Skeletal Dysplasia_Fetal

Gene: NSDHL

Green List (high evidence)

Brain abnormalities.

Created: 2 Mar 2022, 10:25 p.m. | Last Modified: 2 Mar 2022, 10:25 p.m.

Panel Version: 0.4642

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
CK syndrome , MIM#300831

I don't know

First described in 7 males from a five-generation family, 1-bp duplication p.(Lys232del) reported by Tarpey et al. (2009). PMID:19377476.

Second affected family, p.(Arg367SerFs*33) reported by Tarpey et al. (2009) and McLarren et al. (2010) (PMID:19842190; 21129721). Functional studies showed that both mutations in these families result in partial loss of the function of the NSDHL protein and cause a distinct phenotype characterized by intellectual disability, seizures, microcephaly, cerebral cortical malformations, minor facial anomalies, and thin body habitus.

Third described in five- generation family (missense -p.Gly152Asp) with affected males manifesting clinical features of CK syndrome. (https://doi.org/10.1002/ajmg.a.36999) Clinical feature described in the paper similar to CK syndrome however, no mention of cortical malformation, pachygyria, polymicrogyria, features mentioned in OMIM. But one affected male has a CT scan showing atrophic changes in the brain, internal hydrocephalus, and possible subependymal gray matter heterotopia. NB: Therefore, unsure if this is the third family hence leaving as Amber.

Created: 26 Aug 2020, 1:27 a.m. | Last Modified: 26 Aug 2020, 1:27 a.m.

Panel Version: 0.97

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
CK syndrome 300831

Publications

• 19377476
• 19842190
• 21129721

Green List (high evidence)

3 multi generational families reported. All affected males had ID.

Created: 20 Jul 2020, 6:50 a.m. | Last Modified: 20 Jul 2020, 6:50 a.m.

Panel Version: 0.2776

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
CK syndrome (MIM#300831)

Publications

• 21129721
• 15689440
• 25900314