Can a fixed measure serve as a pertinent diagnostic criterion for large vestibular aqueduct in children?

Background A vestibular aqueduct midpoint width greater than 1.50 mm is currently considered to be pathognomonic for a large vestibular aqueduct syndrome. Objective To analyse the diameter of the vestibular aqueduct in children as a function of age and consequently to determine if a fixed measure could serve as a pertinent diagnostic criterion. Materials and methods This was a retrospective study of 200 high-resolution CT scans of the ear in 100 patients aged 0–16 years and from various paediatric medical departments. On each CT scan, the lateral semicircular canal diameter, the vestibular aqueduct midpoint width between the external aperture and common crus, and the vestibular aqueduct external aperture diameter were measured. Spearman’s rank test and the Mann-Whitney correlation test were used for an integrated statistical analysis. Results There was no statistically significant variability in vestibular aqueduct diameter as a function of age or sex of patients. Conclusion A CT scan threshold value, fixed and independent of age and sex, is thus legitimate for the diagnosis of vestibular aqueduct dilatation.     

Phenotypic spectrum of CHARGE syndrome with CHD7 mutations

CHD7 gene mutations were identified in 17 (71%) of 24 children clinically diagnosed to have CHARGE syndrome (C, coloboma of the iris or retina; H, heart defects; A, atresia of the choanae; R, retardation of growth and/or development; G, genital anomalies; and E, ear abnormalities). Colobomata, hearing loss, laryngomalacia, and vestibulo-cochlear defect were prevalent. Molecular testing for CHD7 enables an accurate diagnosis and provides health anticipatory guidance and genetic counseling to families with CHARGE syndrome.     

T-cell immunodeficiency in CHARGE syndrome

CHARGE syndrome comprises coloboma of the eye, heart defects, choanal atresia, growth and developmental retardation, genitourinary anomalies and ear and hearing defects. The association between CHARGE syndrome and T-cell immunodeficiency is recognized, but has not been reported widely in the literature. We report four patients meeting the diagnostic criteria for CHARGE syndrome, who had moderate or severe T-cell lymphopenia complicated by infections. The patients presented in Leicester, UK, between 2000 and 2007. All patients were negative for 22q11.2 deletions by FISH analysis, but mutations in the CHD7 gene were identified in three patients in whom the analysis was performed. Our cases indicate that patients with CHARGE syndrome may have a spectrum of T-cell immune deficiency, and that this association may be more common than has previously been appreciated. We recommend that all patients diagnosed with CHARGE syndrome should have lymphocyte subsets evaluated as part of their initial investigation.
Conclusion: Thymic hypoplasia should be included in the clinical features associated with CHARGE syndrome. All patients with CHARGE syndrome should have lymphocyte subset analysis performed, to exclude T-cell immunodeficiency.     

Inner ear anomalies seen on CT images in people with Down syndrome

Background

Although dysplasia of inner ear structures in Down syndrome has been reported in several histopathological studies, the imaging findings have not been widely studied.

Objective

To evaluate the prevalence and clinical significance of inner ear anomalies detected on CT images in patients with Down syndrome.

Materials and methods

The temporal bone CT images of patients with Down syndrome were assessed for inner ear anomalies; clinical notes and audiograms were reviewed for hearing loss. Logistic regression models were employed to identify which CT findings were associated with sensorineural hearing loss (SNHL).

Results

Inner ear anomalies were observed in 74.5% (38/51) of patients. Malformed bone islands of lateral semicircular canal (LSCC), narrow internal auditory canals (IACs), cochlear nerve canal stenoses, semicircular canal dehiscence (SCCD), and enlarged vestibular aqueducts were detected in 52.5% (53/101), 24.5% (25/102), 21.4% (21/98), 8.8% (9/102) and 2% (2/101) of patients’ ears, respectively. IAC stenosis had the highest odds ratio (OR?=?5.37, 95% CI: 1.0–28.9, P?=?0.05) for SNHL.

