autosomal recessive

Brittle Cornea Syndrome 2

Clinical Characteristics

Ocular Features

Corneal thinning and extreme fragility are characteristic of BCS2.  Ruptures of the cornea may occur with minimal trauma and repair is often unsatisfactory due to the lack of healthy tissue.  Keratoconus, acute hydrops, keratoglobus, and high myopia are frequently present as well.  Some patients have sclerocornea that obscures the normal limbal landmarks.  The sclera is also thin and the underlying uveal tissue imparts a bluish discoloration to the globe which is especially evident in the area overlying the ciliary body creating what some call a blue halo.

Systemic Features

Skin laxity with easy bruisability, pectus excavatum, scoliosis, congenital hip dislocation, a high arched palate, mitral valve prolapse and recurrent shoulder dislocations are often present.  Hearing impairment with mixed sensorineural/conductive defects is common.

Genetics

This autosomal recessive disorder results from homozygous mutations in PRDM5 (4q27).  Heterozygous carriers may have blue sclerae, small joint hypermobility, and mild thinning of the central cornea. 

BCS2 has many clinical similarities to brittle cornea syndrome 1 (229200) which results from homozygous mutations in ZNF469.

Treatment Options

Treatment for specific defects such as joint dislocations and mitral valve malfunction may be helpful.

References

Burkitt Wright EM, Porter LF, Spencer HL, Clayton-Smith J, Au L, Munier FL, Smithson S, Suri M, Rohrbach M, Manson FD, Black GC. Brittle cornea syndrome: recognition, molecular diagnosis and management. Orphanet J Rare Dis. 2013 May 4;8(1):68. [Epub ahead of print]

PubMed ID: 
23642083

Burkitt Wright EM, Spencer HL, Daly SB, Manson FD, Zeef LA, Urquhart J, Zoppi N, Bonshek R, Tosounidis I, Mohan M, Madden C, Dodds A, Chandler KE, Banka S, Au L, Clayton-Smith J, Khan N, Biesecker LG, Wilson M, Rohrbach M, Colombi M, Giunta C, Black GC. Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance. Am J Hum Genet. 2011 Jun 10;88(6):767-77. Erratum in: Am J Hum Genet. 2011 Aug 12;89(2):346.

PubMed ID: 
21664999

Aldahmesh MA, Mohamed JY, Alkuraya FS. A novel mutation in PRDM5 in brittle cornea syndrome. Clin Genet. 2011 Nov 29. doi: 10.1111/j.1399-0004.2011.01808.x. [Epub ahead of print]

PubMed ID: 
22122778

Chorioretinopathy with Microcephaly 1

Clinical Characteristics

Ocular Features

The ocular features have not been well described.  Small corneas, hyperopia, pale optic nerves and a variety of pigmentary changes in the retina have been reported.  The latter may consist of diffuse, fine or granular pigmentary changes.  Areas of pigmentary atrophy are often associated with patchy areas of pigmentary clumping.  These changes are usually located posterior to the equator.  Choroidal vessels may be sparse where the RPE is absent.  It has been suggested that the patchy pattern of retinal pigmentation resembles ocular toxoplasmosis.  Strabismus is common.  One report suggests microphthalmos in a patient.  Vision has been reported as subnormal from the first year of life but no quantitative data are available.

Systemic Features

Microcephaly is a consistent feature.  The forehead is steeply sloped but facial size appears normal.  The palate is highly arched.  Patients often have hyperactive deep tendon reflexes and walk with a shuffling gait.  Children are often hyperactive and highly social.  Intelligence quotients are usually subnormal. No lymphedema has been reported.  At least some patients have cutis marmorata.

On MRI diffuse pachygryria is seen.  The vermis is hypoplastic and the surface area of the corpus callosum is reduced to half of normal. 

Genetics

Parental consanguinity was present in two reported families and pedigrees suggest autosomal recessive inheritance with homozygosity of TUBGCP6 (22p22) responsible.

This presumed recessive disorder appears to be different than the autosomal dominant disorder of lymphedema, microcephaly, and chorioretinal dysplasia  (MCLMR(152950) although molecular confirmation is lacking.

