A Boy with Sandestig-Stefanova Syndrome and Genital Abnormalities

Abstract

<b><i>Introduction:</i></b> Sandestig-Stefanova syndrome is an autosomal recessive developmental syndrome characterized by microcephaly, trigonocephaly, congenital cataracts, microphthalmia, facial findings, camptodactyly, periventricular white matter loss, thin corpus callosum, delayed myelination, and poor prognosis. This syndrome is caused by biallelic loss-of-function mutations in the <i>NUP188</i> gene. <b><i>Case Presentation:</i></b> In the physical examination of our patient, whose mother and father were third-degree relatives, hypotonia, bilateral congenital cataracts, ambiguous genitalia, hypospadias, undescended testis, and facial dysmorphic findings (hypertelorism, high palate, micrognathia, microphthalmia, low-set ears) were detected. <b><i>Discussion:</i></b> In our patient, a homozygous c.1087C>T (p.Gln363Ter) variant was detected in exon 11 of the <i>NUP188</i> (NM_015354.3) gene. The mother and father were found to be heterozygous carriers of this variant. All patients with the diagnosis of Sandestig-Stevanova syndrome reported in the literature are female. Our patient is the first male patient reported with this syndrome. In addition, immunodeficiency, congenital hypothyroidism, biotinidase deficiency, undescended testis, hypospadias, and ambiguous genitalia are defined for the first time in this syndrome. Our patient is the first case of Sandestig-Stefanova syndrome reported from Turkey. In this study, Sandestig-Stefanova syndrome with a novel pathogenic <i>NUP188</i> gene variant is presented.

From the sideline: Tissue‐specific nucleoporin function in health and disease, an update

“…A recently defined developmental disorder termed Sandestig-Stefanova syndrome (SANDSTEF; MIM 618804) is based upon homozygous and compound heterozygous mutations in NUP188 (Fig. 5; Table 1; [104][105][106]). Patients had pre-and postnatal microcephaly and otherwise strikingly similar clinical features, including premature fusion of the skull (trigonocephaly), vision impairments, facial features, bent fingers (camptodactyly) and rocker-bottom feet, as well as heart and brain anomalies.…”

“…Patients had pre-and postnatal microcephaly and otherwise strikingly similar clinical features, including premature fusion of the skull (trigonocephaly), vision impairments, facial features, bent fingers (camptodactyly) and rocker-bottom feet, as well as heart and brain anomalies. Affected children were small at birth and early (infection-associated) respiratory failure led to demise in infancy or early childhood [104][105][106]. The NUP188 protein was undetectable in patient-derived fibroblasts and real-time PCR suggested that the mutant NUP188 alleles are targeted by nonsense-mediated decay.…”