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Trisomy 9P. a Brief Clinical, Diagnostic and Therapeutic Description

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Trisomy 9P. a Brief Clinical, Diagnostic and Therapeutic Description Special article Arch Argent Pediatr 2019;117(5):e473-e476 / e473 Trisomy 9p. A brief clinical, diagnostic and therapeutic description Prof. Francisco Cammarata-Scalisia ABSTRACT CLINICAL FINDINGS Trisomy 9p is characterized by the partial It is marked by delayed mental or complete duplication of the short arm of chromosome 9. It is one of the most and psychomotor development. common autosomal structural abnormalities Craniofacial dysmorphisms include in newborn infants. This is a relatively poor microbrachycephaly,1-4,7 wide gene region, so it may be more compatible anterior fontanelle,2,7 down and with survival. It is characterized by delayed 1-3,7 mental and psychomotor growth, craniofacial upward slant of palpebral fissures, 1,2,3,8 dysmorphisms, skeletal alterations, central hypertelorism, prominent nasal nervous system abnormalities, congenital heart root, bulbous nose tip,1,3,7,9 short disease, and, to a lesser extent, kidney disorders. philtrum,3 down-turned corners of To establish a diagnosis, it is necessary to 1,7-9 2,7 perform a cytogenetic study with G bands and, mouth, micrognathia, low-set 1,3 if available, fluorescence in situ hybridization ears, and malformed, protruding complemented with comparative genomic ears.2,9 The neck may be short and hybridization for a better understanding of the webbed,3 and kyphoscoliosis, genotype-phenotype correlation. Assessment 2,6 3-5 should be interdisciplinary and encompassing a lordosis, short stature are timely family genetic counseling, together with evidenced in the pre- or post- available therapeutic options in an early manner. natal period,5 in association with Key words: trisomy 9p, diagnosis, genetic counseling, delayed bone age.1,2,5 Also, limb treatment. abnormalities characterized by short 1,10 http://dx.doi.org/10.5546/aap.2019.eng.e473 fingers, clinodactyly of the fifth finger,9 and hypoplastictoe nails1 To cite: Cammarata-Scalisi F. Trisomy 9p. A brief clinical, are part of the characteristics. Less diagnostic and therapeutic description. Arch Argent commonly, central nervous system Pediatr 2019;117(5):e473-e476. abnormalities,2,4,6,7 congenital heart disease, and kidney disorders2,4,6,7 may occur. Some studies have INTRODUCTION demonstrated an association with Trisomy of the short arm of hepatoblastoma,7,9,11 hepatocellular chromosome 9 (9p) is one of the 11,12 a. Unit of Medical carcinoma, seizures, self-harming 8 9 Genetics, most common autosomal structural behavior, dysphagia, lupus Department of abnormalities in newborn infants.1 erythematosus, and the presence of Pediatrics, School A potential explanation may be that keloids.8 Table 11-4,6,13 shows potential of Medicine of this is a relatively poor gene region, Universidad de clinical findings of trisomy 9p and Los Andes, Mérida, so it may be more compatible with their respective frequency. Venezuela. survival.1-3 Trisomy 9p accounts for Central nervous system disorders the fourth most frequent autosomal must be assessed, especially in E-mail address: trisomy, after trisomies 21, 18, and Prof. Francisco patients with epilepsy and neuronal 2,4 6 Cammarata-Scalisi: 13. migration alterations. For example, francocammarata19@ It was first described in 4 patients Dandy-Walker malformation, gmail.com by Rethoré et al. in 19701-5 and then ventriculomegaly, agenesis and outlined by Centerwall and Beatty- hypoplasia of the corpus callosum,14,15 Funding: 4 None. DeSana in 1975. It is a clinically and large cisterna magna have been recognizable entity and, to date, more described.14 Conflict of interest: than 200 cases have been reported in In addition, growth hormone None. 1-6 the bibliography. It is characterized deficiency has been characterized2 Received: 9-11-2018 by the complete (Figure 1) or partial and, less frequently, insulin- Accepted: 3-25-2019 duplication of 9p.2 like growth factor-1 deficiency.2,16 e474 / Arch Argent Pediatr 2019;117(5):e473-e476 / Special article Treatment with recombinant human growth et al. proposed a shorter region located in 9p22.1 hormone may be considered in patients with → p23.3 trisomy 9p with short stature, while taking into On its side, trisomy 9pter-p11 is associated account the severity of intellectual disability with typical craniofacial characteristics,3 whereas and the potential for social inclusion. However, trisomy 9p21.1-q22-32 is related to more severe additional studies are required to establish craniofacial characteristics.2 Trisomy 9pter → the benefits of a taller stature in this group of q11-13 presents with skeletal and heart defects, in patients.5 addition to craniofacial characteristics.3 Facial clefts are uncommon, and the specific regions associated