For somewhat similar disorder see Chorioretinopathy with Microcephaly 2 (616171) and Chorioretinopathy with Microcephaly 1.

Treatment Options

Treatment is supportive.

References

Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA, Achilly NP, Cassidy RP, Fiorentini CJ, Heiken KF, Lawrence JJ, Mahoney MH, Miller CJ, Nair DT, Politi KA, Worcester KN, Setton RA, Dipiazza R, Sherman EA, Eastman JT, Francklyn C, Robey-Bond S, Rider NL, Gabriel S, Morton DH, Strauss KA. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One. 2012;7(1):e28936. Epub 2012 Jan 17. PubMed PMID: 22279524.

PubMed ID: 
22279524

Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA, Achilly NP, Cassidy RP, Fiorentini CJ, Heiken KF, Lawrence JJ, Mahoney MH, Miller CJ, Nair DT, Politi KA, Worcester KN, Setton RA, Dipiazza R, Sherman EA, Eastman JT, Francklyn C, Robey-Bond S, Rider NL, Gabriel S, Morton DH, Strauss KA. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One. 2012;7(1):e28936. Epub 2012 Jan 17. PubMed PMID: 22279524.

PubMed ID: 
22279524

Cant?? JM, Rojas JA, Garc??a-Cruz D, Hern?degndez A, Pag?degn P, Fragoso R, Manzano C. Autosomal recessive microcephaly associated with chorioretinopathy. Hum Genet. 1977 Apr 15;36(2):243-7.

PubMed ID: 
870417

McKusick VA, Stauffer M, Knox DL, Clark DB. Chorioretinopathy with hereditary microcephaly. Arch Ophthalmol. 1966 May;75(5):597-600.

PubMed ID: 
5936364

Ectopia lentis, Isolated AR

Clinical Characteristics

Ocular Features

Most dislocated lenses of non-traumatic origin are associated with syndromes, particularly those with defective connective tissue.  However, a few families with dislocated lenses have been reported in which no evidence of defective collagen is present.  The lens is most commonly displaced temporally, often creating myopic astigmatism.  The mean age of discovery of the dislocated lenses is about 2 years of age.  The eye is otherwise normally formed, intraocular pressure is normal, and the axial length is in the normal range.  The cornea, pupil, and iris are normal unlike that found in many patients with ectopia lentis et pupillae (225200).

Systemic Features

None by definition.

Genetics

Homozygous nonsense mutations in ADAMTSL4 (1q21.3) are responsible for this autosomal recessive condition.  The same gene is mutated in ectopia lentis et pupillae (225200).  A patient has been reported with craniosynostosis and ectopia lentis in which there was a homozygous 20 bp deletion in this gene.

An autosomal dominant condition of isolated dislocated lenses (129600) secondary to a mutation in FBN1 has also been reported.

Treatment Options

Lens removal may be indicated when vision cannot otherwise be corrected.

References

Chandra A, Aragon-Martin JA, Sharif S, Parulekar M, Child A, Arno G. Craniosynostosis with Ectopia Lentis and a Homozygous 20-base Deletion in ADAMTSL4. Ophthalmic Genet. 2012 Aug 7. [Epub ahead of print].

PubMed ID: 
22871183

Ahram D, Sato TS, Kohilan A, Tayeh M, Chen S, Leal S, Al-Salem M, El-Shanti H. A homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis. Am J Hum Genet. 2009 Feb;84(2):274-8.

PubMed ID: 
19200529

al-Salem M. Autosomal recessive ectopia lentis in two Arab family pedigrees. Ophthalmic Paediatr Genet. 1990 Jun;11(2):123-7.

PubMed ID: 
2377351

Microphthalmia with Limb Anomalies

Clinical Characteristics

Ocular Features

Patients have either microphthalmia or anophthalmia which may be present unilaterally or bilaterally.  The MRI in several patients has revealed complete absence of the globes, optic nerves, chiasm, and optic tracts.  The eyelashes are often sparse with shortened palpebral fissures and broad lateral eyebrows.

