short limbs

Gracile Bone Dysplasia

Clinical Characteristics
Ocular Features: 

The eyes have been described as small.  Aniridia may be present.

Systemic Features: 

This is a usually fatal form of skeletal dysplasia with splenic and ocular features as well.  In utero death is not uncommon while newborns may not survive the neonatal period.  The face has been described as dysmorphic with a high forehead, flat nasal bridge, a cloverleaf-shaped skull, and hypoplastic cranial bones with premature suture closure.  The long bones are dysplastic as well with thinned diaphyses (sometimes fractured in utero), growth plate disorganization, excessive remodeling, and signs of arrested growth.  The ribs share in the dysplasia but pulmonary hypoplasia has also been described.  Most individuals have short limbs.

The spleen can be hypoplastic or aplastic and ascites has been noted in several infants.  Failure to thrive is common and seizures have been reported.  Males may have micropenis and hypospadias while females have been described with labial fusion.  

Low parathyroid hormone levels and hypocalcemia has been reported in most individuals.

Genetics

Heterozygous mutations in the FAM111A gene (11q12.1) have been associated with this disorder.  The functional role of FAM111A products is unknown but likely play a role in calcium metabolism, parathyroid hormone secretion, and osseous development.

Mutations in the same gene can be responsible for the allelic autosomal dominant Kenny-Caffey syndrome (127000) with some similar features.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

FAM111A mutations result in hypoparathyroidism and impaired skeletal development

Unger S, Gorna MW, Le Bechec A, Do Vale-Pereira S, Bedeschi MF, Geiberger S, Grigelioniene G, Horemuzova E, Lalatta F, Lausch E, Magnani C, Nampoothiri S, Nishimura G, Petrella D, Rojas-Ringeling F, Utsunomiya A, Zabel B, Pradervand S, Harshman K, Campos-Xavier B, Bonafe L, Superti-Furga G, Stevenson B, Superti-Furga A. FAM111A mutations result in hypoparathyroidism and impaired skeletal development. Am J Hum Genet. 2013 Jun 6;92(6):990-5.

PubMed ID: 
23684011

Keratoconus Posticus Circumscriptus

Clinical Characteristics
Ocular Features: 

The posterior corneal surface has area(s) of excavation (indentation) associated with overlying opacification.  The lens-corneal separation is reduced and iridocorneal adhesions are often present.  The clinical picture has been described as ‘posterior conical cornea’ or posterior keratoconus.

Systemic Features: 

The neck is short and has webbing.  The facies appear ‘coarse’, the posterior hairline is low, the nose is prominent, digits are short, and the vertebral anomalies may lead to scoliosis.  Individuals are short of stature and brachydactyly is often present.  Developmental delays and mental retardation are usually features.  Other variable anomalies have been reported.

Genetics

Autosomal recessive inheritance seems most likely in view of the family patterns.  Based on the few families reported, it is uncertain if this is a single entity with variable expression or a combination of disorders.  No gene or locus has been associated with this condition.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment beyond surgical repair of the cleft lip and palate or scoliosis is available.  Peripheral iridotomies have been done in the presence of shallow anterior chambers.

References
Article Title: 
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