The prevalence of autistic disorder was analysed in 25 individuals with Möbius sequence, a disorder with brain-stem dysfunction. The sample consisted of 18 males and seven females (20 participants were aged 2 to 22 years, and five were aged 1, 19 and 23 months, and 55 years old). Participants were recruited after a nationwide call and were part of a multidisciplinary study of individuals with Möbius sequence. They were given a meticulous neuropsychiatric examination including standardized autism diagnostic interviews. Ten individuals had an autistic spectrum disorder. Six of these met all diagnostic criteria for autism. In 23 individuals cognitive development could be assessed. Eight of those 23 patients had clear learning disability and six individuals were functioning in the normal but subaverage range. Autistic spectrum disorder and learning disability occurred in more than a third of the examined patients. Considering the hospital-based nature of the sample, these findings may be overestimates. Nevertheless, awareness of this coexistence is important in the diagnosis and habilitation care of children with Möbius sequence. Moreover, the results provide further support for the notion of a subgroup of autistic spectrum disorders being caused by first trimester brain-stem damage.
BACKGROUND. The eye is a sensitive indicator of adverse effects of prenatal alcohol exposure. Anomalies of the eyes and their adnexa are known to be associated with the fetal alcohol syndrome (FAS), although long-term effects of these malformations are unknown. DESIGN. A prospective ophthalmologic follow-up (median, 11 years; range, 4 to 19 years) was performed in 25 children with FAS. Their social situation and educational status were also investigated. RESULTS. All but one of the children had ophthalmologic abnormalities. Fundus anomalies were observed in 23 children, of whom 19 had optic nerve hypoplasia. Thirteen children had concomitant strabismus. Microphthalmos, buphthalmos, phthisis, microcornea, coloboma of the iris and uvea, blepharoptosis, cataract, persistent hyperplastic primary vitreous, and nystagmus were observed in single cases. The dysmorphology of the eyes remained unchanged during the follow-up period. In 2 children with severe mental retardation and, initially, very poor vision, the severe visual handicap persisted. Seventeen children had an initial visual activity > or = 20/70, which remained unchanged in 10 children and improved in 7 children, despite the presence of optic nerve hypoplasia in 14 of the children. Ten mothers died, 8 of them because of alcohol-related diseases, and only 4 of the mothers were able to take care of their children. Sixteen children went to schools for the mentally retarded, and only 3 children had a normal school education without extra teaching assistance. CONCLUSIONS. In children with FAS, the major sequela, ie, brain, damage, remains despite extensive medical, educational, and social support. The presence of ophthalmic signs, which persisted but did not deteriorate during the follow-up period, strengthens the diagnosis of FAS, and the high frequency of ocular involvement indicates the importance of a complete ophthalmologic evaluation in children with FAS.
BACKGROUND: The constellations of findings often referred to as Mobius syndrome might be better described as Mobius sequence, because the term sequence defines a cascade of secondary events after an embryonic insult from heterogeneous causes. Classic clinical findings include evidence of sixth and seventh cranial nerve involvement, often with associated malformations of limbs, craniofacial structures, and other cranial nerves. METHODS: A prospective study was undertaken in Sweden of 25 patients who showed characteristic findings of Mobius sequence. RESULTS: Of the patients who did not have strabismus surgery, 10 patients had straight eyes in the primary position, 7 had esotropia, 2 had exotropia, and 1 had hypertropia. All had significant limitation of abduction, except 1 patient with exotropia who showed minimal underaction on abduction but a large limitation of adduction. In the description in these early cases, some patients manifested a clinical pattern resembling a horizontal gaze paresis. Narrowing of the palpebral fissure on adduction similar to that seen in Duane syndrome was observed in a few cases. Two patients had ptosis. Nineteen patients had diminished facial expression bilaterally, often asymmetric, and 6 cases appeared to be unilateral. Seven patients had abnormal tearing. Associated systemic findings included Poland anomaly (2), club feet or other limb anomalies (8), micrognathia (8), tongue malformations (17), cleft palate (5), and speech problems (18). An unusual finding was autism syndrome (6) or autism-like syndrome (1). CONCLUSIONS: The associated findings in Mobius sequence may give further clues to the location and timing of the developmental disturbance. The wide range of ocular motility patterns suggests that the previous concept of a lesion solely in the sixth nerve nucleus is an inadequate explanation for these findings.
