Congenital Cataracts and Multiple Congenital Anomalies present
Congential Cataracts and Isolated Ocular Abnormalities
Congenital Cataracts and one organ system abnormality or one prominent feature
Congenital Cataracts without any other abnormality

Congenital Cataract- Stepwise approach to determining etiology

Preform History and Physical Examination to Determine if one of the following present

Multiple Congenital Anomalies
Isolated Ocular Abnormalities
One organ system abnormality
No other abnormalities

Congenital Cataracts and Multiple Congenital Anomalies present

Do Chromosome Analysis to screen for the following:

Trisomy 13
Trisomy 18
Trisomy 21
Turner Syndrome
Edward Syndrome
Partial Trisomy 10q
Translocations: 3:4, 2:14, 2:16

If Chromosome Analysis Normal consider:

Hallerman-Strieff syndrome: dental anomalies
Schprintzen syndrome: cardiac anomalies
Cerebral-oculo-facial syndrome: microcephaly
Cockayne syndrome: microcephaly
Fetal rubella syndrome: microcephaly
Marinesco-Sjögren syndrome: microcephaly
Mowat-Wilson syndrome
Rubenstein-Taybi syndrome: microcephaly
Smith-Lemli-Opitz syndrome: microcephaly
Walker-Warburg syndrome: hydrocephalus
Zellweger syndrome: long-chain fatty acids
Lowe Syndrome***

Congential Cataracts and Isolated Ocular Abnormalities

Aniridia
PHPV
Uveitis
Retinoblastoma

Congenital Cataracts and one organ system abnormality or one prominent feature

Short stature or limb abnormalities

Do skeletal survey to determine:

Short limbed dwarfism
- Camarati-Englemann syndrome
- Chondrodysplasia punctata
- Hypochondrodysplasia
- Kniest syndrome
Bony changes
- Fetal warfarin exposure
- Mannosidosis
- Marshall syndrome
- Stickler syndrome
- Schwartz-Jampel syndrome
Limb anomalities
- Fetal Varicella infection
- Klippel-Trenaunay-Weber syndrome
- Proteus syndrome
- Roberts syndrome

Muscle

Myotonic dystrophy: Muscle wasting

Aniridia and Wilms Tumor

Hearing disorder

Refsum disease
Alport syndrome

Dental abnormalities

May not be noted until teeth erupt

Canine radicomegaly
Nance-Horan syndrome (X-linked)
Oculo-dental digital syndrome

Skin abnormalities

Focal dermal hypoplasia
Gorlin syndrome
Incontinentia Pigmenti
Rothmund-Thompson syndrome
Fabry disease

Nail dystrophy

Clouston syndrome (hidrotic ectodermal dysplasia) OMIM #129500
- normal sweat and sebaceous gland function
- total alopecia
- severe dystrophy of the nails
- hyperpigmentation of the skin especially over the joints
- normal teeth
- strabismus
- mental deficiency
- clubbing of the fingers
- palmar hyperkeratosis
- extensive kindred of French extraction that migrated to Canada, Scotland, and northern United States
Nail-Patella syndrome OMIM #161200
- dysplasia of the nails
- absent or hypoplastic patellae (60-90%)
- abnormality of the elbows interfering with pronation and supination (60-90%)
- nephropathy
- hearing loss
- keratoconus
- glaucoma, microcornea, microphakia

Cleft Lip and Palate

Syndrome	Genetic Basis	Cleft Lip/Palate	Congenital Cataract	Other Features	References
Peter's Plus	B3GALTL	Yes	Yes	Short limbs, ID, heart defects	Liesbeth J.J.M. et al. The Peters’ plus syndrome: a review, Annales de Génétique 2002; 45(2):97-103
Nance-Horan	NHS	Sometimes	Yes	Dental anomalies, facial features	Rechsteiner D et al. Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract. JAMA Ophthalmology. 2021;139(7):691-700.
Oculofaciocardiodental syndrome (OFCD)	BCOR	Yes (palate)	Yes	Cardiac, limb anomalies	Rechsteiner D et al. Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract. JAMA Ophthalmology. 2021;139(7):691-700.
Stickler	COL2A1, COL11A1	Yes (palate)	Yes	Myopia, hearing loss, arthritis	Hall JG, Herrod H. The Stickler Syndrome Presenting as a Dominantly Inherited Cleft Palate and Blindness. 9. Journal of Medical Genetics. 1975;12(4):397-400.
Roberts	ESCO2	Yes	Yes	Limb reduction, growth deficiency	Pierpont ME, et al. Genetic Basis for Congenital Heart Disease. Circulation. 2018;138(21):e653-e711.
Trisomy 13	Chromosomal	Yes	Yes	Multiple anomalies	Stoll C,et al. Co-Occurring Anomalies in Congenital Oral Clefts. American Journal of Medical Genetics. Part A. 2022;188(6):1700-1715.

Congenital Cataracts without any other abnormality

Do a screen for the following:

CBC: elevated white count
Blood Glucose or HbA1C: hyperglycemia
RBC Galactokinase serum level: galactosemia
TORCH titer
- IgG (maternal may last 6 months) and consider IgM if signs of inflammation
- Toxoplasma- IgG +/- IgM
- Syphilis- total antibodies with reflex confirmation
- Rubella- IgG +/- IgM
- Cytomegalovirus IgG +/- IgM
- Herpes- HSV 1&2 specific IgG +/- IgM

If screen above is normal: Early onset Cataract genetic testing program by Travere Therapeutics (18 months to 35 years old with infection causes ruled out): LINK

Consider Genetics referral if syndrome above suspected

cataract

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