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Treat with low phytol diet (no dark green vegetables), and maintain body weight.

Zellweger syndrome, cerebro-hepato-renal disease: cartilage calcification with joint disorder, nonrecordable ERG, and optic atrophy.

SPHINGOLIPIDOSES Cell membrane components are not degraded but instead accumulate in cells.

Fabry’s disease: X-linked deficiency of alpha-galactosidase; 90% have corneal verticillata, tortuous conjunctival and retinal vessels, and posterior spokelike cataract.

Farber’s disease: deficient ceramidase, with cherry red spot.

Gaucher’s disease: deficient glucocerebrosidase, with choroidal and conjunctival macrophage accumulation.

Krabbe’s disease: deficient galactocerebrosidase beta-galactosidase in 50% of patients, with white matter necrosis and cherry red spot.

Niemann-Pick disease, type B: deficient sphingomyelinase, causing macular halo, hepatosplenomegaly, lung infiltration, bone marrow foam cells, and no mental retardation, unlike the others.

Sandhoff disease: GM2 type II gangliosidosis from deficient hexosaminidase alpha, causing a cherry red spot.

Tay-Sachs disease: GM2 type I gangliosidosis from defect in hexosaminidase beta, with accumulation in ganglion cells (highest concentration in the macula), causing a cherry red spot, mental retardation, and early death.

WAARDENBURG’S SYNDROME Autosomal dominant developmental anomalies of eyelids, nasal root, and eyebrows, with heterochromia iridis, white forelocks, and sensorineural deafness.

Congenital Disease: Phakomatoses

OVERVIEW The word phakomatosis means ‘‘lentil, or a spot on the body,’’ because most disorders have skin findings. Most are hamartoma disorders that are autosomal dominant, except the diseases with W in their names (Sturge-Weber syndrome [SW] and Wyburn-Mason’s syndrome [WM]), which are sporadic, and (ataxia-telangiectasia [AT]), which is autosomal recessive. The diseases with S in their names, Sturge-Weber (SW) and tuberous sclerosis (TS) are characterized by seizures.

ATAXIA-TELANGIECTASIA (AT), LOUIS-BAR SYNDROME Autosomal recessive phakomatosis of abnormal DNA repair from chromosome 11q22.3, causing telangiectasias on the face, neck, and conjunctiva; also has cerebellar ataxia, mental retardation, hypoplastic thymus with recurrent sinopulmonary infections; increased lymphoma, leukemia, and insulin resistance; increased glucose; and no CNS abnormalities.

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NEUROFIBROMATOSIS I, VON RECKLINGHAUSEN’S DISEASE Classical, peripheral, autosomal dominant phakomatosis with variable penetrance from chromosome 17q-defect (mnemonic: 17 letters in neurofibromatosis), characterized by hamartomas of neural crest tissue. Occurs in 1 in 3000 births. Neurofibromas are tumors are from the peripheral nerve sheaths; patients also have CNS tumors such as glioma, meningioma, and increased risk of breast, gastrointestinal, and genitourinary cancers, pheochromocytomas, and cutaneous and uveal melanomas. Diagnosis established by two or more of the following:

Cafe´ au lait spots: six or more >5 mm in children or >15 mm in adults. Pathology shows normal skin except increased pigmentation in the basal layers; present in 99% of NF patients.

Cutaneous neruofibromas: two or more; can degenerate into fibrosarcomas.

Plexiform neurofibroma: may cause S-shaped eyelid; 50% of unilateral upper lid plexiform neurofibromas have ipsilateral glaucoma. May cause significant ptosis.

Axillary or inguinal freckling

ON glioma: 15% prevalence; fusiform ON enlargement. Glioma is actually a JPA.

Absence of sphenoid wing: may cause pulsatile proptosis; may have other osseous deformities.

Lisch nodules: two or more melanocytic hamartomas on the iris; seen in 92% of NF cases. Useful for establishing or excluding the diagnosis because they are not found in normal patients.

Family history: first-degree relative with NF1.