Systemic Features

Global developmental delays, failure to thrive, and mild to moderate mental retardation are common.   Syndactyly, polydactyly, and oligodactyly with hypoplasia of the long bones are present to a variable degree.  Synostosis in the digits, ankles, and wrist is often seen.  A split hand (lobster-claw deformity) is variably present.  Other anomalies such as the kidneys (horseshoe kidney), undescended testes, anomalous venous circulation and deformed vertebrae have been reported.  The midface is often flattened.  A high palate, cleft lip, and mild scoliosis may be seen.

Genetics

This is an autosomal recessive disorder resulting from homozygous mutations in the SMOC1 gene (14q24.2) but there is some evidence of genetic heterogeneity as the disorder has been mapped to 10p11.23 in several families.  However, no causative mutations were found in this region.  Consanguinity among parents is common.

Treatment Options

There is no treatment in most cases for the ocular malformations.  Some of the limb anomalies may be surgically correctable.

References

Abouzeid H, Boisset G, Favez T, Youssef M, Marzouk I, Shakankiry N, Bayoumi N, Descombes P, Agosti C, Munier FL, Schorderet DF. Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1, cause waardenburg anophthalmia syndrome. Am J Hum Genet. 2011 Jan 7;88(1):92-8.

PubMed ID: 
21194680

Okada I, Hamanoue H, Terada K, Tohma T, Megarbane A, Chouery E, Abou-Ghoch J, Jalkh N, Cogulu O, Ozkinay F, Horie K, Takeda J, Furuichi T, Ikegawa S, Nishiyama K, Miyatake S, Nishimura A, Mizuguchi T, Niikawa N, Hirahara F, Kaname T, Yoshiura K, Tsurusaki Y, Doi H, Miyake N, Furukawa T, Matsumoto N, Saitsu H. SMOC1 is essential for ocular and limb development in humans and mice. Am J Hum Genet. 2011 Jan 7;88(1):30-41.

PubMed ID: 
21194678

Hamanoue H, Megarbane A, Tohma T, Nishimura A, Mizuguchi T, Saitsu H, Sakai H, Miura S, Toda T, Miyake N, Niikawa N, Yoshiura K, Hirahara F, Matsumoto N. A locus for ophthalmo-acromelic syndrome mapped to 10p11.23. Am J Med Genet A. 2009 Mar;149A(3):336-42.

PubMed ID: 
19208380

Aphakia, Congenital Primary

Clinical Characteristics

Ocular Features

There is complete absence of the lens and with it aplasia of the anterior segment including complete absence of the iris, ciliary body, and trabecular meshwork.  In an autopsied case, the cornea was thinned and lacked endothelium, Bowman layer, and Descemet membrane while the retina was dysplastic.  In the single family reported, 2 sibs had sclerocornea and one had megalocornea.  Normal pressure was reported in several eyes but a single eye in one patient at the age of 3 years developed buphthalmos with elevated pressure.

Systemic Features

No systemic abnormalities have been reported.

Genetics

Homozygosity of a nonsense mutation in the FOXE3 gene (1p32) seems to be responsible for this autosomal recessive disorder.  The same gene has been implicated in rare cases of Peters anomaly (604229) and in anterior segment mesenchymal dysgenesis (107250).

Treatment Options

No treatment is known to restore vision.

References

Valleix S, Niel F, Nedelec B, Algros MP, Schwartz C, Delbosc B, Delpech M, Kantelip B. Homozygous nonsense mutation in the FOXE3 gene as a cause of congenital primary aphakia in humans. Am J Hum Genet. 2006 Aug;79(2):358-64.

PubMed ID: 
16826526

Johnson BL, Cheng KP. Congenital aphakia: a clinicopathologic report of three cases. J Pediatr Ophthalmol Strabismus. 1997 Jan-Feb;34(1):35-9.

PubMed ID: 
9027678

Microphthalmia, Syndromic 9

Clinical Characteristics

Ocular Features

Both microphthalmia and clinical anophthalmia have been described in this syndrome.  However, autopsy has shown true anophthalmia in a few cases who were stillborn or died in the neonatal period.  At least one eye can be cystic. The optic nerves are often hypoplastic and may be absent.  High, upward-arching eyebrows may be seen.

