Nance-Horan Syndrome
Patient Information
Characteristics
Background and History
In 1974 Margaret B. Horan, an Australian pediatrician, and Walter E. Nance, an American internist and geneticist independently described patients with this syndrome in which dental anomalies and cataracts are associated.
Clinical Correlations
Males are nearly always born with cataracts. These may be dense enough to severely impair vision and require early removal. Females frequently have some opacities in the lenses (cataracts) as well but these are usually mild and do not require surgery. The corneas (windshield of the eye) may be small. The facial morphology is unusual with prominent noses and large ears but this is less pronounced in females. The teeth are almost always malformed and anomalous in both sexes. They may be ‘screwdriver shaped’ or small and pointed. Extra teeth are often present but sometimes several are missing. The front teeth often have wide spaces between them (diastema).
About 30% of males have some intellectual impairment but this is not seen in females.
Genetics
Inheritance
This is an X-linked disorder in which males are the most severely affected but almost all female carriers have some signs upon careful examination. Thus, this disorder can be described as either an X-linked recessive or X-linked dominant disease. Affected males have a single X chromosome which is obligatorily transmitted to all of their daughters so that they become carriers if it contains the mutation. The other X chromosome in females usually does not have the mutation so they are usually more mildly affected. However, such carrier (heterozygous) females can expect that half of their sons will have the full syndrome while half their daughters will be carriers. Affected males cannot have affected sons.
Pedigree
X-linked dominant, father affected
X-linked inheritance patterns result when disease-causing mutations are located on the X chromosome. Males have one X chromosome while females have two. A mutation on the male's X chromosome frequently is lethal or renders him unable to reproduce. However, in rare cases when males have children, they can expect that all of then will inherit the condition.
X-linked inheritance patterns result when disease-causing mutations are located on the X chromosome. Males have one X chromosome while females have two. A mutation on the male's X chromosome frequently is lethal or at least renders them unable to reproduce. However, in rare cases when males have children, they can expect that all of then will inherit the condition.
X-linked dominant, mother affected
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
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.
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'.
Diagnosis and Prognosis
The diagnosis is usually made by an ophthalmologist when cataracts are found in infant boys but the full syndrome will often require collaboration with dental experts and medical geneticists. It is important that visually significant cataracts are removed early to allow full maturation of the visual system. All offspring in families with evidence of the Nance-Horan disorder should have complete eye examinations right after birth to detect these cataracts. Cataract surgery in young children is more difficult than in adults and complications such as glaucoma and retinal detachments may occur.
It is also useful to have full dental X-rays in children to look for dental anomalies so that corrective surgery is undertaken in a timely manner. Children with significant intellectual challenges can benefit from special education.
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