[source]
pmid = PMID:17661815
title = Familial CHARGE syndrome because of CHD7 mutation: clinical intra- and interfamilial variability
[diagnosis]
disease_id = OMIM:214800
disease_label = CHARGE syndrome
[text]
Patient A III-2 is the second boy of non-consanguineous French parents, respectively, aged 30 and 29 years, at the time of conception.
The pregnancy was characterized by polyhydramnios from the 26th week of gestation.
Delivery took place after 38 weeks by caesarean section with normal birth weight (BW) (3025 g, 50th centile), birth length (BL)
(48 cm, 25th centile) and head circumference (OFC) (34.5 cm, 50th centile). MCA noted at birth included esophageal atresia with tracheoesophageal fistula,
bilateral cleft lip and palate, large ventricular septal defect, dextroposition of aorta, atresia of the brachiocephalic trunk,
malacia of the right main bronchus, costovertebral abnormalities (bifid fourth dorsal vertebrae, duplication of the fourth right rib,
and spina bifida occulta from the seventh to the ninth dorsal vertebrae) and left cryptorchidism.
Axial control acquisition was delayed as he sat at the age of 11 months, walked at 22 months.
Balance problems persisted for several years. Recurrent otitis media, responsible for conductive hearing loss,
required bilateral tympanostomy tubes. First words were delayed till 30 months. Learning disabilities and writing difficulties
were confirmed when he was 8 year. When referred to the genetic department at the age of 15 years,
he was 151 cm tall (−2 SD ), weighted 40 kg (−2 SD), and had an OFC of 52 cm (−2 SD).
At that time, he had a long face with prominent chin, small mouth, high nasal bridge and triangular shape of right concha
(Fig. 1). He had postural instability. Vestibular testing showed absence of response on canal function test with residual otolith
function and residual left vestibulospinal responses on vestibular evoked myogenic potential test.
Magnetic resonance imaging (MRI) examination showed hypoplastic superior and lateral semicircular canals (SCC) in the right ear
and aplastic superior and hypoplastic lateral SCC in the left ear (Fig. 2). The vestibulae and the cochleae were normal.
Facial and vestibulo-cochlear nerves were present on both sides. Brain MRI revealed a hypoplastic internal left carotid artery.
There was no evidence for arhinencephaly. He had mild convergent strabismus, discrete myopia and posterior embryotoxon.
Funduscopic examination revealed hypoplastic papillae. Using WISC IV scale at age 15 years his verbal conceptual index (VCI) was 78,
perceptual reasoning index (PRI) 58, working memory index (WMI) 62 and processing speed index (PSI) 81.
[text]
Patient B III-1 is the first child from healthy unrelated Caucasian parents. Mother and father were both 26 years old at time of conception.
Cerebral ventricular dilatation was suspected on pre-natal ultrasound but not confirmed by fetal cerebral MRI.
Fetal karyotype was normal (46, XY). Premature labor occurred and delivery took place at a gestational age of 35 weeks.
BW was 2050 g (third centile); BL 46.5 cm (50th centile) and OFC 34 cm (90th centile). He had cup-shaped ears with missing earlobes,
right facial palsy, bifid uvula and mild retrognathism (Fig. 4) with associated cryptorchidism and global hypotonia.
Swallowing difficulties with poor feeding were noted. Laryngoscopy revealed left vocal cord palsy.
An atrial septal defect was diagnosed by echocardiography. Fundoscopy showed right retinal coloboma.
Brainstem electric response audiometry identified a sensorineural deafness, visual evoked potentials were in the normal range.
Metabolic work-up did not show any anomaly. This boy died on day 19 after refractory convulsive episodes starting on day 4.
Encephalopathy and hydrocephaly were subsequently noted, as post-natal cerebral MRI (day 7) showed quadriventricular enlargement
because of bloody effusion in occipital horns without any underlying vascular malformation. On autopsy,
brain external examination revealed the absence of olfactory bulbs with a thin corpus callosum.
On microscopic exam, cranial nerve roots were normal. Deep cerebellar heterotopia was present.
Complete macroscopic and microscopic examinations were otherwise normal except for the presence of testis in the inguinal canals.