Chromosome 4q12q21 deletion E70.35

Chromosome 4q deletion syndrome is a rare neurogenic syndrome with intellectual disability that can occur with or without piebaldism. It is caused by a large number of non-recurrent deletions of 4q.

A whole genome genotyping analysis of a patient with piebaldism revealed a 1.34 Mb microduplication of 1q21.1q21.2 and a 2.7 Mb microdeletion of 4q12. The clinical and molecular findings in these subjects showed that the 2.7 Mb 4q12 microdeletion causes isolated piebaldism due to the loss of the KIT gene (Arasimavičius J et al. 2020).

The following symptoms may also occur with this phenotype:

Dolichocephaly, pectus excavatum, hip dysplasia, pes planus, myopia, lens opacities and the absence of spoken language, but not of communication through gestures.

Piebaldism may be absent in rare cases. This suggests that piebaldism may result from a more complex mechanism than a simple haploinsufficiency of KIT (Hemati P et al. 2015).

1. Arasimavičius J et al. (2020) A Familial 4q12 Deletion Involving KIT Gene Causes Piebaldism. Acta Dermatovenerol Croat 28:105-108.
2. Fujimoto A et al. (1998) Interstitial deletion of chromosome 4, del(4)(q12q21.1), in a mentally retarded boy with a piebald trait, due to maternal insertion, ins(8;4). Am J Med Genet 75:78-81.
3. Hemati P et al. (2015) 4q12-4q21.21 deletion genotype-phenotype correlation and the absence of piebaldism in presence of KIT haploinsufficiency. Am J Med Genet A 167A(1):231-237.