NEUROFIBROMATOSIS II Central phakomatosis with hamartomas of neural crest tissue, from chromosome 22q defect; characterized by CNS tumors such as acoustic schwannoma. Diagnosis needs one of the following:

Bilateral acoustic neuroma

Unilateral acoustic neuroma with first-degree relative affected

Two of the following: meningioma, glioma (15% prevalence, fusiform and kinked appearance on CT), schwannoma, neurofibroma, presenile PSC cataract

Other findings may include pheochromocytoma (15%), Lisch nodules, plexiform neurofibroma, ipsilateral glaucoma with upper lid neurofibroma, prominent corneal nerves, choroidal hamartomas (flat, 51% prevalence), retinal and RPE hamartomas, choroidal melanoma, proptosis from ON glioma, orbital neurofibromas, and sphenoid dysplasia.

ORGANOID NEVUS SYNDROME, NEVUS SEBACEOUS OF JADASSOHN

Alopecia anterior to ear and 20% BCC in that area; associated with

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358 PEDIATRICS AND STRABISMUS

posterior scleral cartilage, epibulbar complex choristomas, seizures, mental retardation, and cardiovascular, renal, hepatic, skeletal abnormalities.

STURGE-WEBER SYNDROME (SW), ENCEPHALOTRIGEMINAL ANGIOMATOSIS Nonhereditary (sporadic) phakomatosis with unilateral facial cutaneous angioma (nevus flammeus or port-wine stain, usually V1-V3 distribution) and choroidal cavernous hemangioma (‘‘tomato catsup’’ fundus). Thirty-three percent of cases have ipsilateral glaucoma when lid or conjunctiva is involved (60% from congenital trabeculodysgenesis and 40% from late-onset increased EVP). Eighty percent have unilateral meningeal hemangioma with contralateral epileptic attacks, mental retardation, and calcification of gyri (‘‘railroad tracks’’ on skull films).

Klippel-Tre´naunay-Weber syndrome: bilateral cutaneous hemangioma with extremity hypertrophy and systemic vascular anomalies.

TUBEROUS SCLEROSIS (TS), BOURNEVILLE’S SYNDROME Autosomal dominant (but incomplete penetrance) phakomatosis, from defect on chromosome 16 (50%) and chromosome 9 (50%), with retinal or ON astrocytic hamartomas (50%), seizures (90%), and mental retardation secondary to CNS astrocytic hamartomas (‘‘tubers’’ or, if calcified, ‘‘brain stones’’). May also have retinal peripheral depigmentation (ash leaf spot equivalent), fine facial acne (adenoma sebaceum, which is really angiofibromas; seen in 83% of cases), skin ash leaf spots (shagreen patches; pathology shows smaller melanosomes with less pigment; seen in 80% of cases) or cafe´ au lait spots, periungual fibromas, renal/pulmonary/bone cysts, and cardiac rhabdomyosarcoma.

VON HIPPEL-LINDAU DISEASE (VHL), ANGIOMATOSIS RETINAE Autosomal dominant phakomatosis, from defect on chromosome 3ptumor supression gene (controls VEGF production; like RB, patients inherit one hit, then acquire second hit), characterized by capillary hemagioblastomas of the retina fed by dilated tortuous artery drained by engorged vein; may have exudative RD. Up to 60% of cases have a cerebellar hemangioblastoma (vertigo, ataxia), 25% renal cell carcinoma (most common cause of VHL deaths; usually about age 50, with 50% mortality; check urinanalysis for hematuria). May also see renal, pancreatic, or hepatic cysts, meningiomas, and pheochromocytomas; no skin involvement like other phakomatoses. May laser small (<2 DD) retinal lesions or cryotherapy larger ones.

WYBURN-MASON SYNDROME (WM), RACEMOSE HEMANGIOMA Sporadic defect of a single AV communication (no capillary bed; also known as congenital retinal macrovessel) with dilated, tortuous retinal vessels; also found in ipsilateral brain, orbit, and face (reported fatal hemorrhage following dental extraction).

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Strabismus: Esotropia

EPIDEMIOLOGY ET comprises 70% of strabismus and may be congenital/ infantile or acquired; most are comitant but may be incomitant.

PSEUDOESOTROPIA Wide nasal bridge, prominent epicanthal folds, or negative angle kappa give the appearance of ET, but patient is aligned on cover testing; recheck patient in 3 months.

