Alternative titles; symbols
SNOMEDCT: 719304005; ORPHA: 93316; DO: 0112296;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q13.11 | Spondylometaphyseal dysplasia, Algerian type | 184253 | Autosomal dominant | 3 | COL2A1 | 120140 |
A number sign (#) is used with this entry because of evidence that the Algerian type of spondylometaphyseal dysplasia (SMDALG) is caused by heterozygous mutation in the COL2A1 gene (120140) on chromosome 12q13.
The Algerian type of spondylometaphyseal dysplasia (SMDALG) is an autosomal dominant disorder characterized by a short trunk and severe genu valgum. Myopia may be present. The radiologic hallmarks include moderate platyspondyly, particularly with dorsal vertebral flattening, and short ilia with narrow greater sciatic notches. There is generalized metaphyseal dysplasia of the long bones, most conspicuous in the hip and knee and associated with coxa vara and severe genu valgum. The short tubular bones are mildly affected, and epiphyses of the tubular bones are said to be normal (Matsubayashi et al., 2013).
Kozlowski et al. (1988) reported an Algerian family in which a father and 5 of his 12 children had a seemingly 'new' form of spondylometaphyseal dysplasia. Examination of 5 affected family members revealed dwarfism, genu valgum deformity, progressive kyphoscoliosis, wrist deformity, and severe metaphyseal dysplasia, with moderate spinal changes and minimal changes in the hands and feet. All had myopia. The authors noted that none of the spondylometaphyseal dysplasias show a combination of such severe metaphyseal changes and severe genu valgum. Among the metaphyseal dysplasias, only the Jansen type (156400) shows severe metaphyseal changes, but in that disorder genu varus deformity is found and sclerosis of the skull is a common finding in older patients (Holthusen et al., 1975).
Rybak et al. (1991) described a 12-year-old boy with short stature and progressive deformity of the legs. Examination showed a marked valgus deformity at the knees, hyperlordosis, and minimal scoliosis. Ophthalmologic examination revealed myopia. Radiographs showed moderate platyspondyly, with generalized metaphyseal changes most marked in the long tubular bones. The short tubular bones were minimally affected. Some dysplastic/hypoplastic changes were noted in the epiphyses, round bones, and acetabulae, but were much less prominent than those of the spine and metaphyses. No other family members were affected. The authors stated that the condition was identical to that of the affected individuals in the Algerian family reported by Kozlowski et al. (1988). Rybak et al. (1991) also suggested that the patient reported by Schmidt et al. (1963) had the same disorder.
Matsubayashi et al. (2013) reported an 8-year-old Japanese boy with the Algerian type of spondylometaphyseal dysplasia and mutation in the COL2A1 gene. At birth the proband was noted to have generalized skeletal changes as well as soft palate clefting and micrognathia, requiring tube feeding. At age 7 he exhibited marked short stature and severe deformity of the legs. Examination revealed hyperlordosis with minimal scoliosis, short trunk, and severe genu valgum. Ophthalmologic examination revealed myopia, and he had hearing impairment with bilateral ear canal stenosis. His Wechsler Intelligence Scale for Children was scored as 70. Radiologic imaging showed platyspondyly with dorsal vertebral flattening, broad and short ilia with narrow greater sciatic notches, irregular iliac crests and acetabula, coxa vara, and short femoral necks. The proximal femoral epiphyses were mottled, with horizontal clefts. Genu valgum was marked on the left. Short tubular bones were minimally affected. Assessment at 8 years of age showed normalization of the proximal femoral epiphyses with progressive ossification, and the authors noted that the phenotype was consistent with SMDALG.
Cammarata-Scalisi et al. (2023) reported a 5-year-old Venezuelan boy with SEMDALG and mutation in the COL2A1 gene. The proband had severe short stature, with a short neck and trunk and severe dorsolumbar scoliosis with lumber hyperlordosis. His femora were held in flexion and he exhibited a windswept deformity of the knees. He also had brachydactyly and camptodactyly. Cognitive development was within the normal range, and ophthalmologic and auditory examinations were normal. X-rays showed platyspondyly, dorsolumbar scoliosis, and lumbar hyperlordosis. The ilia were broad and short, and the proximal femoral epiphyses were in severe varus position and mottled in appearance. The right knee was in valgus position, and the left mildly bowed. The metaphyseal margins of the long bones were irregular with intermingled radiolucencies and radiodensities. Corner fractures were present. Short tubular bones were minimally affected.
