Etiological diagnosis of bilateral, sensorineural hearing impairment in a pediatric Greek population.

Early diagnosis, evaluation and treatment of childhood deafness are essential for a child's normal growth. Etiological diagnosis of hearing loss makes prevention, family scheduling and more effective therapy feasible goals. Etiological assessment of sensorineural deafness still remains difficult although recently with the progress of genetics it has become more efficient. In this retrospective study, the etiology of bilateral, sensorineural hearing loss with indication for hearing aids has been studied in 153 hearing impaired children. Etiological diagnosis was based on family and patient record, physical, audiological and laboratory examinations. Among the 94 children who completed the diagnostic protocol etiological groups revealed the following distribution: non-hereditary acquired hearing impairment was present in 36 children (38%) and hereditary was present in 44 (47%) children. The etiology remained unknown in 14 (15%) children. Non-syndromic autosomal dominant type accounted for 13 (29% of hereditary hearing loss) children, non-syndromic autosomal recessive type for 21 (48%) children and syndromic deafness for 10 (23%) children. Modern diagnostic methods, such as genetic testing, help diminish the number of cases with hearing impairment of unknown etiology, for the benefit of children who receive early and appropriate medical, audiologic, genetic and educational counseling based on the etiology of their hearing loss.

Prelingual nonsyndromic hearing loss in Greece. Molecular and clinical findings.

Mutations in the gene encoding the gap-junction protein connexin 26 (GJB2) on chromosome 13q11 have been shown as a major contributor to prelingual, sensorineural, nonsyndromic deafness. One specific mutation, 35delG, has accounted for the majority of the mutations detected in the GJB2 gene in Caucasian populations and is one of the most frequent disease mutations identified so far with highest carrier frequency of 3,5% in the Greek population. In a collaboration with the major referral centers for childhood deafness in Greece, patients were examined by an extensive questionnaire to exclude syndromic forms and environmental causes of deafness and by allele-specific PCR for the detection of the 35delG mutation. The 35delG mutation was found in 32.1% of the alleles in 173 unrelated cases of prelingual deafness: 50 homozygotes and 11 heterozygotes. Individuals heterozygous for the 35delG mutation were further analyzed by direct genomic sequencing of the coding region of the GJB2 gene, which revealed R184P and 486insT mutations in single alleles. We conclude that the 35delG GJB2 mutation is responsible for one third of prelingual, sensorineural deafness in Greece, which is higher than the usually quoted 20% for Caucasian populations.

M-mode echocardiographic evaluation of systolic function, LV volume and mass in children on growth hormone therapy.

Since abnormal endogenous growth hormone (GH) secretion in adults is associated with cardiac dysfunction, it is important to ensure that GH therapy in children and adolescents does not cause similar effects. Forty-two growth hormone-deficient children (Group 1) (19 girls, 23 boys) were evaluated. Six girls and seven boys were prepubertal with a mean age of 6.65 yr (range 4.37-9.73 yr). Twenty-nine were pubertal (13 girls, 16 boys), mean age 13.57 yr (range 10.08-16.76 yr). The patients had been on long-term GH therapy for 34.97 +/- 18.78 months with an average weekly dose of 17.61 IU/m2/wk. The mean height SDS was -2.85 +/- 1.22 for boys and -2.5 +/- 0.64 for girls at the onset of therapy, and at the time of examination -1.8 +/- 1.32 for the boys and 1.87 +/- 0.94 for the girls. Thirty-four normal control subjects (Group 2) matched for age, sex and body size were also studied. Left ventricular volume (LV), mass and systolic function [shortening fraction (FS)] were evaluated by two-dimensional guided M-mode echocardiography. Blood pressure was also measured. No differences in blood pressure were observed between patients and controls. There was no correlation of GH dose and duration of therapy with LV measurements. No significant differences were found between Group 1 and Group 2. These observations suggest that long term administration of GH does not produce adverse cardiac effects in GH deficient children. Nevertheless, longer follow-up studies are still needed to confirm the safety of long-term rhGH treatment.

Growth and growth hormone therapy in children with achondroplasia: a two-year experience.

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8-12.2 years of age) and 12 girls (5.7-2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week. Auxological assessments were performed 6 months before, at initiation of, and at 6, 12, and 24 months following initiation of growth hormone (GH) therapy. Before initiating GH therapy, hypothalamic-pituitary and thyroid functions were evaluated. Levels of serum insulin-like growth factor (IGF)-I and IGF binding protein (BP)-3 (IGFBP-3) were assessed, as was GH response to provocative stimuli. GH responses in two stimulation tests were normal for all but three children. During the first semester of GH treatment, a significant increase in height velocity (HV), from 3.2 to 8.3 cm/year, was observed in all children. However, during the second semester, a relative decrease in growth rate was observed. By the end of the first year, HV had increased from 3.2 to 6.9 cm/year (mean, 3.7 cm/year; range, 1.1-8 cm/year) in 13 children and remained unchanged in two children. HV declined progressively during the next 12 months and, by the end of the second year of treatment, had increased in seven of the nine children who had completed 2 years of therapy (mean increase, 3.1 cm/year); two children did not respond to GH therapy, as shown by the lack of increase in HV. Sitting-height (SH) to standing-height ratio % (SH%) remained unchanged throughout GH therapy, and no significant change in skeletal maturation was observed. In conclusion, hGH treatment resulted in an increased growth rate in some children with achondroplasia; however, this increase waned during the second year of treatment. Children with the lowest pretreatment HVs seemed to benefit most from GH therapy. Nonetheless, the usefulness of GH treatment in achondroplasia will be known only when a study of final height is completed.

Melnick-Needles syndrome in a mother and her son.

The Melnick-Needles syndrome is a rare connective tissue disorder characterised by specific facial features (small facial bones, exophthalmos, hypertelorism, full checks and small mandible), skeletal defects and short stature. The syndrome is considered to be lethal in males. Nevertheless, five surviving males are considered to represent new mutations. We are presenting an affected surviving male with the Melnick-Needles syndrome born to an affected mother.

Familial bilateral blepharoptosis and subvalvular aortic stenosis.

A boy and his mother with bilateral congenital blepharoptosis, downslanting palpebral fissures, hypertelorism, microcephaly, short nose with flattened nasal root, microstomia, prominent lateral palatine ridges, bifid (boy) hypoplastic (mother) uvula, generalized dental caries, short neck, peculiar voice and mild conductive deafness are reported. The boy had subvalvular aortic stenosis. The mother had pectus excavatum but not any signs or symptoms of cardiovascular defect.