CONGENITAL OR INFANTILE ESOTROPIA Large-angle (usually >35 pD) constant ET; onset within 6 months. Patients have normal refraction (þ1.5 D average) and usually alternate/cross-fixate; thus, amblyopia is sometimes seen. ET is horizontally comitant (pD near ¼ distance) and may have effort nystagmus in abduction. Infantile esotropia is characterized by poor abducting kinetics, usually a positive family history, and is genetic; thus, it is more acurately considered a syndrome. MR may be anteroplaced (i.e., 3.5 mm from limbus). Angle may be variable when associated with cerebral palsy.

Differential diagnosis: Duane’s syndrome type I, nystagmus blockage syndrome, Mo¨bius’ syndrome, early-onset accommodative (also known as mixed ET), and congenital CN VI paralysis.

Associated deviations (in order of prevalence):

DVD or combined cyclovertical deviation: seen in 46 to 90% of cases, usually occurs at a later age, seen especially in abduction. Diagnose with remote cover test.

IOO: causes V-pattern ET, usually occurs after age 1, and is present in two thirds of patients by age 8.

Nystagmus: latent in 50% of cases, which is horizontal jerk when other eye is covered (to get VA, may need to fog with þ10 lens and not occlude the other eye). Rotary nystagmus present in 30% of cases; rarely may have manifest nystagmus.

Accommodative component: check cycloplegic refraction if the ET ‘‘recurs’’ after initial surgery.

Ciancia’s syndrome: extreme congenital ET with large angle, LN, restricted movements.

Treat refractive error first if present (usually not an issue), then treat amblyopia before surgery. Surgical goal is to align within 10 pD of ortho; usually wait until patient is 4 to 6 months old; usually perform bilateral MR recessions or LR resections (Table 9–6). Treat DVD/ IOO with anterior transpositions of SO (Harada-Ito procedure). Amblyopia management requires constant surveillance until patient is 7 to 8 years old.

Early intervention study: designed to find out if the angle is stable by 4 months. Previously, surgery was usually performed at 18 months.

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360 PEDIATRICS AND STRABISMUS

TABLE 9–6

Surgical Recession and Resection for Esotropia

Surgical goal is monofixation syndrome (horizontal deviation <10 pD, with a scotoma in the nonfixating eye under binocular conditions, with peripheral NRC). Only 39% of patients have stereopsis. No binocular vision if not surgically corrected by age 2 years.

ACCOMMODATIVE ESOTROPIA Cause of 70% of ET and 50% of all strabismus cases; characterized by acquired, comitant, moderate deviation (20–30 pD), with onset at 18 months to 7 years (average age 2.5 years; not surprising, as most neonates are not yet accommodating, and it often takes full accommodation to bring out the ET). Often intermittent and variable, then becomes constant; often hereditary and usually asymptomatic. Patients are either hyperopic or have high AC/A. May be precipitated by trauma, illness, accommodative targets with high spatial frequency, or fatigue at end of the day. Amblyopia is common due to a fixation preference or anisometropia; no motility restriction like acquired CN VI palsy. Have facultative suppression scotoma in the nasal retina (suppression only when eyes are deviated).

Four subtypes:

Nonrefractive (57%): high AC/A (>10 pD near vs. distant shows excessive convergence when patient accommodates); normal refraction. A higher AC/A ratio is predictive of deterioration of PET (Table 9–7).

Refractive (43%): hyperope (average þ 4.75 D) with normal AC/A and sensitive accommodation

Partially accommodative: part congenital ET

Decompensated accommodative ET: occurs from delay to spectacles or high AC/A

Treatment: amblyopia treatment and spectacles, then eventual surgery for residual ET.

Spectacles: give full cycloplegic prescription if patient is <6 years old, and give tolerated prescription if patient is >6 years old. Instruct parents to obtain glasses promptly and to use glasses full

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Based on data from Ludwig IH, Parks MM, Getson PR, Kammerman LA. Rate of deterioration in accommodative esotropia correlated to the AC/A relationship. J Pediatr Ophthalmol Strabismus 1988;25:8–12.

time; caution that patient may need to use bifocals and change prescription soon and that glasses are being used to improve alignment, not help the child to see better.