Conclusion

Inner ear anomalies occurred in 74.5% of our population, with malformed (<3?mm) bone island of LSCC being the most common (52.5%) anomaly. Narrow IAC was seen in 24.5% of patients with Down syndrome and in 57.1% of ears with SNHL. High-resolution CT is a valuable for assessing the cause of hearing loss in people with Down syndrome.     

Choanal atresia: management and surgical treatment. Study of 50 cases]

Diagnosis of choanal atresia should lead to multidisciplinary investigations to look for other malformations which may or may not be part of the CHARGE syndrome. These concomitant defects have an adverse effect on prognosis in patients with choanal atresia. They seem to be more common in patients with bilateral choanal atresia due to a bony septum. Local investigations include nasal fiberoptic endoscopy to obtain a direct view of the atresia and a CT scan study to determine the type of obstruction. In neonates, treatment rests on transnasal perforation of the septum followed by stenting for four to six weeks. However recurrence is common and requires subsequent use of another therapeutic procedure. In patients with failed transnasal perforation or unilateral choanal atresia discovered at a later age, surgery through the palatal route seems to be virtually radical and can be carried out from eight months of age. Recently developed CO2 laser therapy is, in the opinion in of the authors, an elegant and simple means for transnasal treatment of fibrotic restenosis which, in many cases, obviates the need for transpalatal surgery.     

Vestibular neuronitis in a teenager with sickle cell disease. Treatment is urgent

Vestibular syndrome is not frequently described in patients with sickle cell disease. We report the case of a teenager with sickle cell disease who had a vestibular syndrome with vertigo that successfully responded to exchange transfusion. We discuss guidelines and review the literature in view of this case report. Sensorineural disorders should be considered as stroke syndromes. They require urgent treatment consisting of exchange transfusion or maintaining optimal hydration associated with blood withdrawal. Treatment of vestibular syndrome in sickle cell disease is urgent.     

Contribution of fetal MRI to the diagnosis of inner ear abnormalities: report of two cases

We report two cases of fetal inner ear abnormalities diagnosed by MRI. Cerebral MRI was performed on two fetuses, at 32 and 30 weeks gestation, following US that demonstrated multiple malformations suggestive of CHARGE syndrome in one fetus and ventriculomegaly and poor visibility of the posterior fossa in the other. MRI revealed vestibular hypoplasia and agenesis of the semicircular canals in one fetus and cystic cochleas, partial vermian agenesis and an occipital meningocele in the second fetus. Both pregnancies were terminated and there was good correlation between fetal MRI, ex utero CT and fetopathological findings. The inner ears should be carefully examined when performing fetal cerebral MRI because abnormalities of the inner ear may be associated with cerebral anomalies.     

Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association

We report 21 patients with choanal atresia or ocular coloboma or both who have certain other associated anomalies, including congenital heart disease, postnatal growth deficiency, mental retardation and/or CNS anomalies, microphallus and cryptorchidism, and ear anomalies and/or deafness. Facial palsy, micrognathia, cleft palate, and swallowing difficulties were also common. It has not been possible to define a single etiology or a syndrome in these patients. We propose the mnemonic CHARGE (C-coloboma, H-heart disease, A-atresia choanae, R-retarded growth and retarded development and/or CNS anomalies, G-genital hypoplasia, and E-ear anomalies and/or deafness) to describe the features of this association.     

Congenital funnel anus in children: associated anomalies,surgical management and outcome

