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Our aim was to characterize the phenotype and genotype of individuals with Noonan syndrome in Colombia. There are published cohorts of Noonan individuals from several countries in Latin America including Brazil, Chile, and Argentina, but none from Colombia. We described 26 individuals with NS from a single large referral center in the South West of Colombia using an established database in the genetics department and hospital records search using ICD-10 codes. All patients included in this study were evaluated by a medical geneticist and have molecular confirmation of NS diagnosis. The median age at referral was 3.5 years (range, 0-39), and at molecular diagnosis was 5 years (range, 0-40). Patients mostly originated from the southwest region of Colombia (19/26, 73%). Pathogenic variants in PTPN11 are the most common cause of NS in Colombian individuals followed by SHOC2 and SOS1 variants. The prevalence of cardiomyopathy was low in this population compared to other populations. Further research is needed with a larger sample size and including different regions of Colombia to correlate our findings. This study provides new information about time to diagnosis of NS in Colombia, genotypes, and provides important information to help develop guidelines for diagnosis and management of this disease in the region., (© 2020 Wiley Periodicals LLC.)

Purpose: To characterize the pediatric population with inborn errors of immunity (IEI) that was treated with hematopoietic stem cell transplantation (HSCT) in three reference centers in Colombia. What have been the characteristics and outcomes of hematopoietic stem cell transplantation in pediatric patients with inborn errors of immunity in three reference care centers in Colombia between 2007 and 2018?, Methods: We conducted an observational, retrospective cohort study in children with a diagnosis of IEI who underwent HSCT between 2007 and 2018., Results: Forty-seven patients were identified, and 5 were re-transplanted. Sixty-eight percent were male. The median age at diagnosis was 0.6 years, and for HSCT was 1.4 years. The most common diseases were chronic granulomatous disease (38%) followed by severe combined immune deficiencies (19%) and hemophagocytic lymphohistiocytosis (15%). Cord blood donors were the most used source of HSCT (44%). T cell-replete grafts from haploidentical donors using post-transplantation cyclophosphamide represent 37% of the cohort. All patients received conditioning, 62% with a non-myeloablative regimen. Calcineurin inhibitors were the main graft-versus-host disease prophylaxis (63.8%). Acute graft-versus-host disease developed in 35% of the total patients. The most frequent post-transplant infections were viral and fungal infections. The 1-year overall survival rates for the patients who received HSCT from identical, haploidentical, and cord sources were 80%, 72%, and 63%, respectively. The 5-year overall survival was 63%., Conclusions: HSCT is a curative treatment option for some IEI and can be performed with any donor type. Early and timely treatment in referral centers can improve survival.

Background: Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, comprises a variable phenotype with the most common features including microtia and mandibular hypoplasia on one or both sides, in addition to lateral oral clefts, epibulbar dermoids, cardiac, vertebral, and renal abnormalities. The etiology of CFM is largely unknown. The MYT1 gene has been reported as a candidate based in mutations found in three unrelated individuals. Additional patients with mutations in this gene are required to establish its causality. We present two individuals with CFM that have rare variants in MYT1 contributing to better understand the genotype and phenotype associated with mutations in this gene., Methods/results: We conducted genetic analysis using whole-exome and -genome sequencing in 128 trios with CFM. Two novel MYT1 mutations were identified in two participants. Sanger sequencing was used to confirm these mutations., Conclusion: We identified two additional individuals with CFM who carry rare variants in MYT1, further supporting the presumptive role of this gene in the CFM spectrum., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

