Syndromes Flashcards
Weill-Marchesani syndrome (WMS)
opposite of Marfan’s
Child with: high myopia, brachydactyly, and relatively short stature. Microspherophakia (may result in pupillary block glaucoma with markedly-high IOPs; therefore prophylactic PI)
no formal criteria for the Dx.
ectopia lentis, joint stiffness, heart defects, and a broad head (brachycephaly).
Mutations:
ADAMTS10 encodes a zinc-dependent protease.
FBN1 (encoding fibrillin-1)
Cycloplegic during the actual attack of pupillary block glaucoma since it would allow the small lens to move back posteriorly.
Mnemonic: ADAM Weil FIBs online about his broad head and shortness. He is Myopic and microspherophakic. He tries to find love online because he has heart problems and joint stiffness.
Brown syndrome
Both inferior rectus restriction and Brown syndrome will present with DEFICIENT ELEVATION on ADDUCTION (although more so for Brown syndrome). To accentuate the restriction in Brown syndrome, elevation inadduction can be tested during retropulsion.
Retropulsion stretches the SUPERIOR OBLIQUE TENDONand therefore, the restriction would be increased if it is due to Brown syndrome.
In contrast for inferior rectus restriction, the restriction would be increased during forceps-inducedproptosis(i.e. not retropulsion).
As adduction is increased, there is typically anabrupt downshoot in Brown syndrome. In superior oblique overaction, the downshoot is less abrupt.
De Morsier syndrome
De Morsier syndrome, or septo-optic dysplasia (SOD), is a congenital disease marked by midline brain developmental abnormalities and unilateral or bilateral optic nerve hypoplasia. Vision can range from near normal to severely impaired. Nystagmus is frequently present and develops around age 1-4 months when the pathways required for normal fixation typically mature. In children with SOD, the diagnosis is not typically a mystery because the fundus exam will show optic nerve hypoplasia
The most common pituitary hormone deficiency that occurs in this syndrome is GROWTH HORMONE DEFICIENCY. However, decreased secretion of the other pituitary hormones can occur as well (e.g. ACTH, ADH, TSH, LH, FSH).
There is more recent thinking that the term, “de Morsier syndrome,” should be abandoned since: hypopituitarism can occur in ONH patients independent of the presence or absence of the septum pellucidum.
Oil droplet cataracts
Oil droplet cataracts are classically found in patients with galactosemia. This cataract presents as a faint irregularity in the central aspect of the posterior lens cortex and is best seen on retroillumination.
Cerulean (“blue-dot”) cataracts
Cerulean (“blue-dot”) cataracts are bilateral, small, bluish-white opacities in the peripheral cortex. They are typically asymptomatic and can be associated with Down’s syndrome, but can also be found in normal individuals during puberty.
Anterior subcapsular cataracts
Anterior subcapsular cataracts are associated with trauma
Mobius syndrome
Mobius syndrome is a very rare disorder defined by cranial nerve VI and VII palsies. The facial nerve palsy results in a characteristic “masked facies”. In addition, individuals with Mobius syndrome may have limb abnormalities (e.g. clubbed feet), chest-wall defects, and a deformed tongue among other abnormalities. They can also have impaired adduction, as in this case, which is somewhat improved on convergence.
Lowe syndrome
Lowe syndrome which is also known as “oculocerebrorenal syndrome”: glaucoma, cataracts, renal tubular dysfunction, MR.
Lowe syndrome is a very rare, X-linked disease with an estimated prevalence of 1 to 10 affected males in 1 million people. It is caused by a reduction of phosphatidylinositol (4,5) bisphosphate 5 phosphatase activity below 10% in fibroblasts.
The ocular findings in Lowe syndrome are dense cataracts in all patients (disciform [membranous] cataracts), glaucoma in 50% of patients (usually developing during the 1st year of life), and corneal and conjunctival keloids (25% of patients).
Typically, severe hypotonia is present at birth which may compromise suction and result in severe respiratory problems during early life. Approximately 10% will have mild mental retardation while the majority (>75%) will display overaggressive behavior.
The kidney problems in Lowe syndrome is due to renal Fanconi syndrome which results in renal tubular acidosis, proteinuria, phosphate wasting, hypercalciuria, aminoaciduria, and hypokalemia. These renal abnormalities result in failure to thrive and rickets.
Crouzon syndrome
MC craniosynostosis
AD - assoc/w/30+ mutations of FGFR2 on chr10.