Twenty-one individuals, aged 28 to 29 years, with documented thalidomide embryopathy were examined in Sweden. The most noteworthy ophthalmologic finding was the high prevalence of incomitant horizontal strabismus, primarily of the Duane syndrome type. Less frequently seen were cases of both marked abduction and adduction limitation similar to a gaze paresis with no observable fissure changes, as well as a few cases of isolated abduction weakness or inferior oblique under-action. There were many examples of aberrant lacrimation, facial nerve palsy, and ear anomalies combined with horizontal incomitant forms of strabismus. Ear and facial nerve palsies are known to occur with ingestion of thalidomide early in the sensitive period (approximately days 21 to 26 after conception).
OBJECTIVE: To investigate whether children with optic nerve hypoplasia and pituitary hormone insufficiencies have specific ocular fundus characteristics that may facilitate early diagnosis and treatment. DESIGN: From May 15, 1995, through December 15, 1997, 17 children (8 girls and 9 boys, aged 0.3 to 13 years) with optic nerve hypoplasia were referred to the Department of Pediatric Ophthalmology, Children's Hospital, Göteborg, Sweden, and divided into 2 groups dependent on the presence (n = 8) or absence (n = 9) of pituitary deficiency. Morphological characteristics of the ocular fundus were evaluated by digital image analysis of fundus photographs, and the morphological characteristics of the brain structures were studied by magnetic resonance imaging. RESULTS: An isolated venous tortuosity noted among the children with optic nerve hypoplasia and endocrinopathy was the morphological ocular fundus variable that discriminated between the 2 groups of patients with optic nerve hypoplasia. Both groups of children demonstrated significantly reduced optic disc, cup, and neuroretinal rim area and few vascular branching points. CONCLUSION: Optic nerve hypoplasia with isolated tortuosity of the retinal veins may potentially help the ophthalmologist in identifying children who should undergo a thorough diagnostic workup of endocrine function.
Our study of individuals with thalidomide embryopathy reaffirms many of the principles of clinical teratology concerning sensitivity of developing structures and specificity of action. It also highlights important features of ocular teratology that differ from those of other organ systems. Because malformations of the eye and associated structures do not significantly threaten the survival of the embryo, fetus, or neonate, any variation in prevalence in older individuals is not due to the nature of the ocular malformation but may be significantly modified by "the company they keep," the systemic malformations occurring at the same time as the original insult, whether it be an environmental, a genetic, or a local disturbance. Additionally, the presence of clusters of malformations caused by a teratogen at a specific time supports the concept of a common pathogenic mechanism and provides suggested avenues for further research into the cause of these malformations.
Cites: Trans Am Ophthalmol Soc. 1991;89:623-741808819
A prospective ophthalmological study was done in 86 out of a total of 100 Swedes with established thalidomide embryopathy. Forty-six (54%) of all examined individuals had eye findings, which made the eye the second most commonly affected organ in thalidomide embryopathy only surpassed by upper limbs (81%). Forty-three patients (50%) had ocular motility defects, mostly incomitant strabismus. Facial palsy and abnormal lacrimation each occurred in 17 (20%) individuals. One patient had coloboma of the uvea and optic disc and another two had coloboma of the optic disc. Infrequent anomalies were microphthalmos, congenital glaucoma, lipodermoid, and large refractive errors. The observed ocular motility defects, facial palsy and abnormal lacrimation occurred with early induced defects in thalidomide embryopathy, but not with isolated late occurring anomalies. This suggests that thalidomide exerts its effects on the development of these structures early in the teratogenic period, probably mainly during the fourth week of development.
AIMS: To evaluate ophthalmological findings in children adopted from eastern Europe. METHODS: A prospective study on 72/99 children, born 1990-5 and adopted from eastern Europe to western Sweden during 1993-7 was performed. The children (41 boys; mean age 7.5 years) were compared with an age and sex matched reference group ("ref") of Swedish children. RESULTS: 78% of the adopted children had abnormal ocular findings. 26% (ref 4%) had visual acuity (VA) of the better eye or = 0.3 logMAR) (p = 0.0001) and 8% (ref 0%) were visually impaired (p = 0.01). Amblyopia was found in 15% (ref 2%) (p = 0.005). 22% (ref 10%) were hyperopic (> or = 2.0 D SE) (NS) and 10% (ref 1%) were myopic (> or = 0.5 D SE) (p = 0.03). Astigmatism (> or = 0.75 D) was found in 51% (ref 23%) (p = 0.004). 32% (ref 2%) had strabismus (p