South America comprises of heterogeneous topographies, populations, and health care systems. Therefore, it is not surprising to see differences among the countries regarding expertise, education, and practices of ophthalmic genetics for patients with rare eye diseases. Nevertheless, common challenges such as limited genetics training in medical schools and among ophthalmologists, scarcity of diagnostic tools for phenotyping, and expensive genetic testing not covered by the public healthcare systems, are seen in all of them. Here, we provide a detailed report of the current status of ophthalmic genetics, described by the personal views of local ophthalmologists from Brazil, Colombia, Argentina, and Chile. By reporting our strengths and weaknesses as a region, we intend to highlight the need for guidelines on how to manage these patients aligned with public health policies. Our region contributes to research worldwide, with thousands of well diagnosed patients from a number of unique and genetically diverse populations. The constant expansion of ophthalmic genetics and molecular diagnostics requires us to join forces to collaborate across South America and with other countries to improve access to next-generation diagnostics and ultimately improve patient care., (© 2020 Wiley Periodicals LLC.)

Background: Multiple primary malignant neoplasms are not frequent but are increasing in incidence. Some of them are associated with genetic syndromes such as von Hippel-Lindau syndrome and Li-Fraumeni syndrome. Dedifferentiated liposarcoma is one of the rarest soft tissue tumors, and clear cell renal carcinoma is the most frequent kidney cancer. The concomitant presence of these tumors is extremely rare; however, some cases have been reported, none of them presenting with liposarcoma of the limbs. We report an interesting case of a patient with synchronous multiple primary tumors presenting with a very rare liposarcoma associated with renal cell carcinoma (a very rare association). A review of the literature and a collection of similar cases published previously are also provided., Case Presentation: We report a case of a 62-year-old Hispanic man who presented to our institution with a left thigh mass compatible with dedifferentiated liposarcoma synchronous with metastatic clear cell renal carcinoma. Multiple treatment lines were provided with no response, with a further metastatic transformation. Genetic analysis by liquid biopsy showed some mutations that were not susceptible to targeted therapy. At the time of this report, the patient is undergoing palliative care because his nonresponsive metastatic disease persists., Conclusions: We present the first reported case of clear cell renal carcinoma synchronous with dedifferentiated liposarcoma of a limb. The association between renal cell carcinoma and dedifferentiated liposarcoma is unusual, and there are few reports of this presentation in the literature. More research about these tumors along with genetic tests needs to be performed to seek a better understanding of the fundamental basis of this rare association.

Introduction: In Colombia, the genetic background of the populations was shaped by different levels of admixture between Natives, European, and Africans. Approximately 35.363 patients have diagnosed chronic kidney disease and according to population studies, 10.4% of these patients are Afro-descendant. We aim to assess the frequency of APOL1 variants G1 and G2 in Afro-descendant patients with ESRD treated at la Fundacion Valle del Lili University Hospital in Cali, Colombia., Methods: This is an observational cross-sectional study. Afro-descendant patients with ESRD in waitlist or recipients of kidney transplant were evaluated. Clinical data were collected from the electronic medical records. Genotyping was carried out by amplification of the exon 7 of the APOL1 gene. For the identification of risk genotypes, the bioinformatics tool BLAST was used., Results: We enrolled 102 participants. The frequency of APOL1 risk variants was 67.2%, in which 24.5% ( n  = 25) were G1 heterozygous and 5.8% ( n  = 6) were G2 heterozygous and 37% of the patients had high-risk status with two alleles in homozygous (G1/G1 = 21 and G2/G2 = 3) or compound heterozygote (G1/G2 = 14) form., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2019 Carlos E. Duran et al.)

