Table 2 Clinical and genetic features
From: A case series of CHARGE syndrome: identification of key features for a neonatal diagnosis
Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Prevalence of clinical features | ||
|---|---|---|---|---|---|---|---|---|---|---|
In our patients | In the literature8 | |||||||||
Presenting feature | Esophageal atresia with fistula | Cleft lip and palate | Double outlet right ventricle, pulmonary valve stenosis, VSD, ASD | Blefarofimosis with microphthalmia and cyst, esophageal atresia with fistula | Axial hypotonia and hypertonia of extremities | Difficulty in sucking | Esophageal atresia with fistula | Difficulty in swallowing | NA | NA |
Ocular defects | Bilateral chorioretinal coloboma | Bilateral chorioretinal coloboma | Bilateral chorioretinal coloboma | Bilateral coloboma, left blefarofimosis with microphthalmia and cyst | Bilateral chorioretinal coloboma | Left chorioretinal coloboma | Left chorioretinal coloboma | None | 7/8 | 80–90% |
Choanal atresia | No | No | No | Yes | No | No | No | No | 1/8 | 50–60% |
Outer ear anomalies | Squared ears absent lobules | Low set ears with antihelix anomalies | Dysplasia of ear pads | Low set squared ears | Dysplasia of ear pads, small lobules | Dysplasia of ear pads | Squared ears absent lobules | Low set ears with small lobules | 8/8 | 80–100% |
Middle ear anomalies | Ossicular malformation and right stenotic oval window | None | None | Right stapes and incus malformation and stenotic oval window | Bilateral stapes and incus malformation and atretic oval window | None | Right atretic oval window | Dysplasia of the stapes and of the oval window | 5/8 | 80–100% |
Inner ear anomalies | Bilateral hypoplasia of SCC and vestibulum and cochlear malformation (incomplete partition type II) | Right aplasia of superior and lateral SCC and hypoplasia of left superior and lateral SCC and bilateral posterior SCC. Left vestibular enlargement Bilateral cochlear malformation (incomplete partition type II) Bilateral stenotic Rosenthal’s canal | Bilateral absence of semicircular canals, bilateral cochlear malformation and vestibular dysplasia | Bilateral aplasia of SCC, Right cochlear malformation (incomplete partition type II) and vestibular dysplasia. Right stenotic Rosenthal’s canal | Bilateral absence of SCC, vestibular and cochlear malformation (incomplete partition type II). Bilateral aplasia of Rosenthal’s canal | Bilateral hypoplasia of lateral SCC and aplasia of posterior SCC | Bilateral aplasia of SCC | Bilateral aplasia of superior and posterior SCC, dysplasia of lateral SCC and vestibulum Abnormal right vestibular enlargement | 8/8 | 80–100% |
Heart defects | ASD | Pulmonary valve stenosis | Double outlet right ventricle, pulmonary valve stenosis, VSD, ASD | VSD | ASD and PDA | Pulmonary valve stenosis | None | None | 6/8 | 75–85% |
Tracheoesophageal anomalies | Esophageal atresia with fistula | None | None | Esophageal atresia with fistula | None | None | Esophageal atresia with fistula | None | 3/8 | 15–20% |
Lip, palate, pharynx, larynx | None | Cleft lip and palate | None | None | Velopharingeal insufficiency, hypotonia of vocal cord | None | None | Severe laryngomalacia and tracheomalacia | 3/8 | 15–20% |
Genital anomalies | None | None | None | Genital hypoplasia | None | Imperforate hymen | None | Micropenis, cryptorchidism, | 4/8 | 50–60% |
Renal anomalies | Multicystic left kidney | None | None | None | None | None | None | Horseshoe kidney | 2/8 | 25–40% |
Brain anomalies | Cerebellar vermis hypoplasia | Cerebellar vermis hypoplasia | None | Cerebellar vermis hypoplasia | Axial hypotonia and hypertonia of extremities | None | Cerebellar and pons hypoplasia | Hypotonia | 6/8 | NA |
Cranial nerve anomalies | Hypoplasia of the olfactory bulbs, hypoplasia of optic nerves, bilateral neurosensorial hearing loss | Hypoplasia of the olfactory bulbs, bilateral neurosensorial hearing loss | Left laryngeal hemiplegia, peripheral paralysis of left facial nerve, deficit in swallowing, bilateral neurosensorial hearing loss | Agenesis of olfactory bulbs, hypoplasia of left optic nerve and of left part of optic chiasm, right aplasia of superior vestibular nerve | Agenesis of olfactory bulbs, hypoplasia of optic nerves, aplasia of vestibular nerves, bilateral neurosensorial hearing loss | Agenesis of olfactory bulbs, hypoplasia of optic nerves, bilateral, right cochlear nerve aplasia, neurosensorial hearing loss, deficit in swallowing and sucking | Hypoplasia of left olfactory bulbs, hypoplasia of optic nerves, deficit in swallowing | Depressor oris, deficit in swallowing, agenesis of olfactory right bulb, hypoplasia of optic nerves, left cochlear nerve aplasia, left neurosensorial hearing loss | 8/8 | 70–90% |
Genetic tests performed before CHD7 analysis | Karyotype in prenatal period | None | Karyotype array-CGH in prenatal period | None | None | None | None | FISH for 22q11.2, array-CGH, targeted NGS panel for Kallmann S. | NA | NA |
CHD7 mutation | c.2867C > A; p.Ser956X unknown origin parents not available | c.8745–8746 insA fs2948X unknown origin parents not available | c.2429 C>G;p.Ser810Xfather wt; mother not available | c.5428C>T;p.Arg1810Xde novo origin | c.1465 C > T; p.Gln489X de novo origin | c. 5050 A > G; p.Gly1684Ser de novo origin | c.5884 G > A p.Gly1802Asp de novo origin | c.5405-17G > A; IVS25 de novo origin | NA | NA |