Alternative titles; symbols
ORPHA: 808; DO: 0070013;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 18q11.2 | Seckel syndrome 2 | 606744 | Autosomal recessive | 3 | RBBP8 | 604124 |
A number sign (#) is used with this entry because of evidence that Seckel syndrome-2 (SCKL2) is caused by homozygous mutation in the RBBP8 gene (604124) on chromosome 18q11.
Jawad syndrome (251255), a microcephaly syndrome involving impaired intellectual development and digital anomalies, is also caused by mutation in the RBBP8 gene.
Seckel syndrome (SCKL) is a rare autosomal recessive disorder characterized by growth retardation, microcephaly with impaired intellectual development, and a characteristic facial appearance (Borglum et al., 2001).
For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600).
Borglum et al. (2001) studied a consanguineous family of Iraqi descent with Seckel syndrome. The parents were first cousins and had 4 children who fulfilled the criteria for Seckel syndrome, as well as a younger healthy girl. Borglum et al. (2001) mapped the locus in this family to chromosome 18 and noted a number of distinct differences between this family and individuals in chromosome 3-linked families with Seckel syndrome (SCKL1; 210600). The mental and motor retardation in the chromosome 18-linked family was milder. The growth retardation of the chromosome 18-linked patients was proportionate, whereas in the chromosome 3-linked families, the heads were small relative to other parameters. All affected sibs in the chromosome 18-linked family had one or more small cafe-au-lait spots on the skin, a finding not previously reported in Seckel syndrome. This finding suggested to the authors that the underlying defect in these patients might involve DNA repair.
Shaheen et al. (2014) studied a 9-year-old Saudi Arabian girl with short stature (height -6.2 SD below mean) who was underweight (weight -4.2 SD below mean) and also had microcephaly (head circumference -4.1 SD below mean), microphthalmia, micrognathia, microglossia, small teeth, and limited supination of upper extremities. Brain MRI showed calcification of the bilateral basal ganglia and cerebellum.
Borglum et al. (2001) studied a consanguineous family of Iraqi descent with Seckel syndrome. A maximum multipoint lod score of 3.1 was obtained to markers proximal on chromosome 18 and with a region of overlapping homozygosity in the 4 affected children between the markers D18S78 and D18S866, corresponding to an approximately 30-cM transcentromeric region, 18p11.31-q11.2.
The transmission pattern of Seckel syndrome in the family reported by Qvist et al. (2011) was consistent with autosomal recessive inheritance.
In a consanguineous Iraqi family with Seckel syndrome mapping to chromosome 18p11.31-q11.2, previously studied by Borglum et al. (2001), Qvist et al. (2011) sequenced the candidate gene RBBP8 and identified homozygosity for a splice site mutation (604124.0001) that segregated with the disease and was not found in 100 controls.
In a 9-year-old Saudi Arabian girl with Seckel syndrome, Shaheen et al. (2014) identified homozygosity for a missense mutation in the RBBP8 gene (R100W; 604124.0004).
Borglum, A. D., Balslev, T., Haagerup, A., Birkebaek, N., Binderup, H., Kruse, T. A., Hertz, J. M. A new locus for Seckel syndrome on chromosome 18p11.31-q11.2. Europ. J. Hum. Genet. 9: 753-757, 2001. [PubMed: 11781686] [Full Text: https://doi.org/10.1038/sj.ejhg.5200701]
Qvist, P., Huertas, P., Jimeno, S., Nyegaard, M., Hassan, M. J., Jackson, S. P., Borglum, A. D. CtIP mutations cause Seckel and Jawad syndromes. PLoS Genet. 7: e1002310, 2011. Note: Electronic Article. [PubMed: 21998596] [Full Text: https://doi.org/10.1371/journal.pgen.1002310]
Shaheen, R., Faqeih, E., Ansari, S., Abdel-Salam, G., Al-Hassnan, Z. N., Al-Shidi, T., Alomar, R., Sogaty, S., Alkuraya, F. S. Genomic analysis of primordial dwarfism reveals novel disease genes. Genome Res. 24: 291-299, 2014. [PubMed: 24389050] [Full Text: https://doi.org/10.1101/gr.160572.113]