3-Hydroxyisobutyryl-coenzyme A (CoA) hydrolase deficiency (HIBCHD; MIM: #250620) is a rare autosomal recessive inborn error of metabolism caused by a defect in the HIBCH enzyme, resulting in a deficiency of the conversion of 3-hydroxy-isobutyryl-CoA to 3-hydroxy-isobutyric acid, a critical step in valine catabolism. This neurodegenerative disease of infancy is associated with hypotonia, developmental delay, cerebral atrophy and lesions in the basal ganglia on magnetic resonance imaging (MRI). In this study, we describe two unrelated patients with infantile-onset progressive neurodegenerative disease and mutations in HIBCH identified using whole exome sequencing (WES). In Case 1, WES revealed a novel homozygous variant in the HIBCH gene: c.808A>G (p.Ser270Gly). In Case 2, a novel compound heterozygous mutation in the HIBCH gene is described: c.808A>G (p.Ser270Gly) and c.173A>G (p. Asn58Ser). Parent analysis revealed that c.808A>G (p.Ser270Gly) was inherited from the father and c.173A>G (p. Asn58Ser) from the mother. These novel mutations were predicted as a disease-causing mutation. Plasma acylcarnitine analysis was normal in both patients. Physical examination showed similar features, such as axial hypotonia and spastic hypertonia in the legs. The first patient presented with difficult-to-treat seizures, while the second patient has not yet experienced documented seizures. In conclusion, our findings would widen the mutation spectrum of HIBCH deficiency and the phenotypic spectrum of the disease. The potential genotype-phenotype correlation would be profitable for the correct diagnosis, treatment and integral management of patients with HIBCH deficiency.

Paragangliomas are tumors that originate from the extra-adrenal neural crest, the incidence of which during pregnancy is not more than two to eight cases per million people per year and are known to be highly morbid. The purpose of this report is to describe the experience and results obtained during management of a primigravida diagnosed with paraganglioma on week 21.2 and received both medical and surgical management with good maternal and perinatal outcomes. This case report evidences the importance of practicing interdisciplinary management of patients with clinical suspicion of paragangliomas or pheochromocytomas during pregnancy at high-complexity centers even in a medium-income country.

Ehlers-Danlos syndrome (EDS) is a group of clinically and genetically heterogeneous inherited connective tissue disorders, characterized by skin hyperextensibility, poor wound healing, joint hypermobility and tissue friability. Since 1997 a new spectrum of novel rare EDS-variants has been described, among which is included the EDS kyphoscoliotic type, characterized by severe muscular hypotonia at birth, severe progressive kyphoscoliosis, osteopenia, fragile eyeballs and vascular fragility. This EDS variant is caused by mutations in the PLOD1 gene; however, a rare recessive variant that compromises the FKBP14 gene has been reported, with additional clinical findings that includes gross motor developmental delay, myopathy, hearing impairment and a normal ratio of lysyl pyridinoline to hydroxylysyl pyridinoline in urine. We report the first Colombian patient with a FKBP14 c.362dupC mutation, with clinical features that include generalized hypotonia, delayed gross motor milestones, hearing loss, early-onset progressive kyphoscoliosis, joint hypermobility and foot deformities., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Lysosomal acid lipase deficiency is a genetic disease with a low prevalence and high morbidity and mortality in children and adults. It is characterized by an alteration of lipid metabolism, which generates cholesterol and triglyceride esters deposits in the body. Its clinical presentation depends on enzymatic activity. This condition should be suspected in patients with lipid or liver alterations after ruling out other diagnoses. Currently, there is the option of using a recombinant enzyme, which can improve lipid and liver parameters, as well as disease progression. Establishing a timely diagnosis in order to initiate specific treatment early is imperative for the prevention of morbidity and mortality. The purpose of this work is to perform a review of the literature about lysosomal acid lipase deficiency and to guide about its pathophysiology, clinical manifestations, diagnosis and treatment., (Copyright: © 2019 SecretarÍa de Salud.)

Introduction: Microcephaly is characterized by a smaller than normal head circumference. Recently, Zika virus (ZV) has been associated with microcephaly., Objective: To describe the prevalence of microcephaly in Colombia taking as the baseline the information from the period before the Zika virus infection epidemics., Materials and Methods: We reviewed Medline, Scopus, Scielo, Lilacs and annual reports of congenital malformation monitoring systems across Latin America, among others sources, for articles published before April, 2015, reporting the prevalence of microcephaly in Colombia between 1982 and 2013., Results: We identified 32 non-duplicate articles; we selected 25 articles for revision of which 12 met the criteria for inclusion in the systematic review, including 2,808,308 births., Conclusions: The prevalence of microcephaly in Colombia from 1982 to 2013, before the introduction of ZV, ranged from 0.3 to 3.1 per 10,000 births, with an average of 1.8 (95% CI 1.7-1.8) per 10,000 births. These findings are important to determine if the prevalence after the introduction of the Zika virus infection registered significant changes.

