Alternative titles; symbols
ORPHA: 166024;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q26.1 | ?Al-Gazali-Bakalinova syndrome | 607131 | Autosomal recessive | 3 | KIF7 | 611254 |
A number sign (#) is used with this entry because of evidence that Al-Gazali-Bakalinova syndrome (AGBK) is caused by homozygous mutation in the KIF7 gene (611254) on chromosome 15q26. One such family has been reported.
Al-Gazali-Bakalinova syndrome (AGBK) is characterized by multiple epiphyseal dysplasia, macrocephaly, and distinctive facial features including frontal bossing, hypertelorism, flat malar regions, low-set ears, and short neck. Other features include pectus excavatum, spindle-shaped fingers, clinodactyly, prominent joints, and genu valgum (summary by Ali et al., 2012).
Bayoumi et al. (2001) described linkage analysis in an Omani family previously described by al-Gazali and Bakalinova (1998). The pedigree consisted of 13 children in 2 sibships of a multiply consanguineous family. Four of the children were affected. The presenting features were dysmorphic facies, genu valgum, and swelling of the joints. All 4 children were of normal stature with head circumference above the 90th percentile. The children had frontal bossing, hypertelorism, flattening of the malar region, and low-set ears. The neck was short, and pectus excavatum, spindle-shaped fingers with interdigital soft-tissue webbing, and clinodactyly were present. All had genu valgum with prominent joints, particularly the wrist, knee, and ankle joints. Skeletal surveys showed dysplasia of the epiphyses of the long bones which was more severe in the lower limbs than the upper limbs. In 2 children, brain imaging was available and showed agenesis of the corpus callosum and frontotemporal brain atrophy.
Karaer et al. (2012) described what they considered to be the second report of this disorder, which they called Al-Gazali-Bakalinova syndrome, in a macrocephalic male, born to consanguineous parents, with facial anomalies, cranial MRI findings, and multiple epiphyseal dysplasia. The patient had the additional features of pectus carinatum, hip dislocation, and a history of prenatal polyhydramnios.
Bayoumi et al. (2001) performed linkage analysis on the family described by al-Gazali and Bakalinova (1998) and showed a 2-point lod score of zeta = +3.45 for the marker locus D15S127. Haplotype analysis defined a homozygous region of 32.2 cM between markers D15S205 and D15S966 within which the aggrecan (ACAN; 155760) gene lies. Single-nucleotide polymorphism (SNP) analysis excluded this gene as a candidate for the phenotype in this family and redefined the critical region to 28.1 cM between D15S1046 and D15S966.
Bayoumi et al. (2001) suggested that the pedigree in the family originally reported by al-Gazali and Bakalinova (1998) demonstrated autosomal recessive inheritance.
By whole-exome sequencing in the family with macrocephaly, multiple epiphyseal dysplasia, and distinctive facies described by al-Gazali and Bakalinova (1998), Ali et al. (2012) identified homozygosity for a missense mutation (N1060S; 611254.0009) in the KIF7 gene. The mutation segregated with the phenotype in the family and was absent from 188 mixed Omani/UAE ethnically matched controls. The N1060 residue is located after the SMC domain of KIF7 and is absolutely conserved in KIF7 family members. Hamosh (2016) noted that the N1060S variant was not present in the ExAC database (1/21/16).
al-Gazali, L. I., Bakalinova, D. Autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance. Clin. Dysmorph. 7: 177-184, 1998. [PubMed: 9689990] [Full Text: https://doi.org/10.1097/00019605-199807000-00004]
Ali, B. R., Silhavy, J. L., Akawi, N. A., Gleeson, J. G., Al-Gazali, L. A mutation in KIF7 is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance. Orphanet J. Rare Dis. 7: 27, 2012. Note: Electronic Article. [PubMed: 22587682] [Full Text: https://doi.org/10.1186/1750-1172-7-27]
Bayoumi, R., Saar, K., Lee, Y.-A., Nurnberg, G., Reis, A., Nur-E-Kamal, M., Al-Gazali, L. I. Localisation of a gene for an autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia, and distinctive facies to chromosome 15q26. J. Med. Genet. 38: 369-373, 2001. [PubMed: 11389160] [Full Text: https://doi.org/10.1136/jmg.38.6.369]
Hamosh, A. Personal Communication. Baltimore, Md. 1/21/2016.
Karaer, K., Rosti, R. O., Torun, D., Sanal, H. T., Guran, S. Macrocephaly with multiple epiphyseal dysplasia: a second example of Al Gazali-Bakalinova syndrome? Genet. Counsel. 23: 457-463, 2012. [PubMed: 23431744]