Nance-Horan Syndrome

Clinical Characteristics

Ocular Features:

Congenital cataracts are a feature of this X-linked disorder. These consist of bilateral, dense nuclear opacification (in most males) but sutural opacities are also seen, especially in carrier females. If the nuclear cataracts are not treated promptly, severe amblyopia, nystagmus, and strabismus may result. Microcornea, congenital glaucoma, scleral staphylomas, and retinal cystoid degeneration may also be present. Microphthalmia has been described. These ocular signs are present in 90% of heterozygous females but they may be subtle and careful examination is required to identify them. Cataract surgery is usually not required in females.

Systemic Features:

This is a developmental disorder in which facial dysmorphism and dental anomalies are consistent systemic features in affected males. Some patients (30%) also have some intellectual impairment while others have developmental delays and behavior problems. The pinnae may be anteverted and often appear large while the nose and nasal bridge are prominent. The teeth in males are small and pointed or 'screwdriver shaped' and are widely separated (sometimes called Hutchinson teeth). The enamel may be hypoplastic and dental agenesis can be present. Supernumerary incisors have been described. The facial and dental features may be present in female carriers but are less pronounced. Females do not have intellectual impairment.

Genetics

This is an X-linked recessive (dominant?) disorder resulting from mutations in the NHS [1] gene located at Xp22.13. However, heterozygous females may have clinical manifestations, including dense cataracts, and all offspring of such females need ophthalmological evaluations at birth.

It is likely that at least some cases of X-linked congenital cataract [2] (CXN; 302200 [3]) represent this disorder because the facial dysmorphism may be subtle and easily missed in Nance-Horan. Of course, the two disorders may also be allelic. A variety of alterations in the NHS [1] gene, including copy number variations, intragenic deletions, and duplication/triplication arrangements, have been found. The occasionally subtle facial dysmorphology and the dental abnormalities are easily missed in patients in whom congenital cataracts are the primary clinical concern.

Treatment

Treatment Options:

Visually significant cataracts should be removed early to allow for normal visual maturation. Glaucoma must be treated appropriately. At risk males and females should have dental X-rays and dental surgery may be required. Special education may be beneficial in males.

References

Article Title:

Ophthalmic pathology of Nance-Horan syndrome: case report and review of the literature [4]

Ding X, Patel M, Herzlich AA, Sieving PC, Chan CC. Ophthalmic pathology of Nance-Horan syndrome: case report and review of the literature. Ophthalmic Genet. 2009 Sep;30(3):127-35.

PubMed ID:

19941417

X-linked cataract and Nance-Horan syndrome are allelic disorders [5]

Coccia M, Brooks SP, Webb TR, Christodoulou K, Wozniak IO, Murday V, Balicki M, Yee HA, Wangensteen T, Riise R, Saggar AK, Park SM, Kanuga N, Francis PJ, Maher ER, Moore AT, Russell-Eggitt IM, Hardcastle AJ. X-linked cataract and Nance-Horan syndrome are allelic disorders. Hum Mol Genet. 2009 Jul 15;18(14):2643-55.

PubMed ID:

19414485

Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation [6]

Burdon KP, McKay JD, Sale MM, Russell-Eggitt IM, Mackey DA, Wirth MG, Elder JE, Nicoll A, Clarke MP, FitzGerald LM, Stankovich JM, Shaw MA, Sharma S, Gajovic S, Gruss P, Ross S, Thomas P, Voss AK, Thomas T, Gecz J, Craig JE. Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation. Am J Hum Genet. 2003 Nov;73(5):1120-30.

PubMed ID:

14564667