Shallow orbits, proptosis
Midface hypoplasia
Normal intelligence
Risk of elevated ICP
fusion of both coronal sutures= “tower skull”.
V-pattern exotropia =MC strabismus pattern in craniosynostosis syndromes. This pattern is often accompanied by significant inferior oblique overaction.
Seathre-Chotzen syndrome
Seathre-Chotzen syndrome is a much milder craniosynostosis . It is often under-diagnosed, due to the mild features of the syndrome. Intelligence is usually normal and only occasionally do these patients display slightly short digits of their hands
Since the skull deformity in Saethre-Chotzen syndrome is quite mild, this syndrome often goes undiagnosed. It typically consists of plagiocephaly, ptosis, mild brachydactyly, and mild syndactyly. There is a characteristic lateral deviation of the big toes of the feet. This mild craniosynostosis syndrome is caused by mutations in the TWIST gene on chromosome 7.
Apert syndrome
Basically: Crouzon with syndactyly
Oftentimes, Apert’s syndrome patients have completely fused hands and feet.
most have: one of two specific mutations of the FGFR2
Pierre Robin
Cleft palate
Small mandible
Glossoptosis
Common in what syndrome?
Stickler syndrome
Pierre Robin sequence, is technically not a craniosynostosis and also not associated with syndactyly.
Aniridia
The actual name of this disease is a misnomer since there is always some iris remnant present.
The main ocular conditions that occur in aniridia are:
chronic angle closure glaucoma progressive corneal opacification nystagmus foveal hypoplasia cataracts
The corneal opacification occurs due to limbal stem cell deficiency. Therefore, limbal stem cell transplantation is indicated if this opacification occurs (then followed by a corneal transplant). Alternatively, a keratoprosthesis can be considered for aniridic patients with significant corneal opacity.
As stated ad nauseum elsewhere on this website, SPORADIC cases of aniridia are much more commonly associated with Wilms tumor. For these patients, a renal ultrasound is mandatory to exclude this life-threatening tumor.
PSC cataracts
NF2
neurofibromatosis type 2 whose classic findings are bilateral acoustic neuromas, cafe-au-lait spots (60%), combined retinal-RPE hamartomas, and posterior subcapsular cataracts.
The clinical vignette is alluding to a diagnosis of neurofibromatosis type 2 (NF-2) which is one of the commonly-tested phakomatoses. NF-2 is an autosomal dominant genetic syndrome that is caused by mutations in the NF2 gene which is located on chromosome 22. This gene produces the protein merlin (aka schwannomin) which acts as a tumor suppressor gene.
This syndrome predisposes individuals to multiple tumors of the nervous system including bilateral vestibular schwannomas (resulting in hearing loss and tinnitus), intracranial and spinal meningiomas, and schwannomas of other cranial nerves.
The most common ocular pathology found in individuals affected by NF2 are cataracts (60-80% are affected). The most common type of cataract is the posterior subcapsular variety. The BCSC also states that wedge cortical cataracts are commonly found in these patients.
Less common ocular findings in NF2 are retinal hamartomas, combined hamartomas of the retina and RPE, optic nerve meningiomas, and epiretinal membranes.
Delayed Visual Maturation
Sometimes, when the results of an eye exam are completely normal in a baby, but the baby does not fixate and follow or has poor fixation, the patient may have delayed visual maturation (DVM). Although, DVM is more commonly seen in babies with other developmental disabilities and in children with neurological impairment, it can also be seen in otherwise healthy babies. Close observation to see if vision develops is appropriate.
As the baby approaches 12 months of age, a visual evoked cortical potential is appropriate. Observation is acceptable if
Midface hypoplasia
Premature fusion of the skull base suture produces only one kind of abnormality called “midface hypoplasia”.
Abnormal fusion of the calvarial sutures (e.g. coronal, sagittal, etc) can produce a variety of skull malformations (e.g. plagiocephaly, scaphocephaly, etc).
dorsal midbrain syndrome
The classic signs of dorsal midbrain syndrome (aka “Parinaud syndrome”) are:
paralysis of upgaze
defective (voluntary) convergence
pupillary light-near dissociation
convergence-retraction "nystagmus"
eyelid retraction ("Collier's sign")
The convergence-retraction “nystagmus” is not considered a true nystagmus but rather a disjunctive saccadic oscillation. To elicit this movement, the patient is asked to track a downward-rotating OKN drum which will elicit an attempted upward saccade. Instead of a normal upward saccade, the patient with this syndrome will exhibit convergence and retraction of both eyes since there is co-contraction of all horizontal extraocular muscles (the medial recti acting more forcefully than the lateral recti). However, voluntary convergence movements are minimal.
