Congenital cataract

An infant with lens opacity at or shortly after birth. Detected on the red-reflex check at the newborn or well-child exam (absent or asymmetric red reflex), or noted by parents as a "white spot" in the pupil. The clinical urgency is time-sensitive: a visually significant cataract present beyond about 6 to 8 weeks of life causes deprivation amblyopia, and that amblyopia is permanent. The systemic workup runs in parallel with the ophthalmologic intervention, not after it.

The single most useful organizing question is why the lens is cloudy:

1. Metabolic: an enzyme defect is depositing substrate in the lens. Often treatable; missing it costs more than the eye.
2. Infectious: congenital TORCH infection.
3. Syndromic: the cataract is one feature of a recognizable syndrome.
4. Isolated (familial): mendelian lens-specific gene defect, most often AD with an affected parent.

The second organizing question is unilateral vs bilateral. Bilateral cataracts skew strongly toward systemic causes (metabolic, syndromic, infectious, familial). Unilateral cataracts skew toward local ocular causes (persistent fetal vasculature, anterior segment dysgenesis, trauma) and rarely need a systemic workup, though one is still done.

Metabolic (treatable, must not miss)

• Classic galactosemia (GALT, AR): the medical emergency in this differential. Cataract appears within days to weeks of starting milk feeds; the infant also has jaundice, hepatomegaly, and is at high risk for E. coli sepsis. Switching to a soy formula is the immediate intervention while confirming with red-cell GALT activity. Newborn screening catches most cases but not all (and not on day of presentation).
• Lowe syndrome (oculocerebrorenal of Lowe) (OCRL, X-linked): bilateral congenital cataract plus intellectual disability plus renal Fanconi syndrome. The triad is the giveaway. Cataract is present at birth in essentially 100%.
• Smith-Lemli-Opitz syndrome (DHCR7, AR): cholesterol biosynthesis defect; cataract can be present along with 2-3 toe syndactyly, microcephaly, genital anomalies, growth failure.
• Peroxisomal disorders (Zellweger spectrum): rare, but cataract can be one feature in a profoundly hypotonic infant with hepatomegaly and seizures.
• Hypoparathyroidism / hypocalcemia: lens opacities can develop secondary to chronic hypocalcemia.

Infectious

• Congenital rubella: the classic triad is cataract + cardiac defect (PDA) + sensorineural deafness. Rare in countries with high vaccination coverage but still on the global differential.
• Other TORCH: less classic for cataract; toxoplasmosis and CMV cause chorioretinitis more often than lens opacity.

Syndromic

• Nance-Horan syndrome (NHS, X-linked): cataract plus dental anomalies (Hutchinson incisors, supernumerary teeth) plus mild dysmorphism. Female carriers often have posterior Y-sutural lens opacities.
• Hallermann-Streiff syndrome: bilateral microphthalmia and cataract, beaked nose, hypotrichosis, dental anomalies, proportionate short stature.
• Cockayne syndrome: cataract in the context of photosensitivity, progressive neurodegeneration, cachectic facies.
• Trisomy 21: congenital cataract is rare in Down syndrome (Brushfield spots are NOT cataracts); however, real cataracts are common in adults with Down syndrome.

Isolated familial (most often AD)

• Crystallins: CRYAA, CRYBB1, CRYBB2, CRYAB, CRYBA1. Each gives a characteristic morphology (lamellar, sutural, nuclear).
• Connexins: GJA8 (Cx50), GJA3 (Cx46). Often pulverulent or zonular opacities.
• MIP (major intrinsic protein / aquaporin 0): polymorphic congenital cataract.
• BFSP2, HSF4, PITX3: additional lens-development genes.

Examining both parents at the slit lamp is the first step in an AD familial cataract. The morphology in the parent often matches the proband.

1. Confirm and characterize the cataract. Pediatric ophthalmology slit-lamp: morphology (lamellar, sutural, nuclear, polar, pulverulent, total), laterality, visual significance.
2. Examine both parents at the slit lamp. A subtle inherited lens opacity in a healthy parent diagnoses isolated familial cataract before any lab is sent.
3. Galactosemia evaluation: newborn-screen result + confirmatory red-cell GALT enzyme activity; urine reducing substances (positive for galactose) is a quick bedside screen.
4. Electrolytes, glucose, urinalysis with amino acids: Lowe Fanconi tubulopathy is detectable on a basic metabolic panel plus urine studies.
5. TORCH titers if any features (deafness, cardiac, microcephaly) suggest congenital infection.
6. 7-dehydrocholesterol if Smith-Lemli-Opitz features are present.
7. Calcium, phosphate, PTH to rule out hypocalcemic cataract.
8. Chromosomal microarray + targeted gene panel (cataract or anterior-segment panel) when the picture is bilateral, isolated, and the parents are unaffected. Exome if panel is unrevealing.