Study of Skeletal Disorders and Short Stature
Study of Skeletal Disorders and Short Stature
This study will determine the genes responsible for skeletal dysplasias (disorders of the
 skeleton) and short stature and define the range and type of medical problems they cause over
 time. It will investigate whether specific gene changes cause specific medical problems in
 these disorders and identify the signs and symptoms upon which their diagnoses must be based.

 Individuals with short stature or with a skeletal dysplasia known or suspected to be caused
 by a gene mutation (change) may be eligible for this study. Family members may also
 participate. Skeletal dysplasias under study include: achondroplasia, hypochondroplasia,
 achondrogenesis type II, hypochondrogenesis, Kniest dysplasia, spondyloepiphyseal dysplasias,
 Stickler syndrome; Shmid and Jansen metaphyseal dysplasias; pyknodysotosis, proximal
 symphalangism, brachydactyly types B C and E, Ellis van Creveld and related disorders,
 metatrophic chondrodysplasias, cartilage-hair hypoplasia and disorders with a skeletal
 abnormality that have not yet been defined but might be the result of a genetic defect.

 Patients will talk with two genetics specialists who will explain the study and its possible
 implications for the patient and family and answer questions. The patient's medical records
 will be reviewed, a personal and family history will be taken, and a physical examination
 will be done. Various other procedures that may be done include drawing up to 6 tablespoons
 of blood, some of which will be used for DNA (genetic) studies, X-rays, echocardiography
 (ultrasound of the heart), magnetic resonance imaging (MRI), eye examination, hearing test,
 sleep study, sperm analysis and skin biopsy (surgical removal of a small piece of skin done
 under local anesthetic). There may be additional evaluations by specialists in rheumatology,
 rehabilitation medicine and orthopedics. When the tests and examinations are completed (after
 2 to 3 days), a doctor will discuss the results with the patient. Patients whose DNA studies
 show that a gene change is responsible for their disorder will meet with a genetics nurse or
 counselor to review the results, express their feelings and ask any questions they may have.
 Patients may be asked to return to NIH every 6 months to 2 years for continued follow-up.
 Medical management will be provided primarily by the patient's own physician.

 Participating family members will be interviewed by telephone about their personal and family
 health history and will have a blood sample drawn for DNA testing. If a gene change is found
 that is responsible for the bone disorder or growth problem in the family, arrangements will
 be made for the family member to discuss the implications of the findings with a genetics
 specialist.
We will investigate the clinical manifestations and molecular genetic defects of human
 skeletal dysplasias and generalized short stature. Families with skeletal dysplasias or short
 stature of known or suspected genetic basis will be enrolled. Affected individuals or
 individuals suspected of having a skeletal dysplasia will undergo periodic clinical
 assessment and genetic analyses for the purpose of: 1) definition and characterization of
 phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype
 correlation. Genetic linkage studies may be performed for disorders in which the genetic
 bases is not yet known.
Patients with known or suspected skeletal dysplasias or short stature and their family
 members of any age will be recruited worldwide from diverse medical communities including
 genetics, orthopedics, ophthalmology, and pediatrics.

 DISEASE CATEGORY I:

 Individuals and family members with a suspected or an established diagnosis of any FGFR3
 disorder, type II collagen disorder, Schmid metaphyseal dysplasia, pyknodysostosis,
 proximal symphalangism, or brachydactyly type C.

 DISEASE CATEGORY II:

 Individuals and family members with a suspected or an established diagnosis of a skeletal
 dysplasia in which the disease gene is not yet known, including: Ellis van Crevald,
 brachydactyly types B and E, and cartilage-hair hypoplasia.

 DISEASE CATEGORY III:

 Individuals and family members who have previously uncharacterized systemic manifestations
 suggestive of a skeletal dysplasias, with clinical findings of: disproportionate or
 proportionate short stature; and/or cleft palate; and/or detached retina; and/or history of
 loose joints or frequent joint dislocation; and/or history of, or family history of,
 premature arthritis.

 Short Stature Category I: Individuals with generalized short stature and their family
 members. This includes adults with abnormal stature as statistically defined from
 standardized growth charts.

 Must be able to give informed consent, older children (greater than or equal to 7 years
 old) who do not give assent, or persons who are wards of the state will be excluded from
 the study.