Funnel anus (FA) is a rare and distinct type of anorectal malformation characterized by a skin-lined deep anal funnel, missing transitional epithelium and stenosis secondary to fibrotic internal sphincter. We aimed to characterize associated anomalies, surgical management and outcome of children with FA. The hospital records of 11 consecutive children (7 boys) treated for FA between 1992 and 2006 were screened. The collected data included the type of anorectal malformation, surgical management, associated anomalies, results of diagnostic investigations and outcome. Only one patient was free of any associated malformation. Six patients had a complete Currarino syndrome. Seven patients had a hemisacrum (scimitar) and tethered cord was present in two cases. Six patients underwent excision of a benign presacral teratoma. Anal stenosis associated with FA was managed by serial dilatations. Subsequent resection of the megarectosigmoid secondary to refractory constipation was performed on five occasions. Three patients underwent coloanal pull-through for Hirschsprung’s disease (HD). The level of aganglionosis was at the rectosigmoid junction in two cases and low in the rectum in one. One additional patient had hypoganglionosis. Of the three patients with HD two also had Down’s syndrome. After median follow-up of 6.5 (0.3–13.5) years four patients have normal bowel function and four suffer from soiling. Two patients with HD and Down’s syndrome and one patient with an undefined syndrome are fecally incontinent. Associated anomalies are common and diverse in children with FA. Pelvic MRI, sacral radiography, evaluation of the urinary tract and rectal biopsies are recommended as routine investigations in cases of FA. Surgical care of these patients is demanding and should be confined to dedicated centers.     

Vertigo in children]

The main difference between childhood and adulthood vertigo is that the evaluation of symptoms and examination pose special challenges in pediatric patients, depending on age. Vertigo in pre-teenage children is similar to vertigo in adults. In contrast, although benign paroxysmal vertigo, vestibular neuronitis, and Ménière's vertigo occur in children, the distribution of these conditions is different from that seen in adults. After vestibular and cochlear investigations as well as a CT scan or MRI study to outrule a tumor of the posterior cerebral fossa, the diagnosis of vestibular vertigo is established. Often, the diagnosis proposed cannot be considered as final and requires reappraisal according to the long-term course. Collation of case-reports with highly accurate documents is essential in order to strive to develop more satisfactory approaches.     

Hydrocephalus and mental retardation in craniosynostosis

We prospectively studied craniosynostosis, regardless of neurologic status, by cranial computed tomography or psychometric testing in 56 children. None of the 27 children with simple craniosynostosis (single or multiple suture involvement) had evidence of hydrocephalus on CT scan. Of the 24 patients with simple craniosynostosis who underwent psychometric testing, 17 were of average intelligence; six were in the low average range. The single mentally retarded child had a history of severe perinatal asphyxia. Hydrocephalus occurred more frequently (five of 23 cases) in children with complex craniosynostosis syndromes, including Pfeiffer syndrome, Crouzon syndrome, and kleeblattsch?del deformity. More striking than hydrocephalus, however, was the finding of dysmorphic ventricular dilation in eight patients, including the three children with Apert syndrome and four with Crouzon syndrome. Nineteen of the 25 children with complex craniosynostosis syndromes receiving psychometric testing were of normal intelligence. Four children with borderline normal intelligence had either hydrocephalus or ventricular dilation. The two children with mental retardation were sisters with Crouzon syndrome whose family included other retarded individuals. This study indicates that the incidence of hydrocephalus and mental retardation in craniosynostosis is lower than reported previously.     

Evaluation of vestibular functions in children with vertigo attacks

Aim: To examine vestibular system functions in children with episodic vertigo attacks. Methods: Thirty four children (20 males) aged 4–18 years with paroxysmal dizziness and/or vertigo attacks were evaluated. A medical history for vestibular symptoms and migraine was taken. Vestibular and auditory functions were assessed. Results: Chronic headache attacks consistent with migraine were reported in 12 children and motion sickness was reported in 30. Family history in first degree relatives was positive for migraine in 29 children and for episodic vertigo in 22. Electronystagmography and videonystagmography showed two types of nystagmus: spontaneous vestibular nystagmus (41%) and benign paroxysmal positional nystagmus (BPPN) (59%). The first type of nystagmus was assessed as a sign of vestibulopathy and the patients with BPPN were diagnosed as having benign paroxysmal positional vertigo (BPPV). Audiometric examination in four cases revealed bilateral sensory neural hearing loss in low frequencies. Pure tone averages in 30 cases were within normal ranges; however low frequencies in 28 of them were approximately 10 dB lower than high frequencies. Unilateral caloric responses diminished in eight children. Conclusions: Peripheral vestibular problems in childhood present in a wide spectrum, which varies from a short episode of dizziness to a typical vestibular attack with fluctuating sensory neural hearing loss or episodes of BPPV. A considerable number of these vestibular problems might be related to the migraine syndrome.     