BACKGROUND Lysosomal acid lipase deficiency is a rare genetic metabolic lipid storage disease, with a high morbidity, and mortality, in children and adults. It is characterized by a mutation in the LIPA gene that causes an alteration of lipid metabolism, resulting in deposits of cholesterol esters and triglycerides in organs such as the liver, blood vessels, and gastrointestinal tract. Lysosomal acid lipase deficiency is predominantly caused by the mutation c.894G>A, seen in approximately 50-70% of patients. Our objective is to report the first pediatric case of lysosomal acid lipase deficiency in a pediatric patient in Colombia. CASE REPORT The patient is a 14-year-old boy with isolated hepatomegaly since 6 years of age without a family history of dyslipidemia. In the pediatric control, laboratory exams revealed dyslipidemia, and a hepatic biopsy was performed, revealing severe fibrosis with septation and grade 3 microvesicular steatosis (>75%). He was referred to our center and was suspected to have lysosomal acid lipase deficiency. Enzymatic activity was measured, showing absent activity. Confirmatory diagnosis with genetic sequencing showed a pathological homozygous mutation of c.894G>A. CONCLUSIONS Lysosomal acid lipase deficiency can manifest as early- or late-onset, with variable and severe signs and symptoms. The late-onset form has a broad spectrum of manifestations with mild symptoms, leading to under-diagnosis, which increases the actual disease burden. Early diagnosis is essential to initiate enzyme replacement therapy, since the natural disease course can be changed. More studies should be conducted in Latin America to evaluate the prevalence of the disease.

Pathogenic variants in WAC are uncommon causes of developmental delay and neurobehavioral phenotypes. The clinical features associated with WAC haploinsufficiency include recognizable dysmorphic facial features that were recently delineated as DeSanto-Shinawi syndrome (DESSH; OMIM 616708). Additional clinical features include hypotonia, hearing and vision abnormalities, gastrointestinal problems, and behavioral difficulties. Here, we report a case of a 4-year-old Colombian male patient with typical dysmorphic facial features, developmental delay, hyperactivity, and recurrent respiratory infections. His immune workup revealed hypogammaglobulinemia, and clinical exome sequencing revealed a novel intronic variant in WAC (c.1437+1G>A). To the best of our knowledge, this is the first case of DESSH in South America, underlining the accumulating evidence of the significant role of WAC haploinsufficiency in neurobehavioral phenotypes. Although this report suggested the potential involvement of WAC in immune regulation, additional reports are required to confirm our observations.

Tuberous sclerosis complex (TSC) is a neurocutaneous autosomal dominant disorder that results from mutations within either the TSC1 gene or the TSC2 gene. Diagnosis is based on well-established clinical criteria or genetic criteria. Clinical features are highly variable and could be developing over the life. We present a case of TSC with a molecular test that identified a novel variant in TSC2 gene. It is a sporadic missense mutation which has not been previously reported in the literature. It is caused by premature termination of protein translation and results in the production of truncated and non-functional proteins. This mutation is considered as a pathogenic variant and allows to broaden the spectrum of variants of TSC2 gene as a cause of TSC., (Sociedad Argentina de Pediatría.)

