Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.

Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.

Restorations Versus Stainless Steel Crowns in Primary Molars: A Retrospective Split-Mouth Study.

Purpose: The purpose of this study was to evaluate the treatment outcomes of multisurface caries in primary molars treated with intracoronal restorations versus stainless steel crowns (SSCs) through a retrospective split-mouth study. Methods: Dental records were screened for patients who had treatment of one primary molar with a multisurface restoration and one primary molar with an SSC. Teeth were followed until a loss to follow-up, exfoliation, or failure. Results: A total of 988 primary molars were evaluated, with a mean follow-up time of 22 months. The survival probabilities for: SSCs were 95.5 percent at one year of service and 92.8 percent at two years of service; and for intracoronal restorations were 92.0 percent at one year of service and 80.0 percent at two years of service. Overall survival analysis showed SSCs to be significantly more successful than restorations (P<0.001), particularly in children treated at ages four years and younger (P<0.001). No statistically significant difference (P=0.10) was found for children treated at ages five years and older. Conclusions: Stainless steel crowns have a higher survival probability versus restorations for multisurface caries. In children ages four years and younger, more aggressive treatment of multi-surface caries with SSCs should be considered, as conservative treatment leads to an increased need for retreatment.

Nonimmune hydrops fetalis: identifying the underlying genetic etiology.

PURPOSE: Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes. METHODS: Retrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal-Maternal Consortium sites. Singleton pregnancies with prenatally diagnosed NIHF were included, and cases with maternal alloimmunization were excluded. Cases were categorized as being of confirmed, suspected, or unknown etiology. RESULTS: Sixty-five NIHF cases were identified. Forty-six percent (30/65) remained of unknown etiology, while 9.2% (6/65) had a suspected etiology and 44.6% (29/65) were of confirmed etiology. Among confirmed cases, 11 resulted from aneuploidy; 7 from fetal structural anomalies; 2 each from fetal arrhythmia, Noonan syndrome, and generalized lymphatic dysplasia; and 1 each from arthrogryposis, parvovirus, neonatal alloimmune thrombocytopenia, fetal goiter, and Kasabach-Merritt syndrome. CONCLUSION: In this contemporary, multicenter study, the cause of prenatally diagnosed NIHF was confirmed in only 44% of cases, and a genetic etiology was found in only 25% of those that received standard of care genetic testing.

Phenotypic variation in trismus-pseudocamptodactyly syndrome caused by a recurrent MYH8 mutation.

We report a 20-year-old man with trismus-pseudocamptodactyly (TPS) syndrome who was found to have the same MYH8 mutation, p.R674Q, described in previous families with TPS syndrome and in one family with a Carney complex variant, trismus and pseudocamptodactyly. This patient had facial asymmetry, ptosis and downslanting palpebral fissures and multiple joint involvement, with bilateral hip dysplasia, reduced elbow supination, vertical tali and talipes in addition to the classical findings of trismus and pseudocamptodactyly. These findings broaden the phenotype associated with p.R674Q mutations and support the use of MYH8 testing in patients with a clinical diagnosis of TPS syndrome.