At follow-up, ask parents if ET is improved and if child is wearing glasses full time; check glasses with lensometer to ensure correct dispensing, and check glasses’ fit, patient stereopsis, and fusion and alignment in spectacles. Hold minus lenses in front of prescription; if patient holds fusion, may decrease plus prescription to wean off.

After visual maturity, can often wean down plus power.

High AC/A or if ET persists at near with full hyperopic correction. If patient is able to fuse at distance, consider

Bifocals: give þ3.00 bifocal (write for executive style or large flat-top segment if polycarbonate, which bisects pupil) to decrease near ET.

Miotics: parasympathomimetic, long-acting cholinesterase inhibitors facilitate acetylcholine transmission, and augment accommodative response and decrease AC/A ratio (vs. atropine, which increases the AC/A). Echothiophate iodide (PI) 0.125% every AM; at follow-up, look for miosis, ET controlled at distance and near after 3 to 4 weeks, then taper down. Many adverse drug reactions, including ciliary spasm with brow ache, blurred vision, cataract, iris cysts (prevent with concomitant phenylephrine drops), abdominal cramps, nausea, vomiting, diarrhea, salivation, and potentiates depolarizing agents; thus, patient should wear medical alert bracelet.

May consider bilateral medial rectus recession (BMRR) with or without Faden procedure.

Consider surgery if patient has residual >15 pD in glasses. Operate for distance angle plus 1 D or near deviation.

Prism Adaptation Study: a multicenter, randomized clinical trial (1984–1989) to determine whether preoperative use of prisms

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362 PEDIATRICS AND STRABISMUS

could improve surgical outcome for acquired esotropia. Patients with residual ET > 12 pD after full correction were treated with preoperative use of base-out (BO) Fresnel prism equal to the angle of ET. Responders, defined as simultaneous cover test deviation 0.8 pD or fusion on W4D, had 83% surgical success versus 72% for nonresponders ( p ¼ 0.04).

CYCLIC ESOTROPIA Comitant, intermittent ET every 48 hours that usually breaks down to constant ET; 1:4000 incidence.

DIVERGENCE INSUFFICIENCY ESOTROPIA ET > at distance; normal neurologic exam. Treat with BO prism.

DIVERGENCE PARALYSIS ESOTROPIA Similar to divergence insufficiency with no fusional vergences; need neurologic work-up to rule out pontine tumors, trauma.

DUANE’S RETRACTION SYNDROME (DRS) Accounts for 1% of all strabismus cases; characterized by horizontal gaze abnormalities (head turn), palpebral fissure narrowing from globe retraction, and upor downshoot on attempted adduction. Most are sporadic, but some may be familial; usually unilateral, but 20% are bilateral. From congenital agenesis of the abducens nucleus with the LR abnormally innervated by CN III that also supplies the MR. This aberrant innervation violates Sherrington’s law. More common in left eye and in females. Associated with cataract, iris abnormalities, Marcus Gunn jaw winking, microphthalmia, crocodile tears, Goldenhar’s syndrome, and Klippel-Feil syndrome. Treat amblyopia (present in 10–14% of cases), and consider surgery with MR Faden procedure to reduce the upshoot on adduction (fixate near the equator), or transpose SR and IR over toward the LR. Three types:

Type I: limitation of abduction (mnemonic: 1 ‘‘d’’ in abduction); most common type. Majority of patients are straight but may have esodeviation. Electromyogram shows no LR electrical activity on abduction with paradoxic activity with adduction.

Type II: limitation of adduction (mnemonic: 2 ‘‘d’’s in adduction); majority of patients are straight but may have exodeviation. Electromyogram shows LR active with both adduction and abduction.

Type III: limitation of abduction and adduction (mnemonic: 3 ‘‘d’’s in abduction and adduction); least common type. Electromyogram shows both LR and MR active with both adduction and abduction.

INCOMITANT ACQUIRED ESOTROPIA MR or LR restriction or dysfunction as seen with thyroid, postoperative, fracture, myasthenia gravis, and congenital CN VI palsy.

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