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Joint Laxity, Short Stature, and Myopia

OMIM ID:

autosomal recessive

Joint Laxity, Short Stature, and Myopia

Alternate Names

JLSM

Defective Genes

GZF1

Clinical Characteristics

Ocular Features

Three of four brothers in one family had high myopia and two had retinal detachments as well as iris and chorioretinal colobomas.  In a second family with five sibs a teenage female was reported to have glaucoma and vision of legal blindness.  She and one brother had high myopia as well (parameters not reported).

Systemic Features

In one consanguineous family a brother and sister had multiple large joint dislocations including elbows, hips, knees and ankles.  The sister exhibited severe kyphoscoliosis while her brother had only mild kyphosis.  A single individual in each of the two sibships had hearing loss.

Three brothers in another consanguineous family had joint laxity and mild pectus carinatum.

Short stature was noted in all 5 affected individuals.  Cognitive development was reported as normal.

Genetics

Inheritance

Five individuals from 2 consanguineous Saudi sibships have been reported.  Homozygous mutations in the GZF1 gene (20p11.21) segregated as expected for an autosomal recessive disorder.

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

No treatment has been reported.   Retinal detachment surgery and joint dislocation reduction should be considered in appropriate individuals.

Selected Resources

Web Resources

Publications

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GZF1 Mutations Expand the Genetic Heterogeneity of Larsen Syndrome

PubMedID: 28475863