joint dislocations

Joint Laxity, Short Stature, and Myopia

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

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
Treatment
Treatment Options: 

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

References
Article Title: 

GZF1 Mutations Expand the Genetic Heterogeneity of Larsen Syndrome

Patel N, Shamseldin HE, Sakati N, Khan AO, Softa A, Al-Fadhli FM, Hashem M, Abdulwahab FM, Alshidi T, Alomar R, Alobeid E, Wakil SM, Colak D, Alkuraya FS. GZF1 Mutations Expand the Genetic Heterogeneity of Larsen Syndrome. Am J Hum Genet. 2017 May 4;100(5):831-836.

PubMed ID: 
28475863

Ehlers-Danlos Syndrome, Type VIA

Clinical Characteristics
Ocular Features: 

The globe is thin and fragile and ruptures easily.  This results from scleral fragility which is in contrast to type VIB EDS  (229200) in which the cornea seems to be more fragile.  Retinal detachment is always a risk but no quantitative assessment can be made since early case reports did not always provide good classification of EDS types.  Other ocular abnormalities such as keratoconus and structural changes in the cornea are less common but frequent changes in classification and lack of genotyping in early cases make definitive clinical correlations difficult.

Systemic Features: 

The primary clinical manifestations of this form (VIA) of Ehlers-Danlos syndrome are extraocular.   The skin is soft, thin, easily extensible, and bruises easily.  The joints are highly flexible with a tendency to dislocate.  Arterial ruptures are not uncommon, often with severe consequences.  Scoliosis begins almost at birth and often progresses to severe kyphoscoliosis.  Patients are floppy (hypotonic).  Intellect is normal and there are generally no developmental delays.  Thirty per cent of infants have a club foot at birth.

Genetics

This an autosomal recessive disorder caused by molecular defects in the PLOD1 gene (1p36.3-p36.2).  The gene product is an enzyme, lysyl hydroxylase 1, important for the normal crosslinking of collagen. Mutations in PLOD1 may result in hydroxylase dysfunction with abnormal hydroxylation of lysine, weakened crosslinks, and fragile tissue.  

The classification of Ehlers-Danlos disease is under constant revision as new mutations and clinical subtypes are found (see 130000).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Joint dislocations, ocular trauma and vascular ruptures require prompt attention.  Longevity is not impacted by this syndrome.

References
Article Title: 
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