Systemic Features

An early manifestation of this disorder is neonatal pulmonary distress.  The lungs are usually hypoplastic or malformed. Cardiac malformations such as patent ductus arteriosus, septal and valvular defects, tetralogy of Fallot, and single ventricles are often present.  Diaphragmatic hernias or defects are common but hiatal hernias and frank eventration of abdominal contents have also been reported.  Renal anomalies and intrauterine growth retardation have been noted.         

Some infants have micrognathia, low-set ears, a broad nasal bridge, brachycephaly, and midline clefts of the palate.  Cerebral malformations are seldom present.

Genetics

Homozygous mutations in the STRA6 gene (15q24.1) have been found in a few cases which suggests autosomal recessive inheritance.  Parental consanguinity has been reported in some families.

Treatment Options

Treatment is directed at the repair of the organ defects in selected cases that have survival potential.   Survival rates are poor but those less severely affected may live for a decade.

References

West B, Bove KE, Slavotinek AM. Two novel STRA6 mutations in a patient with anophthalmia and diaphragmatic eventration (Letter). Am J Med Genet A. 2009 Mar;149A(3):539-42.

PubMed ID: 
19213032

Chitayat D, Sroka H, Keating S, Colby RS, Ryan G, Toi A, Blaser S, Viero S, Devisme L, Boute-B?(c)n?(c)jean O, Manouvrier-Hanu S, Mortier G, Loeys B, Rauch A, Bitoun P. The PDAC syndrome (pulmonary hypoplasia/agenesis, diaphragmatic hernia/eventration, anophthalmia/microphthalmia, and cardiac defect) (Spear syndrome, Matthew-Wood syndrome): report of eight cases including a living child and further evidence for autosomal recessive inheritance. Am J Med Genet A. 2007 Jun 15;143A(12):1268-81.

PubMed ID: 
17506106

Pasutto F, Sticht H, Hammersen G, Gillessen-Kaesbach G, Fitzpatrick DR, N?ornberg G, Brasch F, Schirmer-Zimmermann H, Tolmie JL, Chitayat D, Houge G, Fern?degndez-Mart??nez L, Keating S, Mortier G, Hennekam RC, von der Wense A, Slavotinek A, Meinecke P, Bitoun P, Becker C, N?ornberg P, Reis A, Rauch A. Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation. Am J Hum Genet. 2007 Mar;80(3):550-60.

PubMed ID: 
17273977

Iridogoniodysgenesis and Skeletal Anomalies

Clinical Characteristics

Ocular Features

Megalocornea, congenital glaucoma, a concave iris with stromal atrophy and corectopia, and deep anterior chambers are typical ocular features.  High myopia has been reported and retinal detachments have been observed.  Glaucoma control can be difficult to achieve and there is a significant risk of cataracts and phthisis bulbi following surgery.  Posterior embryotoxon has not been observed.

Systemic Features

Facial features seem to be consistent.  The forehead is wide, the nose appears broad with a large nasal tip and broad nares although the bridge appears narrow.  The philtrum is long and wide.  The ears may appear large and the neck is short.  The thorax is abnormally wide and the nipples are widely spaced and umbilicated.  The long bones are slender with thin cortices and wide metaphyses.  There is generalized osteopenia.  Vertebral bodies are cuboid-shaped with narrow vertebral canals and enlarged apophyses

Genetics

Two non-consanguineous families each with 3 sibs have been reported suggesting autosomal recessive inheritance.  Nothing is known about the mutation or its locus.

The ocular features may resemble Rieger or Axenfeld anomaly but these are inherited in autosomal dominant patterns and the skeletal features are dissimilar.       

Treatment Options

Vigorous treatment of glaucoma is indicated but successful control, even with surgery, is difficult to achieve.

References

Rodr??guez-Rojas LX, Garc??a-Cruz D, Mendoza-Topete R, Barba LB, Barrios MT, Pati?+-o-Garc??a B, L??pez-Cardona MG, Nu?+-o-Arana I, Garc??a-Ortiz JE, Cant?? JM. Familial iridogoniodysgenesis and skeletal anomalies: a probable new autosomal recessive disorder. Clin Genet. 2004 Jul;66(1):23-9.

