Multisystem Involvement in a Patient with a PTCH1 Mutation: Clinical and Imaging Findings.

In this article, we report on a Brazilian female patient born to consanguineous parents and presenting with alobar holoprosencephaly, severe eye involvement, and unusual skin hyperpigmented lesions. She was found to have a mutation (c.2240T > C; p.Val751Gly) in exon 15 of the PTCH1 gene. Mutations in this gene are associated with the nevoid basal cell carcinoma syndrome (NBCCS, OMIM 109400) and, in other instances, with holoprosencephaly (holoprosencephaly-7, OMIM 610828). Severe eye involvement ranging from orbital coloboma to microphthalmia has been seldom reported in patients with NBCCS with PTCH1 mutations. To our knowledge, this is the first report of an individual with central nervous system, skin, and eye manifestations due to a PTCH1 mutation. Mechanisms involved in these multisystem manifestations are discussed.

Clinical and genetic study on 356 Brazilian patients with a distinct phenotype of cleft lip and palate without alveolar ridge involvement.

Oral clefts include cleft lip (CL), cleft lip with cleft palate (CLP) and cleft palate (CP), with wide variations in clinical presentation and degree of severity. We described a sample of individuals with CL and CP without alveolar arch involvement (CL + CP) to verify if the characteristics of this group are distinct from those with CL with or without CP (CL/P) described in literature. The sample was composed of 356 patients with CL + CP, registered at HRCA-USP, Bauru-SP-Brazil. The following characteristics were investigated: sex ratio, parental age at the time of conception, parental consanguinity, familial recurrence, laterality of the cleft and associated anomalies. A subgroup of 30 individuals with microforms of CL and CP were taken from the sample and compared with the remaining cases. Statistical differences were found between this CL + CP sample and the literature data for groups with CL/P regarding laterality, sex ratio, consanguinity, familial recurrence, and the presence of associated anomalies. The microform sample showed a statistical difference in paternal age. In most evaluated aspects, this sample presents similar characteristics to the consulted literature data for CL/P; as do the group of microform cleft cases when compared with the remaining CL + CP sample in this study. Microforms of cleft can represent a target group for investigation into the embryogenetic mechanisms of oral clefts and their phenotypic variability.

Richieri-Costa-Pereira syndrome: a unique acrofacial dysostosis type. An overview of the Brazilian cases.

We reported on 16 new Brazilian patients and review findings in 12 previously reported cases (25 apparently unrelated Brazilian families) from Hospital of Rehabilitation of Craniofacial Anomalies, presenting with Richieri-Costa-Pereira syndrome. All patients display a unique pattern of anomalies consisting of microstomia, micrognathia, abnormal fusion of mandible, cleft palate/Robin sequence, absence of central lower incisors, minor ears anomalies, hypoplastic first ray, abnormal tibiae, hypoplastic halluces, and clubfeet. Learning disability was also a common finding. The sex-ratio showed deviation toward to female (1.8F:1M). Recurrence in sibs was observed in nine instances and consanguinity in 11, supporting the hypothesis of autosomal recessive inheritance. Nineteen of the 25 families lived in São Paulo State, seven of them (10 affected individuals) from an isolated region named "Vale do Ribeira." The geographic barrier of this region associated with the high incidence of the consanguineous matting suggested that this condition is caused by a rare mutation with a founder effect. With the exception of one patient in France, all known cases are of Brazilian origin. The causative gene of this rare syndrome remains unknown.