Ophthalmic features of CHARGE syndrome with CHD7 mutations

Abstract

Coloboma and various ocular abnormalities have been described in CHARGE syndrome, although the severity of visual impairment varies from case to case. We conducted a multicenter study to clarify the ophthalmic features of patients with molecularly confirmed CHARGE syndrome. Thirty-eight eyes in 19 patients with CHARGE syndrome and confirmed CHD7 mutations treated at four centers were retrospectively studied. Colobomata affected the posterior segment of 35 eyes in 18 patients. Both retinochoroidal and optic disk colobomata were bilaterally observed in 15 patients and unilaterally observed in 3 patients. The coloboma involved the macula totally or partially in 21 eyes of 13 patients. We confirmed that bilateral large retinochoroidal colobomata represents a typical ophthalmic feature of CHARGE syndrome in patients with confirmed CHD7 mutations; however, even eyes with large colobomata can form maculas. The anatomical severity of the eye defect was graded according to the presence of colobomata, macula defect, and microphthalmos. A comparison of the severity in one eye with that in the other eye revealed a low-to-moderate degree of agreement between the two eyes, reflecting the general facial asymmetry of patients with CHARGE syndrome. The location of protein truncation and the anatomical severity of the eyes were significantly correlated. We suggested that the early diagnosis of retinal morphology and function may be beneficial to patients, since such attention may determine whether treatment for amblyopia, such as optical correction and patching, will be effective in facilitating the visual potential or whether care for poor vision will be needed.

CHD7 Deficiency in “Looper”, a New Mouse Model of CHARGE Syndrome, Results in Ossicle Malformation, Otosclerosis and Hearing Impairment

“…In contrast, Looper mice display blepharoconjuctivitis, which may indicate increased susceptibility to infection or structural changes of the eye socket and lid. Bilateral asymmetry of Looper eye phenotypes correlates with CHARGE, but blepharoconjunctivitis does not [32]. Furthermore, ocular coloboma, one of the major diagnostic features of CHARGE was not observed in Looper mice.…”

Systemic Abnormalities in Children with Congenital Optic Disc Excavations

“…The optic disc coloboma may be associated with a coloboma involving the retina, the ciliary body, or the iris. The defect, which can be sporadic or inherited, 12,13 has been associated with several polymalformative syndromes, including the Charge syndrome, 14 renal coloboma syndrome, 15 Aicardi syndrome, 16 Solomon's syndrome, 17,18 or Noonan syndrome. 19 Optic disc excavations may also be consecutive to optic nerve compression, intracranial hypertension, or periventricular leukomalacia.…”

Defects in Thymic Development

“…6 These findings are mostly limited to the group with 22q11.2DS. 110 The colobomas may or may not involve the macula. The coloboma are usually retinochoroidal and involve the optic disc.…”

“…37 A major criterion for diagnosis of CHARGE syndrome is ocular coloboma. 110 Microphthalmos is seen in approximately one-quarter of patients. 110 The colobomas may or may not involve the macula.…”

“…The coloboma are usually retinochoroidal and involve the optic disc. 110 Ear anomalies and hearing deficits are very common in 22q11.2DS and CHARGE syndrome. 110 Microphthalmos is seen in approximately one-quarter of patients.…”