PubMed ID: 
15200504

Garc??a-Cruz D, Mendoza R, Villar V, Sanchez-Corona J, Garc??a-Cruz MO, Rojas Q, Chavez-Anaya F, Nazara Z, Barrios MT, Cantu JM. A distinct dysmorphic syndrome with congenital glaucoma and probable autosomal recessive inheritance. Ophthalmic Paediatr Genet. 1990 Mar;11(1):35-40.

PubMed ID: 
2348980

Stickler Syndrome, Type IV

Clinical Characteristics

Ocular Features

Evidence of vitreoretinal degeneration is common and the risk of retinal detachment is high.  High myopia is common.  Cataracts are not a feature in contrast to types I and II Stickler syndrome.

It is likely that the ocular phenotype will be expanded with the report of additional families.

Systemic Features

Sensorineural hearing loss and short stature are often present. The latter is not usually a feature in other types of Stickler syndrome.  However, midface hypoplasia and micrognathia may be present in all types as well as in Marshall syndrome.  Midline clefting usually does not occur.

Genetics

A reported pedigree suggests autosomal recessive inheritance based on parental consanguinity and the lack of parent-to-child transmission.  Affected individuals have homozygous deletion mutations leading to loss of function in COL9A2 (1p33-p32) while parents are heterozygous.  A family with mutations in COL9A1 (6q12-q14), usually causing multiple epiphyseal dysplasia, has been reported to have autosomal recessive Stickler syndrome as well.  Homozygous individuals had typical ocular and auditory findings of autosomal dominant Stickler syndrome but with evidence of epiphyseal dysplasia.

Type I Stickler syndrome (108300, 609508) is an autosomal dominant disorder with somewhat similar ocular manifestations resulting from mutations in COL2A1.

Type II Stickler syndrome (604841) with a somewhat similar ocular phenotype is also an autosomal dominant disorder but caused by mutations in COL11A1.

Treatment Options

The myopia and hearing loss can be corrected.  Lifelong vigilance and prompt treatment are required for the vitreoretinal disease.

References

Baker S, Booth C, Fillman C, Shapiro M, Blair MP, Hyland JC, Ala-Kokko L. A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome. Am J Med Genet A. 2011 Jul;155(7):1668-72.

PubMed ID: 
21671392

Van Camp G, Snoeckx RL, Hilgert N, van den Ende J, Fukuoka H, Wagatsuma M, Suzuki H, Smets RM, Vanhoenacker F, Declau F, Van de Heyning P, Usami S. A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet. 2006 Sep;79(3):449-57.

PubMed ID: 
16909383

Glaucoma, Congenital Primary D

Clinical Characteristics

Ocular Features

Evidence of glaucoma can appear in early childhood but may appear much later.  However, typical signs such as enlarged corneas or frank buphthalmos, cloudiness of the corneas, tearing and photophobia are present only when the pressure is elevated due to pupillary block or when the lens migrates into the anterior chamber.  Most patients have additional signs such as ectopia lentis and spherophakia.

Systemic Features

Some patients have osteopenia, a high arched palate, and a marfanoid habitus.

Genetics

This form of congenital glaucoma has been described primarily in Middle Eastern and Asian as well as Roma/Gypsy families and is inherited in an autosomal recessive pattern.  The mutations occur in the LTBP2 gene (14q24) which is in close proximity to GLC3C, another putative gene with mutations causing congenital glaucoma. 

Mutations in other genes are also associated with primary congenital glaucoma such as in CYP1B1 causing type A (231300) and in GLC3B causing type B (600975).

THIS IS NOT A PRIMARY GLAUCOMA DISORDER.  Microspherophakia and ectopia lentis are not features of primary congenital glaucoma.  Elevated pressures in these patients are found only when there is a pupillary block or when the lens dislocates into the anterior chamber.  The enlarged cornea is clear and has no breaks in the Descemet membrane.  THIS CONDITION IS THEREFORE RECLASSIFIED AS “MEGALOCORNEA, ECTOPIA LENTIS, AND SPHEROPHAKIA”.     

Treatment Options

The usual surgical and pharmacological treatments for glaucoma apply but vision preservation is a challenge.  The spherophakic or dislocated lenses may need to be removed.

