Accelerating matchmaking of novel dysmorphology syndromes through clinical and genomic characterization of a large cohort.

PURPOSE: Dysmorphology syndromes are among the most common referrals to clinical genetics specialists. Inability to match the dysmorphology pattern to a known syndrome can pose a major diagnostic challenge. With an aim to accelerate the establishment of new syndromes and their genetic etiology, we describe our experience with multiplex consanguineous families that appeared to represent novel autosomal recessive dysmorphology syndromes at the time of evaluation. METHODS: Combined autozygome/exome analysis of multiplex consanguineous families with apparently novel dysmorphology syndromes. RESULTS: Consistent with the apparent novelty of the phenotypes, our analysis revealed a strong candidate variant in genes that were novel at the time of the analysis in the majority of cases, and 10 of these genes are published here for the first time as novel candidates (CDK9, NEK9, ZNF668, TTC28, MBL2, CADPS, CACNA1H, HYAL2, CTU2, and C3ORF17). A significant minority of the phenotypes (6/31, 19%), however, were caused by genes known to cause Mendelian phenotypes, thus expanding the phenotypic spectrum of the diseases linked to these genes. The conspicuous inheritance pattern and the highly specific phenotypes appear to have contributed to the high yield (90%) of plausible molecular diagnoses in our study cohort. CONCLUSION: Reporting detailed clinical and genomic analysis of a large series of apparently novel dysmorphology syndromes will likely lead to a trend to accelerate the establishment of novel syndromes and their underlying genes through open exchange of data for the benefit of patients, their families, health-care providers, and the research community.Genet Med 18 7, 686-695.

Heterotopic respiratory mucosa in the scalp overlying abnormal bony island in the skull linked to maternal misoprostol use, literature review and surgical experience.

BACKGROUND: Congenital scalp lesions rarely occur in children. These lesions are usually noticed at birth and mostly comprise skin and bone tissue loss in the form of acutis aplasia congenita. The management of these lesions is highly dependent on their location and the affected underlying structures. CASE REPORT: We report the case of a baby girl who was referred to us after a normal full-term delivery and who had an area of an abnormal overgrowth of skin (skin tag) on the vertex of the scalp, with an area of surrounding alopecia. She was otherwise healthy with no noted congenital anomalies. Apart from a prenatal history of attempted abortion using misoprostol, she had no significant history or congenital anomalies. She underwent a CT scan and an MRI. She also underwent an operation to excise the overgrowth and to address the underlying bone tissue anomaly. Histopathology showed respiratory mucosa heterotopia. We report this unusual case that suggests the need for an algorithm to manage such cases, as well as the need to investigate the possibility of misoprostol teratogenicity and a probable link to heterotopia. CONCLUSION: Congenital skin lesions on the scalp should be approached in a multidisciplinary manner to guide their treatment.