Low CD4+ T-cells

Low CD4+ T-cells. T-cell deficiency, Humoral deficiency, Antibody deficiency INTRODUCTION The CHARGE association (Coloboma of the eye, Heart anomalies, choanal Atresia, mental Retardation, poor growth, Genitourinary and Ear anomalies) includes a group of non-randomly associated anomalies in patients with normal chromosomes. The NGI-1 CHARGE association components and their frequency are listed in table 1.1C3 Other CHARGE association findings include tracheoesophageal fistula, gastroesophageal reflux, dysphagia, facial palsy, micrognathia, cleft lip/palate, central nervous system malformations, ocular hypertelorism, microcephaly, omphalocele, rib anomalies and cranial nerve anomalies such as optic nerve malformations and ptosis.4C6 The CHARGE association is defined as an axial mesodermal dysplasia. This wide spectrum of disorders includes entities with similarities in their phenotypes, such as DiGeorge sequence, 22q11 deletion syndrome, Fanconi anemia, VATER association, Holt-Oram syndrome, thrombocytopenia-aplastic radius syndrome, trisomy 13, etc.7 The overlap among the features of these disorders is large enough to present major diagnostic challenges, and often long-term follow-up is necessary to establish a diagnosis in patients with atypical presentation.8,9 Table 1 Features of CHARGE association.? Colobomatous malformations(80%)Range from isolated iris coloboma without visual impairment to clinical anophthalmos.Retinal colobomas are the most common malformations.Heart defects(80%)Tetralogy of Fallot, patent ductus arteriosus (PDA), ventricular septal defect, atrial septal defect, right-sided aortic arch.Atresia choanae(58%)Membranous and/or bony.Growth deficiency(87%)Usually IL1-BETA postnatal.Developmental delay(100%)Ranges from mild NGI-1 to profound.Genital hypoplasia(75%)Incomplete pubertal development.In males: micropenis, cryptorchidism.In females: hypoplastic labia.Ear anomalies/deafness(90%)Range from small ears without malformation of the pinna to cupshaped ears. Deafness may be either sensorineural (VIII) or mixed sensorineural and conductive, ranging from mild to profound.Cranial nerve dysfunction(70C90%)Anosmia (I), facial palsy, ptosis (VII), swallowing problems (IX, X).Renal anomalies(15C25%)Renal dysgenesis, ectopic/horseshoe kidney, hydronephrosis. Abdominal defects (15%) Inguinal hernia, omphalocele (rare).Abdominal defects(15%)Inguinal hernia, omphalocele (rare).Occasional findingMicrognathia, cleft lip/palate, ocular hypertelorism, microcephaly DiGeorge sequence, tracheoesophageal fistula, anal atresia/stenosis, rib anomalies, hand anomalies, scoliosis, hemivertebrae. Open in a separate window ?Adapted from Smith’s Recognizable Patterns of Human Malformation. Frequency of findings in parentheses.1,2 CASE 1 (IgG2 SUBCLASS DEFICIENCY) Patient 1 presented at 30 months of age. Her diagnosis of CHARGE association was made by a clinical geneticist based on retinal colobomas, choanal atresia, malformed ears with cochlear abnormalities, patent ductus arteriosus (PDA), severe gastroesophageal reflux, poor height gain in spite of normal length at birth and mild mental retardation. Karyotype and fluorescent in situ hybridization for 22q deletion were normal. Patient 1 presented with a history of recurrent respiratory infections. She had nine episodes of bronchiolitis and/or pneumonia in the past 12 months. She also had a large number of ear infections and required two sets of pressure equalization tubes. Rhinoscopy revealed narrowing of nasal passages. The patient also had a history of urticaria and eczema, and positive skin tests for dairy products and soy. Her past medical history included severe gastrointestinal reflux, Nissen fundoplication, and PDA ligation at birth. On physical exam, the patient’s vital signs were normal. Height at 32 months of age was 83 cm, which is below the 5th percentile (height age = 20 months). Height increased over the following 6 months parallel to the 5th percentile. Weight was 12 kg, which was between the 10thC25th percentile for age. Ear exam revealed absent anthelices and canals rotated downward. Pressure equalizing NGI-1 tubes were present on both sides. Oropharyngeal exam showed high palate. Tonsils were present. Neck exam was normal. Chest inspection was significant for PDA repair scar. Heart exam showed a regular rate and rhythm with no murmurs. The abdomen was soft. The liver and.