New Feeding Assessment Scale for individuals with genetic syndromes: Validity and reliability in the CHARGE syndrome population.

AIM: To develop a feeding scale for parents/care givers of individuals of all ages with genetic syndromes experiencing extensive feeding and swallowing problems. Second, to assess its validity and reliability in CHARGE syndrome. METHODS: The new Feeding Assessment Scale (FAS) was adapted from a scale for children who need prolonged tube feeding (Paediatric Assessment Scale for Severe Feeding Problems, PASSFP). Ten parents piloted the new scale before it was sent out with the PASSFP and feeding history questions. A subset completed the new scale again 4-8 weeks later. RESULTS: One hundred parents of individuals with CHARGE syndrome participated from around the world. The new scale had good construct validity, with a significant effect for an increased number of feeding risk factors having higher scale scores (P < 0.001). Face validity was high, as scores significantly differed between individuals whose parents identified their feeding difficulties as very mild, mild, moderate, severe and very severe (P < 0.001). Test-retest reliability (r = 0.94, P < 0.001) and internal consistency (Cronbach's alpha 0.91) were both high. There was significant convergent validity between the new scale and the PASSFP (r = -0.79, P < 0.001). CONCLUSIONS: This new tool is reliable and valid for parents/care givers of individuals with CHARGE syndrome. It can be used to assess the current severity of feeding difficulties and to track progress before and after treatment. It expands upon previous existing tools in that it can be used in both individuals who are not tube fed, as well as in those who are, as well as across the life-span.

A case report and literature review: Factitious disorder imposed on another and malingering by proxy.

Factitious disorder imposed on another (FDIA) and malingering by proxy (MAL-BP) are two forms of underreported child maltreatment that should remain on physicians' differential. This case of a 2-year-old boy, which spans 6 years, reveals the complexity in and difficulties with diagnosis. Key features include the patient's mother using advanced medical jargon to report multiple disconnected concerns and visits to numerous providers. As a result, the patient underwent many investigations which often revealed normal findings. FDIA was suspected by the paediatrician, especially following corroboration with the child's day care and past primary health care provider. This case demonstrates the possible overlap in diagnoses, which are characterized by a lack of consistent presentation and deceitful caregivers, often complicated by true underlying illness. The authors use clinical experience and limited existing literature to empower paediatricians to confidently diagnose and report FDIA and MAL-BP to limit future harm to children.

Gastrointestinal and feeding difficulties in CHARGE syndrome: A review from head-to-toe.

CHARGE syndrome is an autosomal dominant genetic condition that is primarily diagnosed based on clinical features, with genetic testing available for confirmation. The CHARGE mnemonic stands for some of the common characteristics: coloboma, heart defects, atresia/stenosis of the choanae, retardation of growth/development, genitourinary anomalies, and ear abnormalities (CHARGE). However, many of the common clinical features are not captured by this mnemonic, including cranial nerve dysfunction, considered by some to be one of the major diagnostic criteria. Over 90% of individuals experience feeding and gastrointestinal dysfunction, which carries great morbidity and mortality. The aim of this review is to examine the nature of gastrointestinal (GI) symptoms and feeding difficulties in CHARGE syndrome, focusing on their underlying pathology, associated investigations, and available treatment options. We also provide information on available tools (for parents, clinicians, and researchers) that are important additions to the lifelong healthcare management of every individual with CHARGE syndrome. We review how cranial nerve dysfunction is one of the most important characteristics underlying the pervasive GI and feeding dysfunction, and discuss the need for future research on gut innervation and motility in this genetic disorder.

Guidelines in CHARGE syndrome and the missing link: Cranial imaging.

"CHARGE syndrome" is a complex syndrome with high and extremely variable comorbidity. As a result, clinicians may struggle to provide accurate and comprehensive care, and this has led to the publication of several clinical surveillance guidelines and recommendations for CHARGE syndrome, based on both single case observations and cohort studies. Here we perform a structured literature review to examine all the existing advice. Our findings provide additional support for the validity of the recently published Trider checklist. We also identified a gap in literature when reviewing all guidelines and recommendations, and we propose a guideline for neuroradiological evaluation of patients with CHARGE syndrome. This is of importance, as patients with CHARGE are at risk for peri-anesthetic complications, making recurrent imaging procedures under anesthesia a particular risk in clinical practice. However, comprehensive cranial imaging is also of tremendous value for timely diagnosis, proper treatment of symptoms and for further research into CHARGE syndrome. We hope the guideline for neuroradiological evaluation will help clinicians provide efficient and comprehensive care for individuals with CHARGE syndrome.

