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OBJECTIVES: CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome are known to have significant clinical overlap including cardiac anomalies, ear abnormalities, hearing loss, developmental delay, renal abnormalities, and cleft palate. Immunodeficiency has been well documented in 22q11.2 deletion, but there has been limited recognition of this potentially serious complication in CHARGE syndrome. The goals of our study were to identify clinical features unique to CHARGE syndrome or 22q11.2 deletion and to describe the spectrum of immunodeficiency found in patients with CHARGE syndrome. METHODS: This study included 25 children diagnosed with CHARGE syndrome with positive CHD7 mutations through the Children's Hospital of Philadelphia genetics program. Clinical features and laboratory findings were reviewed retrospectively. We compared our findings to data available for a large cohort of patients with 22q11.2 deletion syndrome followed in our clinical genetics program. RESULTS: Features found more commonly in CHARGE syndrome included coloboma, choanal atresia, facial nerve palsy, tracheoesophageal fistula, and genital hypoplasia in boys. A high incidence of marked hypocalcemia was observed in our study group (72%). We found a spectrum of cell-mediated immunodeficiency in our study group, which ranged from lymphopenia (60%) to severe combined immunodeficiency (8%). Defects in humoral immunity were documented in 4 patients and included severe hypogammaglobulinemia with decreased T-cell numbers, transient hypogammaglobulinemia during infancy, and immunoglobulin A deficiency. CONCLUSIONS: The presence of coloboma, choanal atresia, facial nerve palsy, tracheoesophageal fistula, or genital hypoplasia in boys should alert the clinician to the possibility of CHARGE syndrome rather than the 22q11.2 deletion. Molecular testing for CHD7 mutations may help to confirm the diagnosis. In this study, significant hypocalcemia and lymphopenia occurred more frequently in patients with CHARGE syndrome than in those with 22q11.2 deletion syndrome. Early inclusion of immunologists to the multidisciplinary care team (as with 22q11.2 deletion) may be of great benefit to affected patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Conotruncal cardiac anomalies frequently occur in patients with DiGeorge or velocardiofacial syndrome. Additionally, these patients may have overt or submucousal cleft palate, as well as velopharyngeal incompetence (VPI). Previous studies have demonstrated that the majority of these patients have a submicroscopic deletion of chromosome 22q11.2. We hypothesized that a subpopulation of newborns and children with congenital heart defects caused by a 22q11.2 deletion are at a high risk for having unrecognized palatal abnormalities. Therefore, we proposed to evaluate a cohort of patients with conotruncal cardiac malformations associated with a 22q11.2 deletion to determine the frequency of palatal abnormalities. METHODS: We identified 14 deletion-positive patients with congenital cardiac defects who had no overt cleft palate. Of the 14 patients evaluated for the 22q11.2 deletion, 8 patients were recruited from a previous study looking for deletions among patients with isolated conotruncal cardiac anomalies. Informed consent was obtained in these cases. The remaining patients had the deletion study on a clinical basis, ie, conotruncal cardiac defect and an absent thymus, immunodeficiency, or minor dysmorphia appreciated by the clinical geneticist. These patients were evaluated by a plastic surgeon and speech pathologist looking for more subtle palatal anomalies such as a submucousal cleft palate, absence of the musculous uvuli, and VPI. Some patients underwent videofluoroscopy or nasendoscopy depending on their degree of symptoms and age. VPI was not ruled out until objective evaluation by a speech pathologist and plastic surgeon was obtained. In addition, the child had to be old enough to provide an adequate speech sample. RESULTS: Of the 14 patients evaluated, 6 patients older than 1 year were found to have VPI. It is noteworthy that 3 of these patients were older than 5 years and had remained unrecognized until this study. The remaining 6 patients had inconclusive studies based on their age (younger than 26 months) and their inability to participate in adequate speech evaluations. Two of these patients, however, had histories of nasal regurgitation suggesting VPI and, in addition, had incomplete closure of the velopharyngeal mechanism during crying and swallowing observed during nasendoscopic examination-consistent with the diagnosis of VPI. Thus, 8 of 14 patients evaluated had evidence of VPI by history and examination. The remaining 6 patients will require further study when they are older before a definitive palatal diagnosis can be made. CONCLUSIONS: A significant number of patients with a 22q11.2 deletion in a cardiac clinic may have unrecognized palatal problems. Recognition of such abnormalities will afford patients the opportunity for intervention as needed, ie, speech therapy and/or surgical intervention. Notably, two of our patients with findings suggesting VPI were infants and will, therefore, be afforded the opportunity for close follow-up and early intervention. Furthermore, three school-aged children had palatal abnormalities that were unrecognized until this study. Thus, we recommend 22q11.2 deletion studies in patients with conotruncal cardiac malformations, followed by extensive palatal and speech evaluations when a deletion is present. [ABSTRACT FROM AUTHOR]

Background and Objectives: Telemedicine may increase access to medical genetics care. However, in the pediatric setting, how telemedicine may affect the diagnostic rate is unknown, partially because of the perceived importance of the dysmorphology physical examination. We studied the clinical effectiveness of telemedicine for patients with suspected or confirmed genetic conditions., Methods: We conducted a retrospective cohort study of outpatient encounters before and after the widespread implementation of telemedicine (N = 5854). Visit types, diagnoses, patient demographic characteristics, and laboratory data were acquired from the electronic health record. Patient satisfaction was assessed through survey responses. New molecular diagnosis was the primary end point., Results: Patients seen by telemedicine were more likely to report non-Hispanic White ancestry, prefer to speak English, live in zip codes with higher median incomes, and have commercial insurance (all P < .01). Genetic testing was recommended for more patients evaluated by telemedicine than in person (79.5% vs 70.9%; P < .001). Patients seen in person were more likely to have a sample collected, resulting in similar test completion rates (telemedicine, 51.2%; in person, 55.1%; P = .09). There was no significant difference in molecular diagnosis rate between visit modalities (telemedicine, 13.8%; in person, 12.4%; P = .40)., Conclusions: Telemedicine and traditional in-person evaluation resulted in similar molecular diagnosis rates. However, improved methodologies for remote sample collection may be required. This study reveals the feasibility of telemedicine in a large academic medical genetics practice and is applicable to other pediatric specialties with perceived importance of physical examination., (Copyright © 2022 by the American Academy of Pediatrics.)

The list of findings associated with the 22q11.2 deletion is quite long and varies from patient to patient. The hallmark features include: conoruncal cardiac anomalies, palatal defects, thymic aplasia or hypoplasia, T cell abnormalities, mild facial dysmorphia, and learning disabilities. The 22q11.2 deletion has been seen in association with the DiGeorge sequence, velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome, isolated conotruncal cardiac anomalies, and some cases of autosomal dominant Optiz G/BBB syndrome. Short stature has been seen in one to two thirds of children reported in the literature with a diagnosis of VCFS, but growth hormone deficiency (GHD) has not been described in conjunction with this diagnosis. We present 4 patients with a 22q11.2 deletion and short stature who were found to have abnormalities in the growth hormone-insulin-like growth factor I axis. All had growth factors less than -2 SD for age and failed provocative growth hormone testing. Two patients were found to have abnormal pituitary anatomy. In our population, the incidence of GHD in 4 or 95 children with 22q11 deletion is significantly greater than the estimated incidence of GHD in the general population. Children with a 22q11.2 deletion appear to be at a greater risk for pituitary abnormalities. Therefore, those children with the 22q11.2 deletion and short stature or poor growth should be evaluated for GHD, as replacement growth hormone therapy may improve their growth velocity and final height prediction.