve prolapse, 3 had both mitral valve prolapse and aortic insufficiency, 2 had only aortic insufficiency, and 2 had other mitral valve disorders. In 14 of the 16 patients with mitral valve prolapse, a midsystolic click was heard. Theories of the pathogenesis and possible complications of mitral valve prolapse and its relationship to exercise and sport activities are discussed.

Elevated erythropoietin levels in cord blood of newborns with Down's syndrome.

Plasma erythropoietin (Ep) was determined in umbilical cord blood in 18 infants with Down's syndrome. The 16 infants with Down's syndrome who were delivered after labor had significantly elevated plasma Ep levels compared to 36 control infants born after labor (p < 0.001). Six of the ten infants with Down's syndrome who had their packed cell volume (PCV) measured in the first 24 h of life were polycythemic based on a PCV of > or = 0.65. The presence of congenital heart disease in 9 of the 18 infants with Down's syndrome was not associated with a higher plasma Ep or PCV levels. Plasma Ep was correlated with neonatal PCV in the combined group of control and Down's syndrome infants (p = 0.003). Increased plasma Ep levels observed in infants with Down's syndrome suggested chronic fetal hypoxemia as a likely explanation for the high incidence of neonatal polycythemia observed in this group.

Sleep-disordered breathing and behavior in three risk groups: preliminary findings from parental reports.

Sleep-related breathing disorders may cause excessive daytime sleepiness, cognitive impairment, and behavior problems in children and adolescents. Adenotonsillar enlargement (AT) is known to be a significant risk factor for these disorders, which have also been reported in several patients with Down syndrome (DS). Children with attention deficit disorder/hyperactivity (ADD) show behavior problems that may be related to disturbed nocturnal sleep in some. To evaluate the relationships among these disorders and symptoms, parents of 29 school-aged children with AT, 70 with DS and 48 of their siblings (DS-SIB), and 21 with ADD completed a 20-item screening questionnaire covering nocturnal sleep symptoms and daytime behavior problems. Nocturnal symptoms of sleep-related breathing disorders--snoring, breathing pauses during sleep--were reported more commonly by parents of AT and DS children. However, parents of two of the ADD children reported significant signs of sleep-related breathing disorders. Daytime behavior problems were more common in ADD and AT than in the DS group. Bedwetting reports did not distinguish groups. Direct comparisons of DS and DS-SIB groups showed that more DS were mouth breathers, snored, stopped breathing at night, and were sleepy in the daytime. These findings underscore the importance of obtaining a history of nocturnal sleep from parents of children with AT and DS, as well as those with disrupted daytime behavior.

Growth hormone response after administration of L-dopa, clonidine, and growth hormone releasing hormone in children with Down syndrome.

We studied the response of growth hormone secretion after the administration of L-dopa, clonidine, and growth hormone releasing hormone in eight growth-retarded children with Down syndrome aged 1 to 6.5 years. After L-dopa administration, five children had low growth hormone secretion (M = 3.7 ng/ml, SD = 2.12 at 30 min) and three children had elevated growth hormone levels (> 30 ng/ml). After clonidine administration, six children had relatively low growth hormone levels (M = 3.15 ng/ml, SD = 2.53 at 60 min) and two children had high levels (38.3 ng/ml and 16.8 ng/ml, respectively). There was a better response after growth hormone releasing hormone administration; only one child had a growth hormone level of < 10 ng/ml. Most of the children had a modified response of growth hormone secretion subsequent to the various stimulation tests. All children, however, were able to secrete some growth hormone (> or = 10 ng/ml) at least during one of the stimulation tests. In comparison with peak growth hormone levels reported in normal children, our cohort had significantly lower growth hormone levels only after clonidine administration. It is postulated that children with Down syndrome have both anatomical and biochemical hypothalamic derangements that may result in decreased growth hormone secretion and reduced linear growth. In addition, other mechanisms that may be in part responsible for the observed growth retardation are discussed.

Molecular characterization of cytogenetic alterations associated with the Beckwith-Wiedemann syndrome (BWS) phenotype refines the localization and suggests the gene for BWS is imprinted.

To define the region of 11p15 involved in Beckwith-Wiedemann syndrome (BWS), we have carried out a molecular genetic analysis of six patients with features of BWS and constitutional cytogenetic abnormalities involving chromosome band 11p15. Molecular analysis confirmed the 11p origin of the duplicated material and defined the smallest region of overlap for such duplications, within which a gene involved in BWS must be located. This region encompasses the beta-globin gene complex (HBB) to 11pter. In both of our informative cases, the 11p duplication was found to be of paternal origin. Two BWS associated balanced translocations of 11p15 were studied to localize the breakpoints on 11p15. Somatic cell hybrids, Southern blotting and fluorescent in situ hybridization (FISH) showed that both breakpoints were between D11S12 and the insulin-like growth factor 2 (IGF2) gene. A non-BWS translocation breakpoint was more proximal, between HBB and calcitonin-A (CALCA). Pedigree analysis showed that both BWS associated 11p15 translocations were transmitted by phenotypically normal mothers. The data are compatible with the hypothesis that the BWS gene is imprinted and that the maternally inherited BWS gene is normally suppressed whereas the paternally inherited allele is active. Thus, duplications of paternal origin would lead to increased dosage of the BWS gene. Similarly increased dosage of the BWS gene could account for the findings in maternally inherited 11p15 translocations by altering normal imprinting, so that the translocated maternal allele remains active. This study defines one or more gene loci for BWS on 11p15.5 in the genomic region from D11S12 to IGF2.

Reflex seizures in Down syndrome.

A unique patient with Down syndrome who developed reflex seizures is described. The patient has had recurrent intermittent seizures for the past 3.5 years. These seizures were usually precipitated by auditory stimuli such as sudden loud noises. While having seizures the patient experienced severe discomfort in the posterior neck area. The seizures usually lasted 10-20 s, and there was no aura, nor was there a postictal phase. Of the numerous investigations performed, closed-circuit electroencephalogram video telemetry was most helpful in arriving at an accurate diagnosis. Carbamazepine administration resulted in total seizure control and reflex stimuli no longer provoke seizure activity. Although it has been suggested that reflex seizures may be due to genetic factors or structural central nervous system defects, we were unable to uncover the cause of the reflex seizures in our patient.

Lipids and lipoproteins in persons with Down's syndrome.

This study was designed to investigate whether the observed decreased prevalence of coronary artery disease in individuals with Down's syndrome may be explained by their serum lipid and lipoprotein profiles. Twenty-seven persons with Down's syndrome and 23 non-affected control individuals were enrolled in this study. Their fasting venous blood was analysed for total cholesterol, triglyceride, LDH cholesterol, HDL cholesterol, apo B and apo AI. The results revealed no significant differences between the study and control group with regard to total cholesterol, LDL cholesterol, apo B and the apo B:apo AI ratio. However, triglyceride levels were significantly increased, and serum HDL cholesterol, apo AI and HDL cholesterol:total cholesterol ratio were significantly decreased in patients with Down's syndrome when compared with the control group. The latter observations are all associated with an increased risk for coronary artery disease. Therefore, it is concluded that the decreased prevalence of coronary artery disease in individuals with Down's syndrome cannot be explained by the lipid and lipoprotein levels observed in this study population.