Botulinum toxin injections into salivary glands to decrease oral secretions in CHARGE syndrome: prospective case study.

CHARGE syndrome is a genetic disorder caused by a mutation in the CHD7 gene on chromosome 8. Major clinical diagnostic criteria for this heterogeneous disorder include ocular coloboma, choanal atresia/stenosis, characteristic external and internal ear abnormalities, and cranial nerve abnormalities. Patients with CHARGE syndrome often have dysphagia and are at high risk for aspiration of both upper and lower gastrointestinal secretions. The following case-report describes the use of Botulinum toxin A (Botox) to reduce excess salivary secretions in a ventilator dependant infant who would have required a tracheotomy. Thereafter, Botox was used regularly (4-5 months) to decrease the salivary secretions. This case-report is unique in that it describes the intermittent and prospective use of Botox to reduce excess salivary secretions and prevent the resulting aspiration-related complications in an infant with CHARGE syndrome.

Cranial nerve manifestations in CHARGE syndrome.

Cranial nerve (CN) anomalies have been regarded as a major criterion for a clinical diagnosis of CHARGE syndrome for some time. However, there have been relatively few studies of the extent of this involvement. A detailed questionnaire (in French or English) was distributed to all physicians who participated in the 2001-2004 Canadian Paediatric Surveillance Program (CPSP), and who identified themselves as caring for an individual with CHARGE syndrome. Clinical data were collected from multiple sources for each individual, including evidence of CN dysfunction. Evidence for CN anomalies recorded by the clinical presentations and evidence from specialized testing, were: weak chewing and/or sucking (CN V), facial palsy (CN VII), sensorineural hearing loss (CN VIII), balance vestibular problems (CN VIII), and swallowing problems (CN IX/X). Data were analyzed as to the frequency of the CN anomalies and compared to the literature. At the time of this study, there were 99 individuals identified with CHARGE syndrome across Canada. The CHARGE syndrome diagnosis was confirmed by geneticists across the country. Gene testing was not available at the time of this study. Of these 92% exhibited symptoms of at least one CN anomaly, and 72% reported involvement of more than one. Isolated CN involvement was rare. Ascertainment was highest for CN IX/X, and lowest for VIII vestibular. The frequency of CN involvement was generally higher than that reported in the literature.

Adolescent and adult issues in CHARGE syndrome.

Very little information has been published about adolescents and older individuals with Coloboma, Heart defects, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies and deafness (CHARGE) syndrome. This paper describes the results of a study that identifies the unique issues faced by adolescents and adults with CHARGE. Descriptive information was gathered from parents of patients with CHARGE, and/or the patients themselves, about their developmental, medical, educational, and social history. The resulting body of information provides important insights into the prognosis and special needs of individuals with CHARGE, as well as further research questions.

Risk factors for poor bone health in adolescents and adults with CHARGE syndrome.

CHARGE syndrome, is associated with genital hypoplasia, feeding difficulties and delayed puberty. In this study we examined the prevalence of risk factors for poor bone health in adolescents and adults with CHARGE. Questionnaires assessing fracture history, dietary intake of calcium and vitamin D, pubertal status and activity level using the Habitual Activity Estimation Scale (HAES) were completed by caregivers. Control data were collected for the HAES. When available, reports from dual-energy X-ray absorptiometry (DEXA) were obtained. Thirty individuals with CHARGE syndrome (n = 15 males; n = 15 females; age range 13 to 34 years; mean age 19.6 years) were recruited. Traumatic bony fractures were identified in 30% of the population. The recommended nutritional intake (RNI) for calcium and vitamin D were not met by 41% and 87% of the population, respectively, and 53% required past tube feeding. Delayed puberty was experienced by 87% with only 4 individuals (2 female, 2 males) having experienced normal puberty. Hormone replacement therapy (HRT) was taken by 33% of females and 60% of males. According to the HAES, adolescents with CHARGE syndrome (13-18 years) were significantly less active than controls. Individuals with CHARGE syndrome age 19 and older were also less active than controls, although this difference was not significant. DEXA scan data was obtained, however, due to small sample size (n = 10) and confounding variables (i.e., short stature, pubertal stage, height, weight), it was difficult to draw meaningful conclusions. Feeding difficulties, inactivity and hypogonadism are predisposing factors for the development of poor bone health among individuals with CHARGE syndrome. Education is necessary to raise awareness regarding the importance of HRT, proper nutrition and weight-bearing activity for healthy bone development and maintenance in individuals with CHARGE syndrome.