Introduction: The data regarding birth defects at local levels in developing countries like Colombia are scarce., Objective: To describe the profile of congenital abnormalities in the province of Risaralda, Colombia., Materials and Methods: We included the information on infants with structural and functional abnormalities at birth between June, 2010, and December, 2013, from records of the Instituto Nacional de Salud, and compared it with those of children born in the same period in a local clinic participating in the Collaborative Study of Congenital Malformations. We analyzed the data using Stata 10®., Results: We found a prevalence of nine defects per 1,000 newborns from the total live births in Risaralda. The local clinic registered in the Collaborative Study of Congenital Malformations registered a prevalence of 34 defects per 1,000 births. Most frequent defects were heart defects, followed by cleft lip and palate, abdominal wall defects, skeletal dysplasia, hydrocephalus, polydactyly and Down syndrome., Conclusions: Having a baseline on the prevalence of congenital defects in Risaralda is very useful in the design of prevention policies oriented to decrease congenital defects incidence and severity. Inclusion of maternity hospitals in the Collaborative Study of Congenital Malformations strengthens national recording and reporting of birth defects.

Deletion on the short arm of chromosome 18 is an infrequent syndrome and it is characterized by the following features: mental retardation, growth retardation, craniofacial malformations such as large ears, microcephaly, and short neck. The phenotypical spectrum is a wide range of abnormalities including minor congenital abnormalities to holoprosencephaly. We present a case of a 10 year old girl who is found to have a deletion on the short arm of chromosome 18 (18p11.32-p11.21), by conventional cytogenetic analysis and comparative genomic hybridization., (Sociedad Argentina de Pediatría.)

Background: Pulmonary surfactant is a complex mixture of lipids and proteins. Mutations in surfactant protein-C, surfactant protein-D, and adenosine triphosphate-binding cassette subfamily A member 3 have been related to surfactant dysfunction and neonatal respiratory failure in full-term babies. Adenosine triphosphate-binding cassette subfamily A member 3 facilitates the transfer of lipids to lamellar bodies. We report the case of patient with a homozygous intronic ABCA3 mutation., Case Presentation: We describe a newborn full-term Colombian baby boy who was the son of non-consanguineous parents of mixed race ancestry (Mestizo), who was delivered with severe respiratory depression. Invasive treatment was unsuccessful and diagnosis was uncertain. Exons 4 and 5 of the SP-C gene showed heterozygous Thr138Asn polymorphism and homozygous Asn186Asn polymorphism respectively. At intron 25 at position -98 from exon 26 a homozygous C>T transition mutation was detected in ABCA3 gene., Conclusions: The clinical presentation and the histopathological findings of this case are consistent with a case of neonatal respiratory failure due to surfactant deficiency. Analysis of the five coding SP-C exons does not support surfactant deficiency. An analysis of the mutation IVS25-98 T was performed and a homozygous mutation responsible for our case's neonatal respiratory failure was detected. The findings suggest an autosomic recessive pattern of inheritance. Genetic counseling was provided and the relatives are now informed of the recurrence risks and treatment options.

The Langer-Giedion syndrome, also known as trichorhinophalangeal syndrome type II, is a hereditary multisystemic disease part of the group of contiguous gene deletion syndromes. The cause of this syndrome is a heterozygous deletion that involves the chromosomal region 8q23.3-q24.11 and mainly affects genes TRPS1, RAD21, and EXT1. This syndrome is characterized by the presence of multiple osteochondromas in limbs, hypertrichosis, and facial phenotype that includes sparse scalp hair, large laterally protruding ears, a long nose with a bulbous tip. We report the case of a Colombian patient with finding of an 8q23.1-q24.12 deletion by comparative genomic hybridization array technique and classical clinical findings, being the first case reported in Colombia., (Sociedad Argentina de Pediatría.)

