Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: ... Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most cases of OI are autosomal dominant with mutations in 1 of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Martinez-Glez et al. (2012) described osteogenesis imperfecta type XIII, an autosomal recessive form of the disorder characterized by normal teeth, faint blue sclerae, severe growth deficiency, borderline osteoporosis, and an average of 10 to 15 fractures a year affecting both upper and lower limbs and with severe bone deformity.
Martinez-Glez et al. (2012) described a sister and brother, offspring of first-cousin Egyptian parents, with autosomal recessive OI. The 15-year-old female proband had a triangular face, broad forehead, wide palpebral fissures, long eyelashes, faint blue sclerae, long philtrum, ... Martinez-Glez et al. (2012) described a sister and brother, offspring of first-cousin Egyptian parents, with autosomal recessive OI. The 15-year-old female proband had a triangular face, broad forehead, wide palpebral fissures, long eyelashes, faint blue sclerae, long philtrum, thin lips, and prominent ears. Gross motor development was delayed and she was not able to stand unsupported. No dentinogenesis imperfecta was present. Her thorax was relatively large with increased anteroposterior and transverse diameters compressing the abdomen. She had a large umbilical hernia with abdominal content, generalized hypotonia, muscle wasting, and nocturnal enuresis. Skeletal examination showed severe generalized deformities of all bones with consistent pain on touch, including deformed clavicles; bilateral bowed angulated humerus, radius, and ulna; arachnodactyly; and hyperextensibility of elbow, wrist, and interpahalangeal joints. Lower limbs showed bowing of femora, severely angulated deformed leg bones and limited movements of the knee joints. She also had kyphoscoliosis and pectus carinatum. Radiologic examination revealed deformed long bones with multiple fractures and callus formation, lack of bone modeling with wide distal metaphyses of femora, serpentine thin tibiae and fibulae in addition to S-curve scoliosis of thoracic and lumbar spine with platyspondyly, and generalized decreased bone density. Skull X-ray showed wormian bones. Anthropometric measurements at 13 years of age were below normal for weight (-3.8 SD), length (-11.5 SD) and head circumference (-3.0 SD). Bone densitometry (DEXA) at 15 years revealed borderline osteoporosis at the hip and spine (Z-score -2.22 and -2.13, respectively). Her 5-year-old brother had a similar phenotype. Audiologic and cardiovascular examinations of both patients were unremarkable. Serum calcium and phosphate were normal, whereas alkaline phosphatase levels were slightly high. Both patients were diagnosed as having Sillence type III, and cyclic IV bisphosphonate injections were started.
By direct sequencing of the BMP1 gene in a proband with severe autosomal recessive osteogenesis imperfecta and a large umbilical hernia, the offspring of consanguineous Egyptian parents, Martinez-Glez et al. (2012) identified homozygosity for a missense mutation in ... By direct sequencing of the BMP1 gene in a proband with severe autosomal recessive osteogenesis imperfecta and a large umbilical hernia, the offspring of consanguineous Egyptian parents, Martinez-Glez et al. (2012) identified homozygosity for a missense mutation in the BMP1 gene (F249L; 112264.0001). The same mutation was found in the proband's affected brother. Their parents and unaffected sibs were heterozygous for the mutation. In 2 affected sibs of a consanguineous family from Turkey with increased bone mineral density and multiple recurrent fractures, Asharani et al. (2012) identified homozygosity for a missense mutation (G12R; 112264.0002) in the BMP1 gene. The mutation was identified by combined whole-exome sequencing and filtering for homozygous stretches of identified variants.