小儿反复肺炎的基础疾病和诊断分析

目的　探讨小儿反复肺炎的基础疾病和诊断方法。方法　回顾性分析了 1997年 12月至 2 0 0 2年 12月北京儿童医院 10 6例反复肺炎患儿的临床资料。结果　 10 6例反复肺炎患儿中 94例 (88 7% )存在基础疾病 ,其中先天性或获得性呼吸系统解剖异常 4 1例 (43 6 % ) ,呼吸道吸入 15例 (15 9% ) ,先天性心脏病 12例 (12 8% ) ,哮喘 9例 (9 6 % ) ,免疫缺陷病 8例 (8 5 % ) ,原发纤毛不动综合征 5例 (5 3% ) ,特发性肺含铁血黄素沉着症 3例(3 2 % ) ,肺肾综合征 1例 (1 1% )。反复肺炎患儿各种基础疾病各有其病史、体格检查和X线胸片表现特点 ,在此基础上多数基础疾病通过多项检查确诊。结论　儿童反复肺炎多存在基础疾病 ,最常见的是先天性或获得性呼吸系统解剖异常 ,其次为呼吸道吸入、先天性心脏病、哮喘、免疫缺陷病和原发性纤毛不动综合征等。病史、体格检查和X线胸片可以为进一步的检查提供重要线索 ,特殊检查如胸部CT和纤维支气管镜等是多数儿童反复肺炎基础疾病诊断的主要依据。     

Role of rare cases in deciphering the mechanisms of congenital anomalies: CHARGE syndrome research

In this review, our work on CHARGE syndrome will be used to exemplify the role of rare cases in birth defects research. The analysis of 29 cases with mutations of CHD7, the causative gene for CHARGE syndrome, clarified the relative importance of the cardinal features, including facial nerve palsy and facial asymmetry. Concurrently, in situ hybridization using chick embryos studies were performed to delineate the expression pattern of Chd7. The Chd7-positive regions in the chick embryos and the anatomical defects commonly seen in patients with CHARGE syndrome were well correlated: expression in the optic placode corresponded with defects such as coloboma, neural tube with mental retardation, and otic placode with ear abnormalities. The correlation between expression in the branchial arches and nasal placode with the clinical symptoms of CHARGE syndrome, however, became apparent when we encountered two unique CHARGE syndrome patients: one with a DiGeorge syndrome phenotype and the other with a Kallman syndrome phenotype. A unifying hypothesis that could explain both the DiGeorge syndrome phenotype and the Kallman syndrome phenotype in patients with CHARGE syndrome may be that the mutation in CHD7 is likely to exert its effect in the common branch of the two pathways of neural crest cells. As exemplified in CHARGE syndrome research, rare cases play a critical role in deciphering the mechanisms of human development. Close collaboration among animal researchers, epidemiologists and clinicians hopefully will enhance and maximize the scientific value of rare cases.     

Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism

It is rare that coloboma, heart anomalies, choanal atresia, retarded growth and development, and genital and ear anomalies (CHARGE) syndrome patients have DiGeorge sequence showing severe immunodeficiency due to the defect of the thymus. Although the only treatment to achieve immunological recovery for these patients in countries where thymic transplantation is not ethically approved would be hematopoietic cell transplantation, long-term survival has not been obtained in most patients. On the other hand, it is still not clarified whether hypoparathyroidism is one of the manifestations of CHARGE syndrome. We observed a CHARGE syndrome patient with chromodomain helicase DNA-binding protein 7 mutation showing DiGeorge sequence including the defect of T cells accompanied with the aplasia of the thymus, severe hypoparathyroidism, and conotruncal cardiac anomaly. He received unrelated cord blood transplantation without conditioning at 4 months of age. Recovery of T cell number and of proliferative response against mitogens was achieved by peripheral expansion of mature T cells in cord blood without thymic output. Although he is still suffering from severe hypoparathyroidism, he is alive without serious infections for 10 months.     