Background: Genetic disorders are a major cause in the etiology of cases with intellectual disability; however, analysis by a conventional technique such as cytogenetic karyotyping only allows the detection of chromosomal alterations in approximately 9.5 % of cases. The inclusion of new technologies such as high resolution microarray analysis has allowed the study of alterations in chromosomal segments that are less than 5 Mb in length; this has led to an increase in the diagnosis of these patients of up to 25 %., Case Presentation: We report the first case of an 8-year-old Colombian girl of mixed race ancestry (Mestizo), with clinical features that include: delayed psychomotor and language development, intellectual disability, upward slanting palpebral fissures, divergent strabismus, low-set and rotated ears, tall and broad nasal bridge, flat philtrum, bifid uvula, posterior cleft palate, increased anteroposterior diameter of her chest, congenital heart defect type interventricular communication, scoliosis, and umbilical hernia. Genetic analysis was performed using comparative genomic hybridization array, which evidenced the deletion of a region of approximately 3.608 Mb on chromosome 21q22.3, and a duplication of 12.326 Mb on chromosome 7q35q36.3, these alterations affect approximately 112 and 186 genes, respectively., Conclusions: To date, this is the first report of an associated terminal deletion of 21q and 7q duplication in a patient with delayed psychomotor development and intellectual disability. We consider that future implementation of exome and RNA sequencing techniques, and analysis of their proteomic expression in a clinical context could lead to better analysis and interpretation of the genotype-phenotype correlation in cases similar to that described.

Objective To identify clinical guidelines for the treatment of cleft lip and / or palate in children under one year of age, published in Colombia and internationally. Method A search was conducted in three databases: PubMed, Lilacs and Scielo with the terms "guideline cleft lip and palate", "protocols cleft lip and palate", "guía clínica labio paladar fisurado", "guía de manejo labio paladar fisurado" and "guía labio paladar hendido". In addition to this, we consulted the websites of all pediatric hospitals in Colombia. Results 190 papers were found, of which 96 were not related to the population or focused on treatment, 84 were disciplinary, 8 interdisciplinary and only two were clinical guidelines. Conclusions There are few published guidelines and there is a lack of unified criteria. This gives rise to numerous forms of intervention and the creation of interdisciplinary teams. Therefore, there is a need to reach a consensus regarding the therapeutic approach in order to create treatment protocols based on evidence with quality standards.

Background: It is estimated that 2 to 35 of newborns present a congenital malformation. Some publications suggest that vascular disruption birth defects are not associated with chromosomal alterations detected by conventional karyotype., Objective: to determine the frequency of chromosomal alterations detected by high resolution G banded karyotype in patients with vascular disruption birth defects in a Colombian population (South America)., Material and Method: transversal study. Population: a sample of patients identified by an epidemiological surveillance system of congenital malformations in a reference hospital in Cali, Colombia., Results: 41 cases of vascular disruption birth defects were identified during a 36 month period; in a descending order those were: transverse reduction defects, hydranencephaly and gastroschisis. Two expert cytogenetists performed independent evaluation of the genetic material of the patients, and no chromosomal alterations detectable by G banded karyotype were identified., Conclusions: It is recommended that genetic counseling in cases of defects by vascular disruption is carried out taking into account the empirical recurrence risks reported for each one the types of defects by vascular disruption and the use of karyotype should be limited to cases with other malformations or chromosomal abnormality suspected by phenotype.

Fibrodysplasia ossificans progressiva (FOP, MIM 135 100) is an uncommon genetic disease with a dominant autosomal germline transmission pattern; however, most cases are products of spontaneous individual mutations. It is a disabling condition that affects connective tissue, and it is distinguished by progressive heterotopic ossifications and congenital malformations of the great toes. The case of 2 brothers with progressive osseous deformation, along with ankylosis of the jaw, scoliosis and mental retardation, is presented. Blood samples were taken from each patient identifying in both of them a heterozygote mutation in exon 6 of the gene ACVR1 (c.617G>A p.Arg206His), which diagnoses the 'classic' form of FOP. The current medical treatment of this disease is early detection to avoid trauma and aggravating factors, prophylactic measures against infections and respiratory decline, symptomatic relief and physical therapy. There is currently no cure for the disease., (2015 BMJ Publishing Group Ltd.)

