Dermatological findings in Rubinstein-Taybi Syndrome.

Rubinstein-Taybi Syndrome is a rare congenital multisystem syndrome inherited in an autosomal dominant pattern caused by mutations in CREBBP and EP300 genes in approximately 60% and 10% respectively. These genes encode two highly evolutionarily conserved, ubiquitously expressed, and homologous lysine-acetyltransferases, that are involved in number of basic cellular activities, such as DNA repair, cell proliferation, growth, differentiation, apoptosis of cells, and tumor suppression. It is mainly characterized by global developmental delay, moderate to severe intellectual disability, postnatal retardation, microcephaly, skeletal anomalies including broad/short, angled thumbs and/or large first toes, short stature, and dysmorphic facial features. There is an increased risk to develop tumors mainly meningiomas and pilomatrixomas, without a clear genotype-phenotype correlation. Although not considered as characteristic manifestations, numerous cutaneous anomalies have also been reported in patients with this entity. Both susceptibility to the formation of keloids and pilomatricomas are the most often associated cutaneous features. In this review, we discuss the genetics, diagnosis, and clinical features in Rubinstein-Taybi Syndrome with a review of the major dermatological manifestations.

A Severe Case of Spondylometaphyseal Dysplasia Algerian Type with Two Mutations in COL2A1.

Spondylometaphyseal dysplasia Algerian type (MIM no.: 184253) is an uncommon autosomal dominant skeletal dysplasia caused by heterozygous mutations in the COL2A1 gene (MIM no.: 120140). In this case based review, we reported a 5-year-old boy with short stature, severe dorsolumbar scoliosis, lumbar hyperlordosis, short trunk, and severe genu valgum . Radiological examination showed platyspondyly, irregular metaphyseal radiolucencies intermingled with radiodensities, and corner fractures. The patient has a c.3275G > A; p.Gly1092Asp mutation in exon 47 of the COL2A1 gene and a variant of unknown significance in c.1366-13C > A in intron 21. This latter sequence variant could partially or completely disrupt the natural splice acceptor site of intron 21/exon 22 in the COL2A1 gene leading to a potential modification of the phenotypic severity.

Clinical and Genetic Aspects of Phelan-McDermid Syndrome: An Interdisciplinary Approach to Management.

Phelan-McDermid syndrome (PMS) is a rare, heterogeneous, and complex neurodevelopmental disorder. It is generally caused by a heterozygous microdeletion of contiguous genes located in the distal portion of the long arm of chromosome 22, including the SHANK3 gene. Sequence variants of SHANK3, including frameshift, nonsense mutations, small indels and splice site mutations also result in PMS. Furthermore, haploinsufficiency in SHANK3 has been suggested as the main cause of PMS. SHANK3 is also associated with intellectual disability, autism spectrum disorder and schizophrenia. The phenotype of PMS is variable, and lacks a distinctive phenotypic characteristic, so the clinical diagnosis should be confirmed by genetic analysis. PMS is a multi-system disorder, and clinical care must encompass various specialties and therapists. The role of risperidone, intranasal insulin, insulin growth factor 1, and oxytocin as potential therapeutic options in PMS will be discussed in this review. The diagnosis of PMS is important to provide an appropriate clinical evaluation, treatment, and genetic counseling.