Neurofibromatosis type 2 diagnosed in the absence of vestibular schwannomas. A case report and guidelines for a screening protocol for children at risk

 A 5-year-old girl presented with multiple tumours of the central nervous system. As on the first MRI scan bilateral vestibular schwannomas were not detected due to their small size, she initially did not meet the criteria for neurofibromatosis type 2 (NF2), although her clinical symptoms were highly suggestive for the diagnosis. Using molecular studies, a mutation in the NF2 gene was found confirming the clinical suspicion at an early age and indicating the value of molecular analysis. Follow-up MRI 3 years later demonstrated bilateral vestibular schwannomas more clearly, since they had increased in size. Conclusion In children, magnetic resonance imaging can be inconclusive for the diagnosis of neurofibromatosis type 2, since very small vestibular schwannomas may be missed. In these cases molecular studies may provide additional evidence for the diagnosis. We propose guidelines for a screening protocol for children at risk for having neurofibromatosis type 2. Received: 11 October 2000 / Accepted: 27 February 2001     

CHARGE – von einer Assoziation zum Syndrom

CHARGE syndrome is an autosomal dominant syndrome with a high clinical variability. The disorder consists of coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear anomalies and deafness, often in combination with hypoplasia of the semicircular canal. CHARGE syndrome is common, with an estimated incidence of 1/10,000–15,000 newborns. The underlying cause are mutations in the CHD7 gene. The CHD7 protein belongs to a group of conserved proteins that are thought to play an important role in chromatin organization and regulation of gene expression. The known mutations are spread all over the whole gene; therefore, mutational analyses of all coding sequences and exon/intron boundaries of the gene are necessary for molecular diagnostics, which would be helpful in situations of diagnostic uncertainty.     

Cohen syndrome: two new cases in siblings

Cohen syndrome is a rare genetic disorder consisting of truncal obesity, hypotonia, mental retardation, characteristic facial appearance and ocular anomalies. Other diagnostic clinical features include narrow hands and feet, low growth parameters, neutropenia and chorioretinal dystrophy. We describe the similarities in the clinical and developmental profile of two siblings with Cohen syndrome, providing evidence for autosomal recessive inheritance in this condition. Conclusion The diagnosis of Cohen syndrome should be suspected in mentally retarded children with the above characteristics. Neutropenia and ocular anomalies with high-grade myopia and chorioretinal dystrophy are also considered important findings and can aid in the clinical diagnosis especially at an early age. Received: 22 December 1998 / Accepted: 29 March 1999     

Evaluation of vestibular functions in children with vertigo attacks.

AIM: To examine vestibular system functions in children with episodic vertigo attacks. METHODS: Thirty four children (20 males) aged 4-18 years with paroxysmal dizziness and/or vertigo attacks were evaluated. A medical history for vestibular symptoms and migraine was taken. Vestibular and auditory functions were assessed. RESULTS: Chronic headache attacks consistent with migraine were reported in 12 children and motion sickness was reported in 30. Family history in first degree relatives was positive for migraine in 29 children and for episodic vertigo in 22. Electronystagmography and videonystagmography showed two types of nystagmus: spontaneous vestibular nystagmus (41%) and benign paroxysmal positional nystagmus (BPPN) (59%). The first type of nystagmus was assessed as a sign of vestibulopathy and the patients with BPPN were diagnosed as having benign paroxysmal positional vertigo (BPPV). Audiometric examination in four cases revealed bilateral sensory neural hearing loss in low frequencies. Pure tone averages in 30 cases were within normal ranges; however low frequencies in 28 of them were approximately 10 dB lower than high frequencies. Unilateral caloric responses diminished in eight children. CONCLUSIONS: Peripheral vestibular problems in childhood present in a wide spectrum, which varies from a short episode of dizziness to a typical vestibular attack with fluctuating sensory neural hearing loss or episodes of BPPV. A considerable number of these vestibular problems might be related to the migraine syndrome.