OOA (Old Order Amish)

Inheritance: autosomal dominant
Genes: FGFR2

JWS
Kuhns toe
Acrocephalosyndactyly

Craniosyntosis
Midface hypoplasia
Enlarged great toe
Foot abnormalities
Proptosis

Jackson-Weiss Syndrome

Clinical Characteristics

General description (for patients):

This is a syndrome with face and foot abnormalities. A large kindred of Amish in Northern Indiana was reported by Jackson and coworkers in 1976 but there are probably more cases in at least Ohio and Wisconsin based on earlier reports. The clinical picture is variable but virtually all individuals have some clinical or X-ray abnormalities of the feet with enlarged, broad toes and often some webbing of the toes. The first toe may be turned inward. The midface is often flattened, leading to prominence of the eyes and the forehead. There may be premature closure of the cranial bones that results in deformities of the skull. If the latter is not corrected there is the risk of brain damage and sometimes damage to the optic nerves with permanent loss of vision. The hands are normal.

Medical description:

This form of acrocephalosyndactyly seems to be distinct from others in the absence of hand abnormalities such as those seen in Pfeiffer’s syndrome. In fact, some individuals have only malformations of the feet without cranial manifestations. Premature closure of the cranial sutures may lead to severe deformities of the skull but Jackson, et al found no evidence that this leads to brain damage or optic atrophy and suggested that cranial surgery is only indicated for cosmetic reasons, if at all. However, Cross and Opitz reported two related pedigrees from Ohio and Wisconsin with individuals that may have had the same disorder in which CNS damage occurred in some. In their Ohio pedigree, which suggested autosomal recessive inheritance, several children had delayed neurologic maturation. In the Wisconsin family, multigenerational abnormalities were more consistent with autosomal dominant inheritance and the cranial malformations were more consistent with Crouzon’s disease. Dilation of the frontal horns and optic atrophy were documented. No abnormalities of the great toes were reported but some individuals have webbing between the second and third toes. The nosological status of these families remains uncertain but it seems likely that several forms of craniosynostosis occur in the Amish.

Genetics:

The Jackson-Weiss syndrome is an autosomal dominant disorder due to a mutation (1043C>G) in the fibroblast growth factor receptor-2 (FGFR2) gene located on chromosome 10 (10q26). Interestingly,  several other mutations responsible for Crouzon syndrome map to the same gene locus.

Treatment:

The foot malformations cause little functional difficulties. From the study of Jackson, et al, no treatment is indicated for the craniofacial deformities.

Prognosis:

Normal lifespan.

Ancillary treatments and support:

It would seem wise to do appropriate radiographic studies in all patients with premature closure of cranial sutures. Likewise, periodic optic nerve examinations and visual fields should be done to enable timely intervention in cases with elevated intracranial pressure.

Specialists and specialty centers:

Neurologist, neurosurgeon, ophthalmologist.

References:

Jackson, C.E., Weiss, L., Reynolds, W.A., Forman, T.F., and Peterson, J.A.: Craniosynostosis, midface hypoplasia, and foot abnormalities: an autosomal dominant phenotype in a large Amish kindred. J. Pediat. 88: 963-968, 1976. PubMed ID: 1271196

Cross, H.E., and Opitz, J.M.: Craniosynostosis in the Amish. J. Pediat. 75: 1037-1044, 1969.

Heike, C., Seto, M., Hing, A., Palidin, A., Hu, F., Preston, R.A., Ehrlish, G.D., and Cunningham, M.: Century of Jackson-Weiss syndrome: further definition of clinical and radiographic findings in ‘lost’ descendants of the original kindred. Am. J. Med. Genet. 100: 315-324, 2001.  PubMed ID: 11343323

Jabs EW, Li X, Scott AF, Meyers G, Chen W, Eccles M, Mao JI, Charnas LR, Jackson CE, and Jaye M. (1994) Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nature Genetics 8(3): 275-279.  PubMed ID: 7874170

Resources:

Genetics Home Reference
About.com Rare Diseases

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