Journal of Pediatric Genetics - Volume 2, issue 1

Authors: Nagy, Bálint

Article Type: Review Article

Abstract: The development of polymerase chain reaction revolutionized the molecular genetics and diagnostics. Technical improvements helped to make more specific and sensitive target determinations. Introduction of real-time polymerase chain reaction makes possible several applications in clinical genetics like detection of gene mutations, single nucleotide polymorphisms, deletions, measurement of gene expressions, micro ribonucleic acids, free nucleic acids and microbial genomes. Here I discuss a few examples for specific applications in prenatal clinical genetic practice. These are the detection of microbial genomes, deletions, trisomies, mutations, single nucleotide polymorphisms and free nucleic acids.

Keywords: Real-time PCR, microbial genome, cystic fibrosis, free nucleic acids

DOI: 10.3233/PGE-13042

Citation: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 1-8, 2013

Authors: Hartsfield, James K. | Morford, Lorri A. | Otero, Liliana M. | Fardo, David W.

Article Type: Review Article

Abstract: Just as pediatricians and endocrinologists are interested in understanding statural growth patterns and the prediction of adult height, pediatric dentists, orthodontists, and oral/maxillofacial surgeons need to be knowledgeable about a patient’s facial growth patterns to effectively treat them. Some variations in facial growth have been clinically associated with a poor esthetic self-image, malocclusion formation and the development of physical and/or functional deformity. To understand how different genetic factors influence growth and development patterns, scientists and clinicians study developmental sequences, malformations and syndromes. While understanding this general information can be clinically valuable when making treatment decisions for an individual and their …family, the greatest contribution of genetics in clinical practice may be in the form of personalized or “precision” medicine in the general population. Precision medicine takes into account knowing a portion or all of a patient’s specific DNA code to estimate how their genetic makeup will influence growth and development patterns. Ultimately, the identification of key genetic variations at the level of the individual patient can improve growth predictions for that patient and may be indicative of how well they will respond to specific forms of treatment. Show more

Keywords: Facial growth, oral facial genetics, genetics, malocclusion

DOI: 10.3233/PGE-13041

Citation: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 9-20, 2013

Authors: Ahmadu, Baba Usman | Yakubu, Mava | Abdullahi, Ibrahim Bello | Pwavimbo, Ambe Jose | Mahmud, Talba Aliyu | Clapton, Difirwiti Harry

Article Type: Research Article

Abstract: Known sex specific differences in fetal, neonatal morbidity and mortality have been documented. Sex differences also exist in birth-weight centile with males being larger than females at birth. However, these sex differences are not fully explored when studying passive measles immunity acquired by babies from their mothers. Moreover, the mechanisms that confer these sex differences are to a large extent unknown. Therefore, this study assessed sex of babies as a determinant of measles immunoglobulin G acquisition from their respective mothers. One hundred and seventy four newborn babies were enrolled in this study. Enzyme linked immunosorbent assay was used to measure …maternal measles antibodies (MMA) from sera collected from these babies at birth. Gestational age of the newborn babies was determined using the Nagele rule, ultrasound scan reports and the Dubowitz criteria. Sex and mean MMA of these babies was compared using the Student’s t test. Significant comparison existed between mean MMA and sex of post term babies (P = 0.000), such that post term males had higher levels of MMA than females. However, overall sex and mean MMA comparison of these babies was not significant (P = 0.977). There were more MMA in male post term babies relative to their female peers; however, overall sex comparison of MMA was not significant. Therefore, there is the need for further study. Show more

Keywords: Maternal measles antibodies, sex, newborn babies, teaching hospital, Nigeria

DOI: 10.3233/PGE-13043

Citation: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 21-24, 2013

Authors: Marano, Rachel M. | Mercurio, Laura | Kanter, Rebecca | Doyle, Richard | Abuelo, Dianne | Morrow, Eric M. | Shur, Natasha

Article Type: Research Article

Abstract: Array comparative genomic hybridization (aCGH) testing can diagnose chromosomal microdeletions and duplications too small to be detected by conventional cytogenetic techniques. We need to consider which patients are more likely to receive a diagnosis from aCGH testing versus patients that have lower likelihood and may benefit from broader genome wide scanning. We retrospectively reviewed charts of a population of 200 patients, 117 boys and 83 girls, who underwent aCGH testing in Genetics Clinic at Rhode Island hospital between 1 January/2008 and 31 December 2010. Data collected included sex, age at initial clinical presentation, aCGH result, history of seizures, autism, dysmorphic …features, global developmental delay/intellectual disability, hypotonia and failure to thrive. aCGH analysis revealed abnormal results in 34 (17%) and variants of unknown significance in 24 (12%). Patients with three or more clinical diagnoses had a 25.0% incidence of abnormal aCGH findings, while patients with two or fewer clinical diagnoses had a 12.5% incidence of abnormal aCGH findings. Currently, we provide families with a range of 10–30% of a diagnosis with aCGH testing. With increased clinical complexity, patients have an increased probability of having an abnormal aCGH result. With this, we can provide individualized risk estimates for each patient. Show more

