Diseases title

Nance-Horan syndrome )

Orpha Number: 627

Nance-Horan syndrome (NHS) is characterized by the association in male patients of congenital cataracts with microcornea, dental anomalies and facial dysmorphism. Prevalence is unknown. NHS is a rare but probably underdiagnosed disorder; 36 families have been reported in the literature. The ocular problem consists of congenital cataract (100% of cases), bilateral, usually severe, dense and most often total, associated with microcornea (96%), or even microphthalmia. In 93% of the cases, it is responsible for severe visual impairment evidenced by nystagmus (93%), sometimes associated with strabismus (43%). Dental abnormalities, although easily overlooked, are nearly constant, involve permanent and deciduous teeth and are of high diagnostic value. The most frequent are diastema, supernumerary incisors or posterior teeth, which are often impacted, and shape abnormalities (the most typical being screwdriver-shaped teeth). Facial dysmorphism is frequent and characterized by a long face, prognathism, a large nose, with a high nasal bridge, and large often protruding ears. Intellectual impairment is observed in about 30% of cases with inter- and intrafamilial variability. It is usually mild or moderate (80%), without motor delay, but in 20% of cases it is severe/profound and associated with autistic features. In heterozygote females, clinical manifestations are identical to those of affected males but they are attenuated and often limited to infraclinical findings. NHS is a genetic condition with X-linked semi-dominant transmission and high penetrance in heterozygote females. Causative mutations have been identified in the NHS gene (localized to Xp22.2) and typically result in a truncated protein. The differential expression of two NHS isoforms, NHS-A and NHS-1A, and differences in the subcellular localization of these isoforms may partly explain the various clinical manifestations. Diagnosis is based on clinical findings as there is no biological marker. The recognition of dental abnormalities requires careful physical and radiological dental examination. Differential diagnosis includes: X-linked microphthalmia, Lenz syndrome, Oculo-facio-cardio-dental (OFCD) syndrome, and Oculo-cerebro-renal (Lowe) syndrome (see these terms). Molecular study may be performed for the purpose of genetic counseling and antenatal diagnosis. Ocular abnormalities usually require surgery for cataract extraction although the results are poor. Complications (glaucoma, retinal detachment, etc) are treated medically or surgically depending on the type and severity. The ocular problem requires education appropriate for the degree of visual handicap and often necessitates education in a special school for the visually impaired. Dental anomalies may require orthodontic treatment. Intellectual impairment requires special education.
source: Orphanet