Introduction: Birth defects are morphologic alterations diagnosed prenatal or postnatally. Surveillance systems have been used to estimate the prevalence in high complexity care centers; however, the variation of the prevalence among different complexity care centers remains unknown., Objective: To compare the prevalence of birth defects among two different complexity care centers in Cali, Colombia., Materials and Methods: A descriptive hospital-based study following the methodology of the Latin American Collaborative Study of Congenital Malformations was conducted during 20 months in a medium complexity hospital and a high complexity hospital., Results: During the study period, 7,140 births were attended of which 225 had at least one birth defect. The prevalence of these was of 1.7% (IC95% 1.3-2.0) and 7.4% (IC95% 6.2-8.7) for the medium complexity hospital and the high complexity hospital, respectively. The highest frequencies for the high complexity care center were: ventricular septal defect, 10%; congenital hydronephrosis, 7%; abdominal wall defects, 6%, and hydrocephalus, 5%, while for the medium complexity were: polydactyly, 15%; preauricular skin tags, 8%; congenital talipes equino varus, 7%, and hemangioma, 6%., Conclusions: The prevalence of birth defects among different complexity care centers varies in quantity, type and severity of the anomaly diagnosed. The surveillance of birth defects is a useful tool for any level of care. It allows estimating more accurately the prevalence of the city, as well being a base for the planning and targeting of resources according to the prevalence of different congenital defects.

Down syndrome is the leading cause of inherited intellectual disability; it is characterized by mental retardation associated to physical growth delay and certain physical traits or features. It is caused by the presence of a third copy of chromosome 21, being this trisomy the most common chromosomal aneuploidy. Women with Down syndrome are less fertile, and pregnancy in these women is rare, although the information on exact statistics of reproduction in these patients is very limited, and they often have difficulties with miscarriage, premature birth, and difficult labor. We report the case of a preterm newborn with Down syndrome passed from her mother; this pregnancy was a result of sexual assault, which is an event that can and should be prevented in this population.

Mucopolysaccharidosis type VI or Maroteaux Lamy syndrome is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B, the clinical features include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism, with intelligence usually normal. We present evidence of the possible existence of Maroteaux Lamy syndrome in pre-Columbian pottery 2000 years ago, in the Colombo-Ecuadorian Pacific coast of the Tumaco-Tolita culture.

Introduction: Microcephalic osteodysplastic primordial dwarfism is a syndrome characterized by the presence of intrauterine growth restriction, post-natal growth deficiency and microcephaly. Microcephalic osteodysplastic primordial dwarfism type II is the most distinctive syndrome in this group of entities. Individuals affected by this disease present at an adult height of less than 100 cm, a post-pubertal head circumference of 40 cm or less, mild mental retardation, an outgoing personality and bone dysplasia., Case Presentation: We report the first case of a five-year-old Colombian boy of mixed race ancestry (mestizo), with clinical features of microcephaly, prominent and narrow nose, arched palate, amelogenesis imperfecta, short stature, tall and narrow pelvis, disproportionate shortening of fore-arms and legs, and mild coxa vara. Analysis of the PCNT gene by sequencing showed the presence of a nucleotide change in exon 10, c. 1468C>T, evidencing a new mutation not reported in the literature for microcephalic osteodysplastic primordial dwarfism., Conclusion: The new mutation identified in this case could be associated with the severity of the phenotypic expression of the disease, resulting in the extreme short stature of the patient. Further studies are required to reach an explanation that can justify such findings, and it is vital to emphasize the importance of detection and follow-up by the epidemiological surveillance groups in birth defects and rare diseases.

Craniofacial duplication or diprosopus is a very rare malformation that is present in approximately 0.4% of conjoined twins. Here is presented a case of craniofacial duplication in association with bilateral cleft lip/palate in both heads found in a ceramic representation from the early Chimú culture from Peru. A comparative analysis is made with a current case of a 28-week-old fetus with similar characteristics. After reviewing the medical literature on conjoined twins, very few reports of facial cleft in both twins were found, with no reports at all of bilateral cleft lip/palate. This ceramic crock is considered one of the first representations suggestive of craniofacial duplication, and probably the first reporting it in association with facial cleft.

