Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Eye and Systemic Disease_Wright, Spiegel, Thompson_2006

represent 10% of the total group.205 The frequency of the total group is estimated about 1 in 5600 population with a 3:2 male- to-female ratio.85,86

SYSTEMIC FINDINGS

The phenotypic spectrum is large and extremely variable. Unilateral facial involvement (usually the right side) or marked asymmetry is present in about 70% of cases.85 The mandibular ramus and condyle are frequently severely involved.

Ear malformations range from anotia to only ear tags, with intermediate malformations involving size, position, or configuration (Fig. 4-11). Hearing loss may be caused by inner, middle, and external ear lesions. Preauricular tags are present in 40% cases and may be bilateral even in patients in whom the condition appears to be unilateral. Supranumerary tags usually follow an imaginary line extending from the tragus of the ear to the corner of the mouth. Preauricular pits may be present.

Central nervous system anomalies occur in 5% to 15% of cases,5,48,213 and cranial nerve involvement of the trigeminal and facial nerves occurs in 10% to 20% of cases.85 Autism has been reported.132

Cervical spine anomalies also vary widely and include fusional defects, spina bifida, Klippel–Feil anomalies, and scoliosis. The combined presence of this group of malformations occurs in about 55% of cases.85

Macrostomia is common, especially in patients with mandibular malformations and, to a lesser extent, epibulbar dermoids.85 Cleft palate and occasionally cleft lip and dental anomalies are also seen.

Heart, lung, and kidney malformations are reported in 5% to 50% of cases48 but less frequently than in the craniofacial anomalies.

OCULAR FINDINGS

The designation of Goldenhar’s syndrome implies epibulbar or conjunctival lipodermoids with vertebral anomalies in addition to other characteristic findings. Ocular findings are thus more prevalent in this variant.

Ocular and adnexal findings were reported by Hertle et al.102 in 67% of cases in a facial microsomia series, with ptosis or a narrow palpebral fissure on the affected side in 10% of cases. Epibulbar dermoid and conjunctival lipodermoids occur fre-

B

FIGURE 4-11B. (continued).

quently15 and most often inferotemporally. Conjunctival lipodermoids may be inconspicuous. Upper lid colobomas are noted in about 20% of cases.15 There appears to be a higher incidence of associated anophthalmia in cases with severe central nervous system anomalies.85 Hertle et al.102 reviewed 49 cases of facial microsomia (5 bilateral, 44 unilateral); visual loss was noted in 8% of cases, amblyopia in 16%, refractive errors in 27%, and strabismus in 22%.

Strabismus is usually comitant, but there is an increased occurrence of Duane’s syndrome15,154,155,185 and other incomitant types of strabismus.4 Low-incidence anomalies include uveal colobomas,15 corneal anesthesia and corneal ulcers,166,217,244,250 iris coloboma,68 optic nerve hypoplasia, and retinal abnormalities.144

PATHOGENESIS

Branchial arch anomalies are believed to represent a nonspecific syndrome complex due to multiple etiologies and are pathogenetically heterogeneous.85 Poswillo188 believed that vascular disruption in the region of the developing ear and jaw was the initiating cause. Such disruption may cause a local disturbance or may affect migrating neural crest cells.

GENETICS

Most cases are sporadic, with rare concordance in monozygotic twins and a few reported families with characteristics of this heterogeneous complex.205 A similar phenotype has been observed in a few children with chromosomal anomalies, teratogenic causes, and amniotic band syndrome. Genetic counselors estimate a 2% to 3% empirical recurrence risk for future siblings in families with apparently isolated cases.205 Kaye et al.117 analyzed the families of 74 probands by examining relatives to identify ear malformations, mandibular anomalies, and other craniofacial abnormalities. They concluded that the hypothesis of no genetic transmission could be rejected; the evidence favored autosomal dominant inheritance, whereas recessive and polygenic models were not distinguishable.

ROLE OF THE OPHTHALMOLOGIST

Cosmetic and functional ocular malformations are common but extremely variable. In a few patients, the most important challenge may be cosmetic, with anophthalmia or microphthalmia. Many patients require routine treatment of refractive errors, amblyopia, and strabismus. If corneal sensation is decreased, artificial tears may be indicated.

Epibulbar dermoids may result in astigmatism in the affected eye, and treatment should address amblyopia and cosmetic appearance. Small, epibulbar dermoids and many conjunctival lipodermoids require only observation unless they increase in size. If surgical removal is necessary, care should be taken, as symblepharon formation may occur; removal is usually best limited to a readily visible section.152 After removal, the astigmatism often changes only slightly. If the posterior aspect of a large lipodermoid is not visible, radiographic imaging may determine the extent of the lesion.