Typically, upward saccades are initially affected but upward pursuit movements can become affected as well. Eventually, even vestibulo-ocular responses (i.e. Dolls’ head responses) and Bell’s phenomenon can be paralyzed.
In children, the most common causes of dorsal midbrain syndrome are pinealoma and congenital aqueductal stenosis. In young adult women, it is typically caused by multiple sclerosis. In elderly patients, the most common cause is midbrain stroke.
Aicardi syndrome
Oval chorioretinal lacunae = the classic finding of Aicardi Syndrome. X-linked dominant condition (i.e. lethal in males, except if person is XXY [Klinefelter] ), although the gene that causes this syndrome has not been identified as of 2012.
The classic triad of Aicardi syndrome is chorioretinal lacunae, agenesis of the corpus callosum, and infantile spasms. Other ocular abnormalities include colobomas and microphthalmos. Infantile spasms typically develop before the age of 5 months and these individuals experience significant developmental delay.
Ectopia lentis et pupillae
Ectopia lentis et pupillae is an asymmetric, bilateral condition in which the lens subluxation is in the opposite direction of the eccentric pupils. Therefore in this example, the lenses would be subluxed inferonasally.
This condition is often said to be inherited in an autosomal recessive fashion, though there is some evidence that it can also be inherited in an autosomal dominant with reduced penetrance pattern. Other associated ocular findings include: poor pupillary dilation, persistent pupillary membrane, iris transillumination defects, early cataract, glaucoma, high myopia, and retinal detachment.
Batten syndrome
Batten’s disease which can result in optic atrophy, macular pigmentary deposits, and low/absent ERG. Patients with the different types of neuronal ceroid lipofuscinosis (Batten disease) can present with seizures, but typically a little later in life.
Blepharophimosis
The external photo demonstrates the 4 classic ocular features of the blepharophimosis syndrome which are:
Blepharophimosis – narrowed horizontal palpebral aperture
Ptosis – due to poor levator function from dysplasia of the levator aponeurosis
Telecanthus – normal interpupillary distance but wide intercanthal distance
Epicanthus inversus –prominent fold of skin arising from the lower eyelid and covering the medial canthus
This autosomal dominant disorder is also called the “blepharophimosis-ptosis-epicanthus inversus” (BPES) syndrome and is categorized into 2 types. It is caused by a mutation in the FOXL2 gene on chromosome 3.
BPES type 1 is characterized by the above ocular features as well as premature ovarian failure leading to infertility. There is complete penetrance and transmission occurs via males (due to reduced fertility in females) for this subgroup of BPES.
BPES type 2 features the ocular features, but does not have the premature ovarian failure. There is incomplete penetrance and it is transmitted by both sexes equally.
Other ophthalmic findings in BPES include: strabismus, amblyopia (either from the ptosis or strabismus), possible microphthalmos, and tear duct abnormalities.
Other systemic findings in BPES include: flat nasal bridge, arched palate, and cup-shaped (“lop”) ears.
Management of the eyelid abnormalities is beyond the scope of this answer explanation, but typically the epicanthus inversus and telecanthus are corrected before ptosis repair. This sequence of surgeries is due to the fact that medial canthus reconstruction often worsens the ptosis.
However, the BCSC actually states that repair of the epicanthus and telecanthus is often delayed since they may improve with age. Also, the BCSC states that ptosis repair with frontalis suspension is often needed early in life.
Kawasaki
The external photographs show the characteristic fissured lips and bilateral conjunctival injection which are characteristic findings of “Kawasaki disease”. Another characteristic finding (not shown in the photo) is inflamed tongue papillae (i.e. “strawberry tongue”).
This is a systemic vasculitis affecting medium-sized vessels and affects many organ systems, most importantly the coronary arteries. Because of the risk of death from coronary artery aneurysms, a 2-dimensional echocardiogram should be obtained. An anterior uveitis can occur in this disease, but it usually is self-limited and does not require treatment. Systemic treatment of Kawasaki disease is with aspirin. Systemic corticosteroids should never be given due to the risk of worsening the rate of coronary artery aneurysm formation.