CHARGE syndrome.

CHARGE syndrome was initially defined as a non-random association of anomalies (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness). In 1998, an expert group defined the major (the classical 4C's: Choanal atresia, Coloboma, Characteristic ears and Cranial nerve anomalies) and minor criteria of CHARGE syndrome. Individuals with all four major characteristics or three major and three minor characteristics are highly likely to have CHARGE syndrome. However, there have been individuals genetically identified with CHARGE syndrome without the classical choanal atresia and coloboma. The reported incidence of CHARGE syndrome ranges from 0.1-1.2/10,000 and depends on professional recognition. Coloboma mainly affects the retina. Major and minor congenital heart defects (the commonest cyanotic heart defect is tetralogy of Fallot) occur in 75-80% of patients. Choanal atresia may be membranous or bony; bilateral or unilateral. Mental retardation is variable with intelligence quotients (IQ) ranging from normal to profound retardation. Under-development of the external genitalia is a common finding in males but it is less apparent in females. Ear abnormalities include a classical finding of unusually shaped ears and hearing loss (conductive and/or nerve deafness that ranges from mild to severe deafness). Multiple cranial nerve dysfunctions are common. A behavioral phenotype for CHARGE syndrome is emerging. Mutations in the CHD7 gene (member of the chromodomain helicase DNA protein family) are detected in over 75% of patients with CHARGE syndrome. Children with CHARGE syndrome require intensive medical management as well as numerous surgical interventions. They also need multidisciplinary follow up. Some of the hidden issues of CHARGE syndrome are often forgotten, one being the feeding adaptation of these children, which needs an early aggressive approach from a feeding team. As the child develops, challenging behaviors become more common and require adaptation of educational and therapeutic services, including behavioral and pharmacological interventions.

CHARGE syndrome from birth to adulthood: an individual reported on from 0 to 33 years.

CHARGE syndrome was independently reported by Hall [(1979): J Pediatr 95:395-398] and Hittner et al. [(1979): J Pediatr Ophthalmol Strabismus 16:122-128] and was initially considered to be a non-random association between distinct multiple congenital anomalies. It is now considered to be a recognizable syndrome with well-characterized diagnostic criteria and a genetic pathogenesis. We report on a 33-year-old adult male with CHARGE syndrome, with emphasis on the unique medical, behavioral, and psychological issues faced in adulthood. Characteristic facial and ear abnormalities were obvious in early childhood, and bilateral retinal colobomata, left choanal atresia, right congenital hip dislocation, and hypogonadism were diagnosed during the first year. Walking was delayed due to vestibular problems, speech was impaired due to moderately severe hearing loss, and use of sign communication was limited. Choanal atresia was surgically corrected in infancy, and atrial septal defect, ventricular septal defect, and patent ductus arteriosus were surgically corrected in childhood. Undescended testes were removed in adolescence, and gallstones were removed in early adulthood. Puberty was delayed until hormone replacement therapy began at 15 years. Behavioral disturbances and anxiety persisted throughout childhood, adolescence, and into adulthood, often resulting from communication challenges. At 33 years of age, he lives independently in a supervised group home, receives regular eye check-ups and is being monitored for severely reduced bone density.

An epidemiological analysis of CHARGE syndrome: preliminary results from a Canadian study.

CHARGE syndrome is a well-characterized clinical diagnosis with recent data supporting a genetic etiology. A 3-year national surveillance coordinated by the Canadian Pediatric Surveillance Program (CPSP) was started in September 2001. Physicians notified the CPSP if they had cared for individuals with CHARGE syndrome within their practice, and then completed a detailed reporting form. To date, there are 77 confirmed cases of CHARGE syndrome. The highest provincial prevalence of CHARGE syndrome in Canada was estimated at 1 in 8,500 live births. Subgroups of cases with particular clusters of anomalies were identified. In older individuals, bilateral posterior choanal atresia (BPCA) was predictive of the presence of the three other major criteria and of aortic arch anomalies. Individuals with CHARGE syndrome who demonstrated a less extensive phenotype (