References

Azmanov DN, Dimitrova S, Florez L, Cherninkova S, Draganov D, Morar B, Saat R, Juan M, Arostegui JI, Ganguly S, Soodyall H, Chakrabarti S, Padh H, L??pez-Nevot MA, Chernodrinska V, Anguelov B, Majumder P, Angelova L, Kaneva R, Mackey DA, Tournev I, Kalaydjieva L. LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy founder population. Eur J Hum Genet. 2011 Mar;19(3):326-33.

PubMed ID: 
21081970

Ali M, McKibbin M, Booth A, Parry DA, Jain P, Riazuddin SA, Hejtmancik JF, Khan SN, Firasat S, Shires M, Gilmour DF, Towns K, Murphy AL, Azmanov D, Tournev I, Cherninkova S, Jafri H, Raashid Y, Toomes C, Craig J, Mackey DA, Kalaydjieva L, Riazuddin S, Inglehearn CF. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet. 2009 May;84(5):664-71.

PubMed ID: 
19361779

Wilson Disease

Clinical Characteristics

Ocular Features

The cornea and lens have visible copper deposition.  This is responsible for the classic (though non-pathognomonic) copper-colored Kayser-Fleischer ring in the cornea where evidence of copper deposition can be visualized in the posterior stroma and in the endothelium.  About 50-60% of patients at any point have evidence of such copper deposition but the number rises to 90% in patients with neurologic and psychiatric symptoms.  Copper deposition in the lens leads to a ‘sunflower’ or 'sunburst' cataract consisting of a greenish central disc in the anterior capsule with spoke-like radial cortical opacities.  Eye involvement in Wilson disease usually does not lead to significant impairment of vision.

Systemic Features

This is a disorder of copper metabolism.  It is associated with severe liver disease, often beginning with signs of recurrent jaundice, sometimes a hepatitis-like illness, and often culminating in liver failure.  Hepatobiliary malignancies are a significant risk, occurring in more than 1 percent of patients.  Neurologic toxicity leads to various movement disorders such as tremors, poor coordination, dystonia, and choreoathetosis.  Many patients have mental symptoms such as depression, neurotic behavior, and personality disturbances.  Some have a mask-like facies and pseudobulbar symptoms.  Symptoms can appear anytime from 3 years of age to over 50.  Other organs such as kidney, pancreas, heart and even joints may also be involved.

Patients often have a low serum ceruloplasmin, low copper levels, increased urinary excretion of copper, and increased concentration of copper in the liver.

Genetics

This is an autosomal recessive disorder caused by homozygous or doubly heterozygous mutations in the ATP7B gene (13q14.3).  Heterozygotes usually do not develop symptoms but may have reduced serum ceruloplasmin levels.

Treatment Options

Zinc and/or copper chelating agents such as D-penicillamine or trientine have long been used with benefit but the treatment must be used throughout life.  Reduced copper intake may also be helpful.  An orthotopic liver transplant can prolong life in selected patients.

References

Pfeiffenberger J, Mogler C, Gotthardt DN, Schulze-Bergkamen H, Litwin T, Reuner U, Hefter H, Huster D, Schemmer P, Czlonkowska A, Schirmacher P, Stremmel W, Cassiman D, Weiss KH. Hepatobiliary malignancies in Wilson disease. Liver Int. 2014 Nov 4. [Epub ahead of print].

PubMed ID: 
25369181

Ram J, Gupta A. Kayser-Fleischer Ring and Sunflower Cataract in Wilson Disease. JAMA Ophthalmol. 2014 May 8. [Epub ahead of print].

PubMed ID: 
24809467

Roberts EA, Schilsky ML; Division of Gastroenterology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada. A practice guideline on Wilson disease. Hepatology. 2003 Jun;37(6):1475-92. Erratum in: Hepatology. 2003 Aug;38(2):536.

PubMed ID: 
12774027

Dobyns WB, Goldstein NP, Gordon H. Clinical spectrum of Wilson's disease (hepatolenticular degeneration). Mayo Clin Proc. 1979 Jan;54(1):35-42.

PubMed ID: 
759736

Frommer D, Morris J, Sherlock S, Abrams J, Newman S. Kayser-Fleischer-like rings in patients without Wilson's disease. Gastroenterology. 1977 Jun;72(6):1331-5.

PubMed ID: 
558126