Aniridia
Aniridia is a disease marked by bilateral hypoplastic irides, foveal hypoplasia with poor visual acuity, and frequent nystagmus. Other associated common features include glaucoma, optic nerve hypoplasia, cataracts, and the development of diffuse corneal scarring later in life from limbal stem cell deficiency.
The disease is caused by PAX6 gene mutations and can be hereditary or arise de novo. In those cases of hereditary aniridia there is no increased risk for Wilms tumor (also known as nephroblastoma) over the general population. In patients with seemingly sporadic aniridia, up to one third of patients will develop Wilms tumor and most are diagnosed with the tumor by 5 years of age. All children with sporadic aniridia should undergo genetic testing for the Wilms tumor genetic defect.
Most patients with aniridia will have photosensitivity simply due to the large amount of light entering the eye. Myelinated nerve fiber layer is associated with refractive amblyopia but is not commonly associated with aniridia.
Christmas tree cataracts
The slit-lamp photo shows the classic appearance of a “Christmas tree cataract” (i.e. “multicolor flecks”). The two conditions that this type of lens opacity can be associated with are: myotonic dystrophy and hypoparathyroidism.
The symptoms of hypoparathyroidism are related to the low serum calcium levels that this condition induces. Therefore, these patients commonly experience paresthesias in their extremities and perioral region as well as the phenomenon of tetany. This latter sign can be elicted via tapping on the root of the facial nerve to induce tetany of the facial muscles (i.e. Chvostek’s sign). These patients typically have normal intelligence.
Patients with myotonic dystrophy can exhibit “myotonia” or inability to relax muscles when stimulated. The typical clinical vignette illustrating this is a patient who cannot release their handshake quickly. In contrast to patients with hypoparathyroidism, these patients typically display low intelligence. Other features of myotonic dystrophy are ptosis, CPEO (chronic progressive external ophthalmoplegia), pigmentary retinopathy, and cardiac conduction abnormalities. Also assoc/w/HYPOtension.
The typical cataract associated with Lowe’s syndrome is the “thin disciform” cataract.
Patients with myotonic dystrophy type I (DMI) are known to have low intraocular pressures and it is hypothesized to be secondary to ciliary body detachments (please see http://www.ncbi.nlm.nih.gov/pubmed/20801513).
ectropion uveae
ectropion uveae is actually a misnomer since the iris posterior epithelium is not considered part of the uvea. An alternative name is iris ectropion. This abnormality can occur either as an acquired tractional abnormality (e.g. from neovascularization of the iris) or can be congenital in origin (i.e. congenital iris ectropion).
The constellation of unilateral congenital iris ectropion, high iris insertion, smooth (cryptless) iris surface, and glaucoma is called congenital iris ectropion syndrome. This syndrome may be associated with systemic syndromes like neurofibromatosis (NF), primary facial hemihypertrophy, Rieger anomaly, and Prader- Willi syndrome. Café au lait spots are common cutaneous manifestations of NF.
Myelinated nerve fiber layer
Basal Cell Nevus Syndrome (Gorlin-Goltz Syndrome) is an uncommon autosomal dominant, multi-systemic disorder characterized by multiple basal cell carcinomas, skeletal abnormalities, odontogenic keratocyst, and intracranial calcification.
Myelinated nerve fiber layer is common with this disorder. Myelinated nerve fiber layers can be associated with neurofibromatosis 1, ipsilateral high myopia, strabismus, and amblyopia.
Alstrom syndrome
Dilated cardiomyopathy is one of the systemic manifestations of Alström syndrome. This very rare genetic disorder features a cone-rod dystrophy leading to early blindness as its ocular manifestation.
Alström syndromeis an autosomal recessive disorder chararacterized by a tapetoretinal degeneration, obesity, diabetes, hearing loss, renal failure, and dilatedcardiomyopathy. Unlike the other pigmentary retinopathies,central vision is lost early in Alström syndrome. Unlike BBS, there is no polydactyly, hypogonadism, or mental retardation in these patients.
Basal Cell Nevus Syndrome
Basal Cell Nevus Syndrome (Gorlin-Goltz Syndrome) is an uncommon autosomal dominant, multi-systemic disorder characterized by multiple basal cell carcinomas, skeletal abnormalities, odontogenic keratocyst, and intracranial calcification. Also myelinated nerve fiber layer
