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
Inheritance
This is an X-linked recessive (dominant?) disorder resulting from mutations in the NHS 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 (CXN; 302200) 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 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.
Pedigree
X-linked recessive, carrier mother
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked recessive, father affected
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.