FETAL ALCOHOL SYNDROME

A pattern of malformations has been observed in children born to women who have a history of alcohol abuse during pregnancy. These dysmorphic features, along with other symptoms and signs, have been designated the fetal alcohol syndrome (FAS).114,116 Recognition of the spectrum of features of this syndrome and insight into the probable prevalence in the general population have emerged during the past two decades, but the observation that the ingestion of large amounts of alcohol by women during pregnancy may result in harm to the fetus has been known for centuries.240,249

This pattern of anomalies in children with typical FAS results in a recognizable gestalt (Fig. 4-12). At the other end of

FIGURE 4-12. Fetal alcohol syndrome: note telecanthus, asymmetrical ptosis, and strabismus.

the spectrum are mildly affected children with fetal alcohol effects (FAE) who may manifest an assortment of malformations. Alcohol-related birth defects (ARBD) is a term used to describe these varied effects.

It is difficult to determine the exact incidence of FAS, FAE, or ARBD, but estimates range from 1 or 2 live births in 1000 to partial expression in up to 3 to 5 in 1000.32 If the 2 in 1000 statistic is accurate, then FAS ranks among the top three causes of mental retardation and is the most preventable. Other studies have suggested that 1 in 30 women abuse alcohol during pregnancy and that 6% of their offspring show noticeable effects. If true, this would make FAS one of the leading causes of mental retardation worldwide.32

The critical amount of alcohol required to produce FAS or any malformation in the fetus or functional effects has not been established, but a definite risk of developing the syndrome is believed to exist with an intake of 89 ml per day of absolute alcohol (average of six drinks).32 Intake of lesser amounts of alcohol (e.g., two drinks per day) carries no established risks but is believed to cause an increased incidence of fetal anomalies. For some malformations, there may be no safe level of alcohol consumption, and binge drinking may result in a malformation even if the average number of drinks consumed per week is

low.88,97,222

CLINICAL MANIFESTATIONS

The typical clinical findings of FAS include (1) facial abnormalities consisting of palpebral fissure changes, thin vermilion border of the upper lip, flat philtrum, and epicanthal folds; (2) mental retardation, varying from mild to severe; (3) low weight and decreased body length at birth and persisting into childhood; and (4) abnormalities of the cardiovascular and skeletal systems (see Fig. 4-12).

Numerous abnormalities of the central nervous system have been described, including abnormal corpus callosum and polymicrogyria.81 Some anomalies implicate abnormal neural migration.85 Holoprosencephaly has also been reported as a possible result of in utero alcohol exposure in both human and mouse studies.227

Alcohol is a well-established behavioral teratogen.222 Children with FAS are frequently hyperactive, show poor motor

ables and dosage and timing of intake variables.2 If the mother does not change her drinking habits, subsequent pregnancies will also have an increased risk of FAS or fetal alcohol effects, but no absolute number can be applied because of the many variables.

ROLE OF THE OPHTHALMOLOGIST

Every child suspected of having FAS or fetal alcohol effects should undergo a complete eye examination to detect the ocular manifestations that could result in severely reduced visual acuity. Treatment of the most common problems, such as refractive errors, strabismus, and amblyopia, should follow standard practices. If the child is in an undesirable socioeconomic environment, compliance with treatment may be poor. The visual potential of the child should be conveyed to the educational authorities for appropriate school placement. Severe ocular malformations, such as Peters’ anomaly, may require extensive and prolonged therapy, and the ophthalmologist becomes an indispensable member of the team to assist in establishing treatment priorities.

HALLERMANN–STREIFF SYNDROME (FRANÇOIS DYSCEPHALIC SYNDROME, OCULOMANDIBULODYSCEPHALY)

Although Hallerman–Streiff syndrome (HSS) had been described previously in the literature, in 1960 François74 published a detailed review and delineation of the characteristic features of this syndrome. Ophthalmologic findings are present in most cases6,28,67,72,221,229 and frequently require surgical and medical treatment. The risks of anesthesia are increased because of obstruction of the upper airways, and this must be considered if early surgery is necessary to remove the congenital cataracts.

SYSTEMIC FINDINGS

Dyscephaly, small stature, dental anomalies, and hypotrichosis occur in 80% to 100% of affected individuals. Final adult height is usually 2 to 5 standard deviations below the mean.85 Prematurity is noted in about one-third of affected individuals, with normal birth weight in two thirds of cases.22 The face is small, with a pointed, thin, pinched nose. The mandible is hypoplas-

A

FIGURE 4-14A,B. Hallermann–Streiff syndrome: characteristic findings of alopecia, small pinched nose, small stature, hypoplastic mandible. (A) Frontal view. (B) Side view.

tic, with displacement of the temporomandibular joint (Fig. 4-14). A double chin with a central cleft and high-arched palate is noted in all cases, and absent teeth and malocclusion are common. Mental retardation has been reported in about 15% to 33% of cases.22,85

The typical finding of alopecia may be missed if the patient is wearing a wig. Occasionally, the thickness of the hair is normal but the hair structure is abnormal.82 Cutaneous atrophy is present in most cases. Cohen34 warned of the potential complications related to the narrow upper airway for anesthesia and sedation.209 Snoring and/or daytime hypersomnolence are indications for sleep studies. Robinow200 also emphasized the risks