Sotos syndrome is reported to occur in approximately 1/10,000–15,000 of births . It is characterized by certain facial features. Early teething, high arching palate, pointed chin, prominent jaw, plethoric face, frontoparietal balding and macrocephaly are among those features. Additionally, kyphosis or scoliosis can also be seen in those patients however, there is no report in the previous literature associating Sotos syndrome with an intraspinal lipoma and tethered spinal cord.
Kurotaki et al. reported the underlying genetic abnormality of the Sotos Syndrome as mutations of the NSD1 gene which acts as a co-repressor or a co-activator . NSD1 includes two nuclear receptor-interacting domains (NIDs). These ligand-binding area perform on part of nuclear receptors which characteristics of both co-activators and co-repressors. The chromosome 5q35.2 gene on the NSD1 gene likewise plays a role in these two tasks. The NSD1 gene makes directives for making a protein that functions as a histone methyltransferase. Histones are structural proteins that bind to DNA (deoxyribonucleic acid) and Histone methyltransferases enzymes are modified. Members of the NSD family have a key role in controlling cell growth and differentiation for this subgroup of SET domain proteins which called nuclear receptor-binding proteins. The NSD1 enzyme controls the activity of normal growth and development of these genes. Abnormality in NSD1 protein leads to uncontrolled overgrowth [6, 7].NSD1 microdeletion deletes genetic material from the part of chromosome 5. So NSD1 gene mutations cause an abnormally small, nonfunctional enzyme. And then NSD1 enzyme disrupts the normal activity of genes involved in growth and development because NSD1 gene plays a role in the development of important hormones such as steroids and thyroids required for growth. In the light of current studies, the relationship of these genes specific to phenotype has not been explained yet. However, disruption of proper growth as a result of deletion defect in these genes may cause this dysmorphic phenotype in Sotos syndrome. At the same time, uncontrolled growth may cause phenotype properties as well as results such as spinal lipoma.
However, it is not known exactly how a shortage of this enzyme during development leads to overgrowth, mental retardation and the other signs and symptoms of Sotos syndrome. We thought that this uncontrolled growth may have triggered the spina bifida and the formation of intradural lipoma tethering the cord.
Tethered cord syndrome and fatty filum terminale are rare neurological conditions. Fatty filum terminale or benign lipoma continuous to the spinal cord like a lipomyelomeningocele, in which a lipoma extrudes from the spinal canal underneath the lining of the spinal cord that covered by normal skin. In some cases, it may be the result of improper growth of the neural tube during fetal development, which is closely linked to spina bifida. Although tethered cord syndrome is associated with other syndromes such as sacral agenesis, VACTAREL syndrome, multiple pterygium syndrome (MPS) and Escobar syndrome , there is no previous report on the association of tethered cord syndrome with the Sotos syndrome.
We found only one study about spinal malformations in the Sotos syndrome. Lim et al. reported 8 patients with Sotos syndrome who had spina bifida and other spinal anomalies . In their series, they report that all 8 patients had features of spina bifida. Although they do not clearly describe details of the spina bifida in their article we assumed that the described spina bifida was in a mild form of arcus fusion defects since they highlight that in none of their cases there were no thickened filum, tethered cord syndrome or dermal sinus tract requiring surgical intervention. So, we believe our case is the first one described in the literature that presents with Sotos syndrome and an additional tethered cord.
Sotos syndrome is a rare and complicated syndrome. Patients with this syndrome should be thoroughly evaluated for additional – surgery requiring – spinal pathologies.