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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 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

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-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
  • Pachyonychia congenita syndrome OMIM #167200
    • onychogryposis
    • hyperkeratosis of the palms, soles, knees and elbows
    • tiny cutaneous horns in many areas
    • eukoplakia of the oral mucous membranes
    • Hyperhidrosis of the hands and feet

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 Pierpont ME, Brueckner M, Chung WK, et al. Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555769/. Circulation. 2018;138(21):e653-e711. doi:10.1161/CIR.0000000000000606.
Nance-Horan NHS Sometimes Yes Dental anomalies, facial features Pierpont ME, Brueckner M, Chung WK, et al. Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555769/. Circulation. 2018;138(21):e653-e711. doi:10.1161/CIR.0000000000000606., Rechsteiner D, Issler L, Koller S, et al. Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/10.1001/jamaophthalmol.2021.0385?utm_source=openevidence&utm_medium=referral. JAMA Ophthalmology. 2021;139(7):691-700. doi:10.1001/jamaophthalmol.2021.0385.
OFCD BCOR Yes (palate) Yes Cardiac, limb anomalies Rechsteiner D, Issler L, Koller S, et al. Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/10.1001/jamaophthalmol.2021.0385?utm_source=openevidence&utm_medium=referral. JAMA Ophthalmology. 2021;139(7):691-700. doi:10.1001/jamaophthalmol.2021.0385.
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. https://pubmed.ncbi.nlm.nih.gov/1219119. Journal of Medical Genetics. 1975;12(4):397-400. doi:10.1136/jmg.12.4.397.
Roberts ESCO2 Yes Yes Limb reduction, growth deficiency Pierpont ME, Brueckner M, Chung WK, et al. Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555769/. Circulation. 2018;138(21):e653-e711. doi:10.1161/CIR.0000000000000606.
Trisomy 13 Chromosomal Yes Yes Multiple anomalies Stoll C, Alembik Y, Roth MP. Co-Occurring Anomalies in Congenital Oral Clefts. https://pubmed.ncbi.nlm.nih.gov/35179301. American Journal of Medical Genetics. Part A. 2022;188(6):1700-1715. doi:10.1002/ajmg.a.62689.

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