Keywords: aCGH testing, micro-array, medical management, genetic diagnosis, genetic testing

DOI: 10.3233/PGE-13044

Citation: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 25-32, 2013

Authors: Sankararaman, Senthilkumar | Kurepa, Dalibor | Shen, Yiping | Kakkilaya, Venkatakrishna | Ursin, Sussone | Chen, Harold

Article Type: Research Article

Abstract: We report a male infant with typical clinical, pathological and radiological features of otopalatodigital syndrome type 2 (OPD 2) with a novel sequence variation in the FLNA gene. His clinical manifestations include typical craniofacial features, cleft palate, hearing impairment, omphalocele, bowing of the long bones, absent fibulae and digital abnormalities consistent with OPD 2. Two hemizygous sequence variations in the FLNA gene were identified. The variation c.5290G>A/p.Ala1764Thr has been previously reported in a patient with periventricular nodular heterotopia, but subsequently it has been reported as a polymorphism. The other variation c.613T>C/p.Cys205Arg detected in the proband has not been …previously reported and our analysis indicates that this is a novel disease-causing mutation for OPD2. Show more

Keywords: Otopalatodigital syndrome type 2, FLNA gene, filamin A

DOI: 10.3233/PGE-13045

Citation: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 33-36, 2013

Authors: Kee, Su Keyau | Hsu-Lin See, Valene | Chia, Patrick | Tan, Wei Ching | Tien, Sim Leng | Lim, Soon Tiong Alvin

Article Type: Research Article

Abstract: The t(11;22) rearrangement is the most common recurrent familial reciprocal translocation in man. Heterozygote carriers are phenotypically normal but are at risk of subfertility in the male, miscarriages, and producing chromosomally unbalanced offspring. The unbalanced progeny usually results from an extra der(22) chromosome resulting from a 3:1 malsegregation. We present here a family with t(11;22). Of six siblings, three were found to be carriers following prenatal diagnosis of the proband fetus. Neither of the two married carrier siblings have a live born child. In keeping with the prevailing knowledge of the pregnancy outcomes of heterozygote carriers, between the siblings they …had recurrent miscarriages, a fetus with a +der(22) chromosome, and other subfertility issues resulting in multiple failed in vitro fertilization cycles with preimplantation genetic diagnosis. However, unlike the siblings, their extended family comprising their heterozygote translocation mother, married aunts and an uncle had normal fertility and a lack of a history of miscarriages or an abnormal child. The differing outcomes may be related to the male partners having additional semen anomalies which may further exacerbate problems associated with the t(11;22). Because the t(11;22) rearrangement tends to run in families, it is recommended that chromosome studies are offered to family members of an affected relative as an option, and provide them with appropriate genetic counseling so that they will have the necessary information with regard to their risk for subfertility, miscarriages, and production of viable unbalanced offspring. Follow-up prenatal diagnosis should also be offered to affected expectant family members, especially after preimplantation genetic diagnosis. Show more

Keywords: Emanuel syndrome, subfertility, miscarriage, preimplantation genetic diagnosis, +der(22)t(11;22) syndrome

DOI: 10.3233/PGE-13046

Citation: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 37-42, 2013

Authors: Toral-López, Jaime | Córdoba-Cabeza, Tania | Villeda, Maricela | Cortes-Castillo, Gabriel | Zenteno, Juan Carlos

Article Type: Research Article

Abstract: Oromandibular limb hypogenesis syndrome (OMLH; OMIM 103300) encompasses a group of uncommon disorders characterized by malformations in the mouth, jaw and limbs. It has been associated with various entities such as gastroschisis, pulmonary hypoplasia, intestinal atresia, renal agenesis, hydrocephalus and other syndromes. We describe a boy of Mexican origin with features of OMLH. In addition, brain magnetic resonance imaging shows cerebral hemiatrophy and hemihypoplasia and an ipsilateral arachnoid cyst, as well as microcephaly and frontal nevus flammeus were observed. This association, to the best of our knowledge, has not been previously reported in the literature and could be part of …a same spectrum of vascular defect with OMLH. Show more

Keywords: Oromandibular limb hypogenesis syndrome, cerebral hemihypoplasia, frontal nevus flammeus, cutaneous syndactyly in hand and feet

DOI: 10.3233/PGE-13047

Citation: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 43-48, 2013

Authors: Varma, Chaitanya | Bhat, Ramesh Y. | Bhatt, Sonia

Article Type: Research Article

Abstract: Bardet-Biedl syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, obesity, polydactyly, mental retardation and hypogonadism. We present two sisters with this rare genetic condition.

Keywords: Bardet-Biedl, hypogonadism, polydactyly, retinal dystrophy, sibling

DOI: 10.3233/PGE-13048

Citation: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 49-52, 2013