ETIOLOGY with this finding have not been clearly identified.10 In most cases, partial trisomy 9p occurs as a result of parental reciprocal translocation between chromosome 9 and other autosome.2,3,8 Therefore, phenotypic heterogeneity is correlated TABLE 1. Clinical findings of trisomy 9p and their frequency (as a percentage)1-4,6,13 to the variable size of the duplicated segment (producing trisomy 9p) and the monosomy of the Finding Frequency (%) other chromosomal segment.3,4,8 To a lower extent, Short stature 99 it is the result of a spontaneous (de novo) genetic Delayed bone age 99 alteration occurring for unknown reasons during Bulbous nose tip 95 Down-turned corners of mouth 95 early embryonic development, i.e., it is not passed Brachydactyly 90 2,8 by any of the parents. Clinodactyly 90 Based on the aforementioned information, Branchymesophalangy 90 establishing the genotype-phenotype Language disorder 90 correlation may be hindered by the presence Single palmar crease 80-95 Delayed puberty 70-90 of small deletions or duplications affecting Strabismus 70-80 other chromosomes in most reported cases Short philtrum 70-80 of trisomy 9p.2,10 Such additional genetic Hypertelorism 70-80 alterations make it difficult to understand which Malformed, low-set ears 70-80 abnormalities have been caused by trisomy 9p Microbrachycephaly 70-75 10 Hypoplasia of phalanges 70-75 or by other chromosomal changes. In some Hypoplastic nails 70-75 cases, an additional segment in the long arm of Enophthalmos 60-70 chromosome 9 may also be present.2 Down and upward slant of palpebral fissures 60-70 However, clinical severity is related to the size Gothic palate 60-70 of the duplicated segment of 9p.3,4 Studies on the Short, webbed neck 60-70 Hypotonia 60-70 genotype-phenotype correlation in cases of partial Low birth weight 50-70 trisomy 9p suggested that the critical region for Kyphoscoliosis 60 the phenotype was in 9p22 → p24, whereas Christ Lordosis 60 Mental retardation 60 Hip luxation 30-40 Cerebral hypoplasia < 30 Cerebellar hypoplasia < 30 FIGURE 1. Cytogenetic study with G bands in a female patient Ventriculomegaly < 30 with complete duplication of 9p, as shown by the arrow Agenesis and hypoplasia of the corpus callosum < 30 Choroid plexus cysts < 30 Epilepsy < 30 Congenital heart disease 25 Ventricular septal defect 25 Ebstein’s anomaly 10-20 Patent ductusarteriosus 10-20 Cleft lip and palate 5 Epicanthal folds NS Thin upper lip NS Microretrognathia NS Micropenis NS Kidney malformation Infrequent Umbilical hernia Infrequent NS: not specified. Trisomy 9p. A brief clinical, diagnostic and therapeutic description / e475 It has been suggested that the dosage effects One of the basic, complementary exams of the genes located in 9pter-q22 contribute to the that is recommended to define the phenotypic etiology of the already commented Dandy-Walker expression is a cranial (transfontanellar) malformation.15 Therefore, the genetic dosage ultrasound and, in the presence of an abnormality effects, together with environmental influences, or signs suggestive of a structural abnormality, may be responsible for several abnormalities such as seizures, a brain magnetic resonance present in the central nervous system observed imaging should be done. For the management in this entity.14 of seizures, the most adequate drug for this type of crises should be indicated. In addition, DIAGNOSIS, MANAGEMENT AND psychomotor development should be monitored TREATMENT by an interdisciplinary team, including a pediatric Diagnostic guidance should be aimed at neurologist, a physical therapist, and different confirming the existence of chromosome disease, health care providers from the early care team, initially through a cytogenetic study with G bands such as a speech therapist and an educational and, if available, with a fluorescence in situ psychologist, among others. For treatment, it is hybridization6 complemented with comparative critical to conduct interventions in relation to genomic hybridization, which is a more accurate delayed psychomotor development through early method to measure changes in the number of stimulation, which should be started as early as copies across the genome. This method is useful possible. On their part, parents’ involvement to determine the region of chromosome 9 and its in stimulation is decisive to obtain the best size, as well as other chromosomes involved, thus outcomes.6 facilitating a more comprehensive understanding Likewise, the Departments of Ophthalmology, of genotype-phenotype correlations.10,17 Cardiology, Endocrinology, Nephrology, In the presence of a structural chromosomal Traumatology and Orthopedics, and Radiology abnormality, these studies should be done in both should perform assessments for the presence patients and their parents to identify the source of hypoplasia of phalanges, among other signs,
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