Recent studies have found that Phospho1 KO mice (Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis.
Human patients with heterozygous microdeletions in the MIR17HG locus have autosomal dominant Feingold syndrome, characterized by multiple skeletal abnormalities in the fingers and toes, short stature and microcephaly.
In the pregnancies not terminated electively, 11 (17%) ended in miscarriage, and of the 33 that proceeded to delivery, four children (12%) had congenital anomalies, including one child with multiple skeletal abnormalities [ 149].
Loss-of-function mutations in GPC3 cause Simpson-Golabi Behmel syndrome (MIM 312870), an overgrowth syndrome with multiple skeletal abnormalities (large protruding jaw, widened nasal bridge, upturned nasal tip, and broad, short hands and fingers) that is associated with increased cell proliferation [ 59].
Patients are characterized by moderate mental retardation and multiple congenital anomalies, including mild craniofacial and skeletal abnormalities, behavioral abnormalities, sleep disturbances, a short stature, and cardiac and renal malformations.
Interestingly, these mice showed severe abnormalities of chondrocyte and osteoblast differentiation and developed multiple skeletal defects that are not observed in the adult induced SHP-2-deficient model, including growth retardation, limb and chest skeletal abnormalities, and calvarial defects.
For example, in Kabuki syndrome, a dominantly inherited multiple malformation disorder characterized by a distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability, among 32 disease mutations found in 53 families, 27 (20 nonsense mutations and 7 indels) resulted in a premature stop codon [ 11, 48].
Using multivariate analysis, the primary tumor group, visceral or cerebral metastases, abnormality of laboratory data, ECOG PS 3 or 4 grade, previous chemotherapy, and multiple skeletal metastases were found to be significantly independent prognostic factors (Table 3).
The resulting risk of mental retardation, eye problems, skeletal abnormalities and stroke can be reduced by a special diet and high doses of vitamin B6 or B12.
This is especially intriguing because Kennedy's autopsy report found "no significant gross skeletal abnormalities," aside from the bullet wounds in the skull.
Adrenal corticosteroid hormone is associated with skeletal abnormalities, osteopenia, and osteonecrosis.
