OMIM ID:
Gracile Bone Dysplasia
Alternate Names
Defective Genes
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
Inheritance
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
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission