Depressed Nasal Bridge Research Articles

Tympanic membrane reconstruction of a persistent perforation associated with massive myringosclerosis in a girl with achondroplasia – case report

Achondroplasia is a genetic disease connected with improper function of fibroblast growth factor receptor 3 (FGFR3) resulting in musculoskeletal disorders. Apart from characteristic musculoskeletal abnormalities (short statute with short proximal limb segments, prominent forehead, midface hypoplasia and a depressed nasal bridge) and generalized hypotonia it also affects otolaryngological field in a form of sleep-related upper respiratory tract disorders (obstructive and central apnea) and conductive hearing loss. This is the result of anatomical phenotype, together with Eustachian tube dysfunction. Interestingly, up to 25% of children with achondroplasia may fail hearing screening in one or both ears. In most cases laryngological disorders require surgical procedures, usually adenotomy, adenotonsillectomy, tonsillectomy or tube placement. Such surgical interventions increase the risk of complications, especially when repeated. We would like to present a case of a girl with achondroplasia that was qualified for myringoplasty because of persistent tympanic membrane perforation due to surgical extrusion of persistent ventilation tube, with associated massive myryngoslerosis.

Eye, Ocular Adnexa, and Facial Manifestations of Tetrasomy 18p

Tetrasomy 18p is often the result of an additional isochromosome for the short arm of chromosome 18. Although many organ systems are affected phenotypically, the ocular manifestations associated with tetrasomy 18p have not been well characterized in the literature. This case report presents the ocular and facial features associated with tetrasomy 18p in a 4-year-old Black girl, along with a review of clinical presentations previously reported in the literature. A systematic review of the literature in PubMed was conducted to summarize the reported eye, ocular adnexa, and distinctive facial features in individuals with confirmed tetrasomy 18p. Searching “Tetrasomy 18p” generated 65 article results, of which 28 articles had sufficient eye and facial descriptions. Including the patient in this report, 90 patients had confirmed tetrasomy 18p. The most common features noted in these 90 patients, with a roughly equal male-to-female ratio of impact (7:8), were as follows: microcephaly (57%), triangular facies (18%), anomalous palpebral fissures (31%), strabismus (48%), low-set ears (52%), hearing loss to some extent (16%), depressed or flat nasal bridge (18%), smooth philtrum (41%), thin upper lip (27%), and highly arched palate (21%). Additionally, many were noted to have feeding difficulties (28%), developmental delay (58%), and abnormal brain findings on imaging (20%). Muscle tone was abnormal in 23% of the patients. This report elucidates the reoccurring eye, ocular adnexa, and distinctive facial features associated with tetrasomy 18p. This knowledge may assist in timely diagnosis and encourage providers to use a multidisciplinary approach for the treatment of affected individuals. [ J Pediatr Ophthalmol Strabismus . 2021;58(6):e44–e48.]

Neonatal Osteosclerotic Bone Dysplasia (Raine Syndrome)

Background: Raine syndrome is a rare autosomal recessive neonatal osteosclerotic bone dysplasia caused due to mutations in the FAM20C gene. It has an early and aggressive onset which often results in death in the first few weeks of life, although there have been cases of patients surviving into childhood. Clinical Description: We describe the case of a neonate girl born with microcephaly, proptosis, triangular mouth, depressed flat nasal bridge, mid-face hypoplasia, low set ears, high-arched palate, and a wide-open anterior fontanelle. Based on the clinical phenotype, the differentials considered were a congenital infection and Crouzon syndrome. Management: Infantogram revealed generalized osteosclerosis. Based on the radiological phenotype, the differentials considered include Thanatophoric dysplasia, osteopetrosis, and Achondroplasia. Search for concealed anomalies revealed dysmorphic features in the brain and kidneys. The clinical exome demonstrated a heterozygous missense and heterozygous nonsense variant in exon-7 of the FAM20C gene, which established the diagnosis of Raine syndrome. Conclusion: Genetic analysis based on phenotype can aid in the early diagnosis of dysmorphic children and help in instituting appropriate management

Tetrasomy 18p in one non-identical twin born to healthy parents: A case report

Tetrasomy 18p is an extremely rare disorder with estimated incidence 1:140,000-180,000. The most common clinical presentations include developmental delay, intellectual disability, and several dysmorphic features such as the triangular face, low-set ears, depressed nasal bridge or smooth philtrum. The disease's hallmark is a small supernumerary isochromosome 18p consisting of two copies of the same arm of chromosome 18. Males and females are affected equally. Here, we present the case of 20 months old girl with tetrasomy 18p, the only affected child out of the dizygotic twins born to healthy parents. Routine cytogenetic testing revealed the presence of the marker chromosome in the girl's sample. Combination of Multicolor Banding fluorescent in situ hybridization and array-based Comparative Genomic Hybridization confirmed the isochromosome 18p in this girl. Quantitative Fluorescence PCR determined the maternal origin of the isochromosome 18p. The presented case of tetrasomy18p in one of the non-identical twins supports the hypothesis that tetrasomy 18p arises de novo and are of maternal origin. We conclude that the formation of isochromosome 18p is a random event that can occur in pregnancies of cytogenetically normal parents and maternal age is probably the main risk factor in etiology of the tetrasomy 18p.

Non-lethal Raine Syndrome Report Lacking Characteristic Clinical Features

Raine syndrome is a rare, often lethal autosomal recessive condition marked by congenital malformations that range in severity. Considering that several case reports of this syndrome describe cases of stillbirth or perinatal death, information about the clinical presentation and development of this condition in mild, non-lethal cases is lacking. With that in mind, in this case report, we describe the clinical, oro-dental, and skeletal findings of a 14-year-old Brazilian patient diagnosed with a mild form of non-lethal Raine syndrome. This patient has very mild facial dysmorphia, not displaying hypoplastic nose, micrognathia, low set ears or depressed nasal bridge, which is uncommon even in other mild, non-lethal cases of RS. Furthermore, this patient has bilateral brain calcifications and a series of oro-dental abnormalities, such as amelogenesis imperfecta and recurrent periodontal abcesses. Sanger sequencing of genomic DNA identified a homozygous missense variant c.1487C > T at exon 9 of FAM20C (NM_020223.4) in the patient. The patient's mother carries the same variant but is heterozygous. This variant predicts a proline to leucine substitution in position 496 (p.P496L, NP_064608.2) previously reported, which allows for the phenotypic comparison between these cases. This way, this case report calls attention to how differently RS can appear, highlighting the importance of new non-lethal Raine syndrome case reports to help further determine the phenotypic spectrum of this condition.

Achondroplasia: Clinical, Radiological and Molecular Profile from Rare Disease Centre, India.

Achondroplasia is the most common autosomal dominant form of skeletal dysplasia and is caused by heterozygous mutations of the fibroblast growth factor receptor 3 ( FGFR3 ) gene at region 4p16.3. This study highlights the data of achondroplasia cases, clinical spectrum, and their outcome from small cities and the region around Rajasthan. The data for analysis were collected retrospectively from genetic records of rare disease clinic in Rajasthan. Clinical profile, radiographic features, molecular test results, and outcome were collected. There were 15 cases, including eight males and seven females, in this cohort. All had facial hypoplasia, depressed nasal bridge, prominent forehead, and characteristic radiographic features. A total of 14 cases were sporadic and one case was inherited from the mother. Mutation analysis showed 13 out of 15 cases with the p.Gly380Arg mutation in the FGFR3 gene. Hydrocephalus was developed in three cases, required shunting in two cases.

CASE REPORT: ORAL MANIFESTATIONS OF YOUNG PATIENT SUFFERING FROM BOTH THALASSEMIA MAJOR AND HEPATITIS B

<h3>Introduction</h3> Thalassemia is a hereditary hemolytic anemia characterized by the inability of erythroblasts to produce the beta-chain of the hemoglobin structure. Patients with thalassemia acquire hepatitis most often from viruses contracted from blood transfusions especially in developing countries like Pakistan. This case reports the distinct oral manifestations in a young patient with thalassemia major and hepatitis B. <h3>Case Report</h3> An 8-year-old male patient visited Jinnah Sindh Dental Outpatient Department with the complaint of bleeding gums. According to the history, the patient was suffering from beta-thalassemia congenitally. Both parents were normal (carrier). He had 5 siblings of which 4 were phenotypically healthy (carriers). A 12-year-old sister had died because of beta-thalassemia. The patient had undergone regular blood transfusion from the age of 5 years. The patient was diagnosed with hepatitis 2 months ago, possibly due to contaminated blood transfusion. <h3>Clinical Findings</h3> The clinical examination showed that the patient was poorly built and undernourished with short stature. The prominent dental arch parameters evident were the characteristic appearance known as "chipmunk face" (caused by hyperplasia of bone marrow in the maxilla that exceeds the mandible). Frontal and parietal bossing with depressed nasal bridge were present. <h3>Oral Findings</h3> Intraoral examination demonstrated class II malocclusion along with maxillary protrusion. Other findings included overcrowding of mandibular anteriors, proclined upper anterior teeth, generalized yellowish discolored teeth, mild generalized diastema, and localized periodontitis affecting the lower anteriors. Multiple decayed teeth with heavy deposition of calculus and plaque on teeth with dark stains were also seen.

CASE REPORT: REPORTING THE ORO-DENTAL FINDINGS OF ELLIS-VAN CREVELD SYNDROME – A RARE GENETIC DISORDER

<h3>Introduction</h3> Ellis-van Creveld syndrome (EVC) is a rare autosomal recessive disorder, which is also known as chondroectodermal dysplasia. It is caused by genetic mutation in 2 genes: EVC1 and EVC2. The syndrome has a rare occurrence with a prevalence of 1 in 60,000 to 200,000 worldwide. EVC consists of a distinctive tetrad of various clinical manifestations: chondrodysplasia of tubular bones leading to dwarfism, polydactyly plus syndactyly, ectodermal dysplasia comprising of sparse hair together with dystrophic nails, and congenital morbus cordis commonly involving the single atrium and ventricular septal defect. In addition to the characteristic features, EVC also consists of a unique set of oral manifestations. The present case discusses the various oro-dental findings in a young patient of this rarely reported syndrome. <h3>Case Report</h3> A 7-year-old male patient visited Jinnah Sindh Dental Outpatient Department with a complaint of missing maxillary anterior teeth. In the present case, the patient had a history of consanguineous marriage of parents, supporting the recessive nature of the disorder. <h3>General Examination</h3> The general examination showed that the patient had disproportionate short stature. The limbs were short with postaxial polydactyly affecting both hands. The nails were thin and dystrophic. Other findings were hypertelorism and broad depressed nasal bridge. <h3>Oral Examination</h3> The oral examination revealed absence of mandibular anterior mucobuccal fold, mandibular hyperplastic frenula, labiogingival adhesions, serrated appearance of the gingiva, and morphological abnormalities of mandibular anterior teeth with prominent diastema. The maxillary incisors were absent. Multiple frenulum and attaching labial mucosa to alveolar mucosa were also observed.

Two Rare Syndromic Syndactyly Cases in Neonates

Abstract Introduction Isolated findings of syndactyly are benign. However, syndactyly can be associated with rare syndromes that need to be diagnosed for further management and for genetic counseling. Methods We present two cases of syndromic syndactyly in neonates. The first case is a 13-day-old female neonate with dysmorphic features. The neonate had clinical features of prominent forehead, hypertelorism, widely separated sagittal and metopic sutures, down-slanting eyes, low set ears, depressed nasal bridge, micrognathia, cleft palate, pectus excavatum, brachydactyly, and syndactyly of the second to fourth fingers bilaterally in upper limbs and in lower limbs.The second case is a 10-day-old male neonate with dysmorphism in the form of cleft alveolar ridge and palate, hyperplastic frenula, hypoplastic alar cartilage, syndactyly of the left hand, clinodactyly of the left lower limb toes, and amniotic bands. Discussion Case 1 was diagnosed as otopalatodigital syndrome because of the characteristic clinical features. This is a rare syndrome associated with syndactyly that often goes undiagnosed. Otopalatodigital syndrome spectrum disorders comprise of four phenotypically related conditions: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia, and Melnick–Needles syndrome. As it is associated with x-linked inheritance, its severity is more in males.Case 2 was diagnosed to have orofaciodigital syndrome because of the characteristic clinical features. It is another rare syndrome associated with syndactyly having abnormalities in the development of the oral cavity, face, and digits along with intellectual disability and renal system impairment. Conclusion There are fewer publications on these syndromes as they are rare and diagnosis is difficult. Recognizing these syndromes is key to further management and for genetic counseling.

An orthodontic perspective on Larsen syndrome

BackgroundLarsen syndrome (LS) is a rare disorder of osteochondrodysplasia. In addition to large-joint dislocations, craniofacial anomalies are typical characteristics. In this report, we performed orthodontic analyses, including skeletal and occlusal evaluations, to examine whether the craniofacial skeletal morphology leads to the craniofacial anomalies in LS.Case presentationA 5 year old Japanese girl who was clinically diagnosed with LS was referred to the orthodontic clinic in the Fukuoka Dental College Medical and Dental Hospital because of a malocclusion. Clinical findings at birth were knee-joint dislocations, equinovarus foot deformities, and cleft soft palate. The patient showed craniofacial anomalies with hypertelorism, prominent forehead, depressed nasal bridge, and flattened midface. To evaluate the craniofacial skeletal morphology, cephalometric analysis was performed. In the frontal cephalometric analysis, the larger widths between bilateral points of the orbitale were related to hypertelorism. The lateral cephalometric analysis revealed the midface hypoplasia and the retrognathic mandible. These findings were responsible for the flattened appearance of the patient’s face, even if the anteroposterior position of the nasion was normal. Her forehead looked prominent in relation to the face probably because of the retrognathic maxilla and mandible. Both the study model and the frontal cephalometric analysis indicated constriction of the upper and lower dental arches. The posterior crossbite facilitated by the premature contacts had developed in association with the constriction of the upper dental arch.ConclusionsThis patient had some craniofacial anomalies with characteristic appearances in LS. It was evident that the underlying skeletal morphology led to the craniofacial dysmorphism.

OTUD5 Variants Associated With X-Linked Intellectual Disability and Congenital Malformation.

BackgroundX-linked intellectual disability (XLID), which occurs predominantly in males, is a relatively common and genetically heterogeneous disorder in which over 100 mutated genes have been reported. The OTUD5 gene at Xp11.23 encodes ovarian tumor deubiquitinase 5 protein, which is a deubiquitinating enzyme member of the ovarian tumor family. LINKage-specific-deubiquitylation-deficiency-induced embryonic defects (LINKED) syndrome, arising from pathogenic OTUD5 variants, was recently reported as a new XLID with additional congenital anomalies.MethodsWe investigated three affected males (49- and 47-year-old brothers [Individuals 1 and 2] and a 2-year-old boy [Individual 3]) from two families who showed developmental delay. Their common clinical features included developmental delay, hypotonia, short stature, and distinctive facial features, such as telecanthus and a depressed nasal bridge. Individuals 1 and 2 showed epilepsy and brain magnetic resonance imaging showed a thin corpus callosum and mild ventriculomegaly. Individual 3 showed congenital malformations, including tetralogy of Fallot, hypospadias, and bilateral cryptorchidism. To identify the genetic cause of these features, we performed whole-exome sequencing.ResultsA hemizygous OTUD5 missense variant, c.878A>T, p.Asn293Ile [NM_017602.4], was identified in one family with Individuals 1 and 2, and another missense variant, c.1210 C>T, p.Arg404Trp, in the other family with Individual 3, respectively. The former variant has not been registered in public databases and was predicted to be pathogenic by multiple in silico prediction tools. The latter variant p.Arg404Trp was previously reported as a pathogenic OTUD5 variant, and Individual 3 showed a typical LINKED syndrome phenotype. However, Individuals 1 and 2, with the novel variant (p.Asn293Ile), showed no cardiac or genitourinary malformations.ConclusionsUnlike previous reports of LINKED syndrome, which described early lethality with congenital cardiac anomalies, our three cases are still alive. Notably, the adult brothers with the novel missense OTUD5 variant have lived into their forties. This may be indicative of a milder phenotype as a possible genotype-phenotype correlation. These findings imply a possible long-term prognosis for individuals with this new XLID syndrome, and a wider phenotypic variation than initially thought.

FREQUENCY OF CLINICAL FEATURES AND CYTOGENETIC DEFECTS IN DOWN SYNDROME DIAGNOSED AT AFIP

Objective: To determine the frequency of clinical features and cytogenetic abnormalities in patients of down syndrome and correlation of cytogenetic abnormalities with clinical features.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, from Feb 2017 to Feb 2018.&#x0D; Methodology: Total 163 patients with clinical suspicion of Down syndrome were selected by non-probability convenient sampling and diagnosis was confirmed by conventional cytogenetic analysis using Giemsa trypsin banding technique. Clinical features were assessed and frequency of different cytogenetic abnormalities were noted.&#x0D; Results: Out of total 163 patients, 96 (59%) were male and 67 (41%) were female. Median age of the patients was 11 months. Trisomy 21 was detected in 158 (96.9%), Robertsonian translocation in 4 (2.4%) and mosaicism in 01 (0.6%) patient. The predominant clinical features observed were slaunted with eyes, epicanthic folds, depressed nasal bridge and protruding tongue.&#x0D; Conclusion: Trisomy 21 is the most common cytogenetic abnormality observed in patients of down syndrome.

Bainbridge-Roper syndrome: A rare case of developmental delay

ASXL3 mutations were first identified in 2013 by Bainbridge et al. as a cause of syndromic intellectual disability in four children with similar phenotypes using whole-exome sequencing. The clinical features – postulated by Bainbridge et al. were developmental delay, severe feeding difficulties, failure to thrive and neurological abnormalities. To date, a total of nine individuals with BRPS have been published in the literature in four reports (Bainbridge et al., Dinwiddie et al, Srivastava et al. and Hori et al.). In this report, we describe an uncertain variant present in Exon 11 of ASXL3(+) heterozygous zygosity in a female child with clinical features: truncal muscular hypotonia with significant motor delay, profound speech impairment, intellectual disability and a characteristic dysmorphic facies phenotype (open mouth, full lips, depressed nasal bridge, metopic prominence, microcephaly (45.5.cm), with camptodactyly and dysplastic fingers). Hence, we are reporting a rare case of developmental delay.

Nasoorbitoethmoid fractures in a tertiary care hospital of eastern India: A prospective study.

Purpose:The purpose of this study was to report on the pattern of occurrence of nasoorbitoethmoid (NOE) fractures in Odisha and the various factors that influence their distribution.Methods:The study period was from January 1, 2016 to December 15, 2017. After approval from the Institutional Ethics Committee, all patients diagnosed with naso-orbito-ethmoid fractures reporting to the department of OMFS and Level-1 trauma centers were included in the study. Sociodemographic data along with the etiology and type of fracture were mentioned. Associated injuries to other body parts were noted. Open reduction was possible only in five cases of NOE fractures. The treatment plan including the operative approach and postoperative results was evaluated.Results:A total of 1192 patients with facial fracture were seen, of which 52 (4.36%) patients had NOE fractures. Males far outnumbered females in a ratio of 9:1. Thirty-three patients (63.46%) had unilateral NOE fracture, while the rest 19 (36.54%) had bilateral NOE fracture. Sixteen (30.76%) cases were classified as Type I, 35 (67.30%) as Type II, and 1 (1.92%) as Type III. Road traffic accidents were the most common cause of NOE fractures (69%), followed by fall (17%) and assault (10%). The most common neurological injury to be associated with NOE fractures was pneumocephalus (29%), followed by diffuse axonal injury (8%). Telecanthus (100%) was found to be the primary clinical feature in patients of NOE fracture, followed by a depressed nasal bridge (92%). Fracture of the nasal bone was invariably associated with NOE fracture. Complications observed due to untreated NOE fractures included a shortened and retruded nose, shortened palpebral fissures, telecanthus, and enophthalmos.Conclusion:Contemporary management of NOE complex fractures demands precise diagnosis and immediate surgical management with anatomic reduction and rigid fixation of the involved bone segments. With an improvement in socioeconomic status and increased awareness among maxillofacial surgeons, hopefully, a greater number of NOE fracture patients will avail the benefits of open reduction in future.

Xia-Gibbs Syndrome: A Review of Literature.

Xia-Gibbs syndrome (XGS) is a rare genetic disorder that has been discovered as a distinct clinical entity in the recent past. The occurrence has been attributed to the mutation of AT Hook DNA binding motif Containing 1 (AHDC1) gene that is carried on chromosome 1p36. The concerned gene participates in deoxyribonucleic acid (DNA) repair apart from other crucial functions. The mutation results in dysfunction that leads to neurodevelopmental delay. The spectrum of manifestations constitutes intellectual disabilities, hypotonia, expressive language delay, sleep difficulties, and short stature. Dysmorphic facial features include depressed nasal bridge, hypertelorism, down-slanting or up-slanting palpebral fissures, horizontal eyebrows, dysplastic dentition, thin upper lip vermilion, and micrognathia. The phenotype is still expanding. The condition may range from mild to severe dysfunction depending on the area and site of genetic aberration but variation is evident. Thus, the correlation between genotype and phenotype is largely unclear. XGS should be considered as a differential diagnosis for patients presenting with intellectual as well as developmental disabilities. Whole-exome sequencing (WES) is the genetic test that is largely used for the confirmation of diagnosis. Less is known about the natural history as only a few adults with XGS have been documented in the literature. Age-appropriate cancer screening is recommended for patients with XGS as the gene mutation alters DNA repair mechanisms that may trigger tumour formation. The management of patients diagnosed with XGS is an area that needs investigation. Though use of growth hormone replacement therapy and physiotherapy intervention have been reported as effective in previous studies, research on effective means of care of these patients is warranted on a larger number of patients. We present a review of current literature on what is known about XGS that would facilitate to identify knowledge gaps for paving a way for further studies. This, in turn, will help in provision of early and effective rehabilitation services for patients with XGS.

16194 A GAPO syndrome case report: Identification of novel biallenic ANTXR1 variants cause GAPO syndrome

GAPO syndrome (GS) is a very rare disorder characterized by growth retardation, pseudoanodontia, alopecia and optic atrophy. We report a 20-year-old boy, except optic atrophy combined with a new discovered mutation. The patient was noticed to have abnormal facial features at birth, but no one knew what was exactly abnormality. He was discovered getting this syndrome since 12-year-old. On examination, the patient had short feature, universal alopecia, redundant skin, cafe-au-lait macules on the scalp, osteomalacia, and pseudoanodontia. He also had a typical face for GS including high and bossing forehead, puffy eyelids, depressed nasal bridge, cranofacial dysmorphia, thick everted lower lip, low-set ears, premature aging appearance and prominent dilated scalp veins. Primary and permanent teeth were formed but fail to erupt. The development of his mental and motor functional activities was not discovered abnormalities on examination. Laboratory examination was normal. The histopathologic pattern of the scalp skin described the epidermis had an atrophic malpighian layer, the epidermal ridges did not descend in the dermis and there was a dense proliferation of connective tissue admixed with infiltration of a chronic inflammatory cell. New mutations were discovered including a novel biallenic variants of ANTXR1: c.T1149 A (protein Y383X) and c.1143_1145del (protein Y383del) located both in exon 15 by whole exome sequencing. These variants are inherited from paternal indicated the auto recessive mode of inheritance. To date, only 6 mutations in ANTXR1 have been reported in GS. This is a first case of GS due to a novel biallenic ANTXR1 variants.

Multiple odontogenic keratocyst: A case report and review of literature

Odontogenic keratocysts (OKCs) may occur in two different forms, either as solitary (non syndromic OKCs) or as multiple OKCs (syndromic OKCs). Multiple OKCs are usually associated with Gorlin–Goltz syndrome with features like skin carcinomas and bifid ribs, eye, and neurologic abnormalities. We report a rare case of Gorlin–Goltz syndrome in a 35-year-old male patient who presented with a swelling in lower left back teeth region since 1 week. Apart from these, other findings observed in the patient were frontal bossing, depressed nasal bridge, ocular hypertelorism, prominent supra orbital ridge, and mild mandibular prognathism. On the basis of clinical and radiological evaluation, Enucleation was planned in all the three quadrants and histopathological evaluation revealed multiple OKC’s. Patient was followed-up multiple times for the duration of six months. This case report highlights the important findings and presentation of a rare case of Gorlin Goltz syndrome along with its review of literature. Keywords: Odontogenic keratocyst, Basal cell carcinoma, Bifid ribs, Gorlin Goltz Syndrome.

Pituitary Stalk Interruption Syndrome: Baseline Characteristics and Long-Term Evolution of Two Pediatric Cases with Rare Presentation

Background and Aims&#x0D; Pituitary stalk interruption syndrome (PSIS) is characterized by the presence of a thin or absent pituitary stalk in association with a hypoplastic or aplastic anterior pituitary or an ectopic neurohypophysis [1,2]. The phenotype associated with PSIS has a high incidence of various combinations of hormonal deficiencies, sometimes associated with extra-pituitary birth defects [1]. The aim of our study is to illustrate the heterogeneity of PSIS through a complete description of the clinical, biological and imagistic differences between our cases.&#x0D; Case Reports&#x0D; We describe two rare pediatric cases. The first case was a 6-year-old boy admitted to our department with polyuro-polydipsic syndrome and underdeveloped external genitals. He had a history of neonatal micropenia and a family medical history of panhypopituitarism and midline malformations. Physical examination revealed normal stature (height: 117 cm, −0.4 SDS), obesity (BMI: 25.2 Kg/mp, over 97th percentile), micropenia (stretched penile length: 3 cm) and non-palpable testes. Initially, his urine output was 5000 mL/24 h, with a low urine specific gravity of 1005–1010, and no increase after water deprivation test, with an appropriate response after desmopresin administration. He presented normoglycemia. Serum gonadotropin (FSH, LH) and testosterone levels were low, with no response after GnRH-analogue stimulation test. IGF-1 levels were low-normal. His Copeptin value was decreased. Pituitary MRI showed anterior pituitary hypoplasia, absence of the pituitary stalk and neurohypophysis.&#x0D; The second case was a 4-year-old girl referred to our service for growth retardation. She had a history of neonatal prolonged jaundice and intermittent seizures, for which she was prescribed phenobarbital for 2 years. Her physical examination described short stature (height: 90.5 cm, −3.3 SD), underweight (BMI: 15.87 Kg/m2, 15–25th percentile), head dysmorphic features: medial epicanthal fold, depressed nasal bridge, anteverted nares, ogival palate. She had a bone age of 2 years. The initial evaluation diagnosed severe GH deficiency, and during the next 3 years of follow-up she developed ACTH, TSH and FSH-LH deficiencies. MRI examination indicated anterior pituitary hypoplasia, absence of pituitary stalk and ectopic neurohypophysis.&#x0D; Discussion&#x0D; Central diabetes insipidus is rarely reported in patients with PSIS (0–4%) [1,3]. Although GH deficiency was found almost ubiquitous in PSIS, our first patient had no growth retardation. Normal linear growth despite abnormal GH secretion was also reported [4]. Neonatal cholestasis was linked to ACTH deficiency, which can also be a cause of recurrent hyponatremia [1]. There were no signs of ACTH deficiency or hyponatremia in our second patient in the neonatal period. Few reports showed cases of PSIS that were diagnosed with acute epileptic seizures accompanied by hyponatremia [5]. The rapidly progressive evolution to combined pituitary deficiency observed in PSIS cases [4] with neonatal features was also recognized in our patients.&#x0D; Conclusions&#x0D; The phenotype associated with PSIS can be highly heterogeneous. It is important to increase the awareness of PSIS, especially in the neonatal period when the features of PSIS can be easily overlooked. We also emphasize the importance of patient follow-up as an essential part of an adequate management.

Dental and Craniofacial Characteristics in Patients With 14Q22.1-Q22.2 Deletion: A Case Series.

This case series is a follow-up report focusing on dental and facial characteristics in patients with a rare microdeletion in chromosome 14q22.1-q22.2. Usually, these patients have severe ocular, brain, and digital abnormalities. However, this case series shows that clinical presentation can be mild. Four relatives spanning 3 generations were diagnosed with a familial autosomal dominant 2.79 Mb microdeletion in chromosome 14q22.1-q22.2. Genetic screening was done by the Bacterial Artificial Chromosome array-comparative genome hybridization and was confirmed by the fluorescence in situ hybridization technique. Dental and craniofacial data were collected from medical files, clinical examinations, clinical photos, panoramic and cephalometric radiographs, and dental casts. Written informed consent for scientific use was obtained for all family members. No larger syndrome could be identified. All cases had similar facial red flag characteristics, consisting of a long face with retrognathia and open mouth relation, associated oral clefts in varying degrees, depressed nasal bridge, delayed tooth development, hypertelorism, and low-set angular ears. The dental casts showed a distal molar occlusion and a lack of space in the dental arches. Developmental delay was noted together with limb defects such as poly- and syndactyly. Microphthalmia and hearing loss were present in the most severe cases. This rare congenital disorder, associated with facial dysmorphia, oral clefts, and tooth agenesis, can remain undiagnosed until adulthood. A family history of short stature, developmental delay, poly- or syndactyly, and micropthalmia are suggestive features. Similar reports help to raise awareness among dental practitioners, leading to an early genetic diagnosis.

VP32.09: Bilateral diaphragmaitc hernia in a case of Cornelia de Lange syndrome

A 38-year-old was sent to our unit for the first trimester scan at 12 weeks pregnancy. The first trimester calculated risk for trisomies was high; b-HCG-0,6 and PAPP-A-0,3. Subsequent amniocentesis revealed normal caryotype 46 XY. Array-comparative genomic hybridisation study didnt reveal any abnormality as well. Our scanning at 12 and 20 weeks revealed severe micrognathia (at 12 weeks) with mandibular spur (20 weeks), dysmorphic facial features such as hypertelorism, long convex philtrum, anteverted nares, depressed nasal bridge, thin lips with downturned lip corners at 20 weeks. Scanning at 20 weeks also revealed bilateral diaphragmatic hernia, stomach and bowel loops located in the left hemithorax, liver located in the right and left hemithorax, anterior displacement of the heart with minimal lateral shift, diaphragm was visible only at its anterior part, small hands with brachydactyly, cleft palate was suspected. After TOP the WES test revealed heterozygous mutation in exon 10 in the NIPBL gene resulting in a frameshift mutation, which is associated with Cornelia de Lange syndrome. Postmortem appearance of the abortus revealed also bushy eyebrows with synophrys, small hands and cleft palate. Diaphragm was presented only at its anterior part. Bilateral diaphragmatic hernia was confirmed. Supporting information can be found in the online version of this abstract Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.