Joint Laxity, Short Stature, And Myopia

A number sign (#) is used with this entry because of evidence that joint laxity, short stature, and myopia (JLSM) is caused by homozygous mutation in the GZF1 gene (613842) on chromosome 20p11.

Clinical Features

Patel et al. (2017) studied 5 affected individuals from 2 consanguineous Saudi families with joint laxity, short stature, and severe myopia with prominent eyes. An affected sister and brother in the first family exhibited multiple joint dislocations, involving the elbows, hips, knees, and ankles, as well as pectus carinatum and talipes equinovarus. The 16-year-old sister had severe kyphoscoliosis with compromised lung function, and progressive hearing loss. Her 2.5-year-old brother had only mild cervical kyphosis and no hearing loss. In the second family, 3 affected brothers exhibited joint laxity and mild pectus carinatum; 1 brother also had mild scoliosis and another had bilateral talipes equinovarus. All 3 brothers had severe myopia, 2 of whom also had retinal detachment and iris and chorioretinal coloboma, and 1 brother had hearing loss. Patel et al. (2017) considered the phenotype in the 2 families to be consistent with an autosomal recessive form of Larsen syndrome (see 150250), although they observed a number of clinical and radiologic differences between their patients and previously reported patients. The authors stated that the most striking difference was the severe eye phenotype in their patients, noting that eye involvement is unusual in Larsen syndrome.

Molecular Genetics

By combined autozygome and exome sequencing in 2 consanguineous Saudi families with short stature, joint laxity, and severe myopia, Patel et al. (2017) identified homozygous mutations in the GZF1 gene: a nonsense mutation (E289X; 613842.0001) in one family and a frameshift mutation (613842.0002) in the other. The mutations were confirmed by Sanger sequencing and segregated fully with disease in each family. Neither mutation was found in 2,379 Saudi exomes or the ExAC database.