Huntington's disease is a neurodegenerative disease that is clinically manifested as mood and personality changes, loss of cognitive functions and choreiform movements. The pattern of inheritance is autosomic dominant. It is due to the gradual expansion of a cytosine, adenine, guanine trinucleotide in a gene that codifies the protein Huntington. The molecular diagnosis must be performed to confirm the diagnosis. Genetic counseling must be carefully done due to the high suicide risk among these patients. We present the case of a fourteen-year-old male with a severe disease, poor social support and an unclear pattern of inheritance.

Mosaic trisomy 13 occurs when there is a percentage of trisomic cells for an entire chromosome 13, while the remaining percentage of cells is euploid. The prevalence of this syndrome ranges from 1 in 10 000 to 1 in 20 000 births. Complete, partial or mosaic forms of this disorder can occur. The phenotype of mosaic trisomy 13 patients varies widely. Patients with mosaic trisomy 13 usually have a longer survival and a less severe phenotype compared to patients with complete trisomy 13. Genetic counselling is difficult due to the wide variation among the clinical manifestations of these patients. There have been 49 cases of mosaic trisomy 13 reported in the literature. We report the case of a patient with mosaic trisomy 13, a sacral appendage and a cleft lip and palate.

We report the case of a newborn girl with a double trisomy, with a chromosome complement 48,XXX,+18, with Edwards syndrome phenotype (trisomy 18). The clinical feature included intrauterine growth retardation, dysmorphic facies, hand with overlapping fingers, ventricular septal defect, pulmonary stenosis and left clubfoot. A review of the literature and discussion of previously reported cases is made.

The ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome is a rare entity associated with mutations in the genes that express the protein p63. We present a case of a patient with right foot ectrodactyly associated with cleft lip and palate, without other evident anomalies. The patient has a positive familiar history for cleft lift and palate and mortality during the perinatal period. The management of each case must be specific and multidisciplinary.

Introduction: Achondroplasia is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, genu varum, and trident hand. Although the etiology of this disease was reported in 1994, evidence of this disease in ancient populations has been found in populations of ancient Egypt (2500 BC) and it has been documented in ancient American populations., Objective: To analyze the presence of individuals with achondroplasia in the Mayan state society of Mexico and Guatemala, during the Classical (100- 950 AC ) and Post-Classical (950 - 1519 AC ) periods; likewise, in the hierarchical-chieftain society of Tumaco-la Tolita (300 BC - 600 AC ) from the Colombia-Ecuador Pacific coast, and the Moche state society (100 - 600 AC ) from the northern coast of Peru., Methods: Iconographic and clinical-morphological studies of some of the most important artistic representations of individuals of short stature in these three cultures., Conclusion: We present the hypothesis that the individuals with short stature were somehow associated with the political and religious power elite.

Isotretinoin is a retinoid that derivates from vitamin A. It is indicated for recalcitrant nodular acne treatment, but it has been classified as teratogenic. A wide spectrum of birth defects including craniofacial, heart and nervous system malformations have been described associated to prenatal exposure to this drug. We report the case of a newborn with a history of prenatal exposure to isotretinoin with craniofacial defects, including facial paralysis, right anotia, left microtia and complex heart disease. Key words: isotretinoin, congenital abnormalities, teratology.

The complex agnatia holoprosencephaly (CAH) is characterized by absence or severe hypoplasia of the mandible, abnormal position of the ears, microstomia and holoprosencephaly. A case of mother son aged 34, gravida 3, part 2, with multiplanar three-dimensional ultrasound diagnosis of holoprosencephaly and anatomical detail otocefalia, so diagnosis of CAH was made. A review of the literature and discuss the differential diagnosis.