5-α-Reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, a potent androgen responsible for male sexual development during the fetal period and later during puberty. Its deficiency causes an autosomal recessive disorder of sex development characterized by a wide range of under-virilization of external genitalia in patients with a 46,XY karyotype. Mutations in the SRD5A2 gene cause 5-α-Reductase deficiency; although it is an infrequent disorder, it has been reported worldwide, with mutational heterogeneity. Furthermore, it has been proposed that there is no genotype-phenotype correlation, even in patients carrying the same mutation. The aim of this review was to perform an extensive search in various databases and to select those articles with a comprehensive genotype and phenotype description of the patients, classifying their phenotypes using the external masculinization score (EMS). Thus, it was possible to objectively compare the eventual genotypephenotype correlation between them. The analysis showed that for most of the studied mutations no correlation can be established, although the specific location of the mutation in the protein has an effect on the severity of the phenotype. Nevertheless, even in patients carrying the same homozygous mutation, a variable phenotype was observed, suggesting that additional genetic factors might be influencing it. Due to the clinical variability of the disorder, an accurate diagnosis and adequate medical management might be difficult to carry out, as is highlighted in the review.

Supernumerary teeth represent a common human dental anomaly, defined as presence of extra teeth-more than the normal number foreseen in primary or permanent dentition. The prevalence has been reported between 0.2 to 3%, and is more frequent in males than females. The etiology is heterogeneous, highly variable and most of the cases are idiopathic. However, the presence of multiple impacted or erupted supernumerary teeth is rare and associated with some genetic syndromes: cleidocranial displasia, familial adenomatous polyposis, trichorhinophalangeal syndrome type I, Rubinstein-Taybi syndrome, Nance-Horan syndrome, Opitz G/BBB syndrome, oculofaciocardiodental syndrome and Robinow syndrome (autosomal dominant). The supernumerary teeth should be considered in order to possibly diagnose these entities with the aim of offering an interdisciplinary management and treatment, as well as offer adequate family genetic counseling.

Schmid-type metaphyseal chondrodysplasia (MIM 156500) is an uncommon autosomal dominant skeletal dysplasia caused by heterozygous mutations in the COL10A1 gene (MIM 120110) encoding the α1(X) chains of type X collagen. We report an 8-year-old girl with waddling gait, short stature, mild dorsal scoliosis, coxa vara, short lower limbs, bowing of the femurs, genu varum, and metaphyseal fraying and splaying, who is a carrier of a novel heterozygous 2-bp (c.1894_1895dupTA; p.Leu633Thrfs*45) duplication in exon 3 of the COL10A1 gene.

The Beckwith-Wiedemann syndrome is the most common genetic entity in overgrowth, with an approximate incidence of 1 in 10 00013 700births. Its broad clinical spectrum includes pre- and postnatal macrosomia, macroglossia, pinna abnormalities, abdominal wall defects, visceromegaly, and hyperinsulinemic hypoglycemia. This syndrome predisposes to childhood cancer and is caused by diverse genetic and/or epigenetic disorders that usually affect the regulation of genes imprinted on chromosome 11p15.5. The knowledge of (epi) genotype-phenotype correlations has prompted recommendations to propose different health care strategies, including tumor surveillance protocols based on molecular classification, aimed at standardizing clinical practice. The objective of this article is to describe the current status of the Beckwith-Wiedemann syndrome, a model of genomic imprinting.

Background: Craniosynostosis is described as the premature fusion of cranial sutures that belongs to a group of alterations which produce an abnormal phenotype. Case report: Two unrelated female patients with clinical findings of Apert syndrome-characterized by acrocephaly, prominent frontal region, flat occiput, ocular proptosis, hypertelorism, down-slanted palpebral fissures, midfacial hypoplasia, high-arched or cleft palate, short neck, cardiac anomalies and symmetrical syndactyly of the hands and feet-are present. In both patients, a heterozygous missense mutation (c.755C>G, p.Ser252Trp) in the FGFR2 gene was identified. Conclusions: Two cases of Apert syndrome are described. It is important to recognize this uncommon entity through clinical findings, highlight interdisciplinary medical evaluation, and provide timely genetic counseling for the family.