In an 8-year-old Japanese boy with spondylometaphyseal dysplasia consistent with the Algerian type, Matsubayashi et al. (2013) sequenced the COL2A1 gene and identified a heterozygous missense mutation (G861V; 120140.0057). The mutation was not found in 50 Japanese controls or in the SNP database. The proband's nonconsanguineous parents and 2 older sisters were healthy, but familial DNA was not available for segregation analysis. Noting similarities between spondyloepimetaphyseal dysplasia of the Strudwick type (SEMDSTWK; 184250) and SMDALG, the authors stated that SEMDSTWK patients 2 and 3 of Walter et al. (2007), had manifestations 'identical' to the Japanese boy, except for genu varum in the former and genu valgum in the latter. Matsubayashi et al. (2013) suggested that SEMDSTWK and SMDALG might represent phenotypic variation of a single disorder.
In a 5-year-old Venezuelan boy with SEMDALG, Cammarata-Scalisi et al. (2023) screened the COL2A1 gene and identified 2 variants: the first was a 'clearly pathogenic' missense mutation (G1092D; 120140.0058), and the second was a 'potentially pathogenic' intronic variant (c.1366-13C-A; rs200984998). DNA was unavailable from his unaffected nonconsanguineous parents for segregation analysis. The authors noted that the intronic variant was present in the 1000 Genomes Project Phase 3 database in heterozygous state in the Colombian population with a minor allele frequency of 0.011, and that the paternal grandparents of the proband were from Colombia.
Cammarata-Scalisi, F., Matysiak, U., Willoughby, C. E., Ruzaike, G., Cardenas Tadich, A., Araya Castillo, M., Zara-Chirinos, C., Bracho, A., Avendano, A., Jilani, H., Callea, M. A severe case of spondylometaphyseal dysplasia Algerian type with two mutations in COL2A1. J. Pediat. Genet. 12: 339-341, 2023. [PubMed: 38162154] [Full Text: https://doi.org/10.1055/s-0041-1732474]
Holthusen, W., Holt, J. F., Stoeckenius, M. The skull in metaphyseal chondrodysplasia type Jansen. Pediat. Radiol. 3: 137-144, 1975. [PubMed: 1233427] [Full Text: https://doi.org/10.1007/BF01006898]
Kozlowski, K., Bacha, L., Massen, R., Ayati, M., Sator, S., Brahimi, L. A new type of spondylo-metaphyseal dysplasia--Algerian type: report of five cases. Pediat. Radiol. 18: 221-226, 1988. [PubMed: 3368247] [Full Text: https://doi.org/10.1007/BF02390399]
Matsubayashi, S., Ikema, M., Ninomiya, Y., Yamaguchi, K., Ikegawa, S., Nishimura, G. COL2A1 mutation in spondylometaphyseal dysplasia Algerian type. Molec. Syndromol. 4: 148-151, 2013. [PubMed: 23653587] [Full Text: https://doi.org/10.1159/000346644]
Rybak, M., Foley, T. P., Kozlowski, K. Spondylo-metaphyseal dysplasia Algerian type: confirmation of a new syndrome. Am. J. Med. Genet. 40: 304-306, 1991. [PubMed: 1951433] [Full Text: https://doi.org/10.1002/ajmg.1320400311]
Schmidt, B. J., Becak, W., Becak, M. L., Soibelman, I., da Silva Queiroz, A., Lorga, A. P., Secaf, F., Antonio, C. F., Carvalho, A. A. Metaphyseal dysostosis: review of literature; study of a case with cytogenetic analysis. J. Pediat. 63: 106-112, 1963. [PubMed: 13991956] [Full Text: https://doi.org/10.1016/s0022-3476(63)80308-x]
Walter, K., Tansek, M., Tobias, E. S., Ikegawa, S., Coucke, P., Hyland, J., Mortier, G., Iwaya, T., Nishimura, G., Superti-Furga, A., Unger, S. COL2A1-related skeletal dysplasias with predominant metaphyseal involvement. Am. J. Med. Genet. A 143A: 161-167, 2007. [PubMed: 17163530] [Full Text: https://doi.org/10.1002/ajmg.a.31516]