High Arched Palate Research Articles

Late-onset nephrotic syndrome with thyroid hypoplasia and nup85 mutation in Galloway-Mowat syndrome: A case report

Galloway-Mowat syndrome is an autosomal recessive rare hereditary disorder with progressively worsening renal function, neurological and psychomotor abnormalities, microcephaly, facial dysmorphism, and thyroid, adrenal, and ovarian hypoplasia/agenesis. Here, we present the case of a 9-year-old girl who presented with late-onset steroid-resistant nephrotic syndrome with rapid worsening of renal function, microcephaly, hypertelorism, high-arched palate, delayed speech and developmental milestones, poor intellectual function, short stature, hypertension, and hypothyroidism. Magnetic resonance imaging brain was suggestive of cerebral and cerebellar atrophy, hypomyelination, and optic atrophy. Renal biopsy was suggestive of focal segmental glomerulosclerosis. Whole-genome exon sequencing revealed a homozygous mutation in the NUP85 gene. The clinicians should be aware of this rare syndrome and consider it as a possibility in any patient presenting with nephrotic syndrome, microcephaly, and neurological abnormality.

Custom fabrication of cast splint microimplant-assisted rapid palatal expansion appliances for treatment of maxillary deficiency in young adults

Background: The objective of this article was to illustrate the process in the fabrication of a custom cast splint Microimplant-Assisted Rapid Palatal Expansion (MARPE) appliance for treatment of maxillary deficiency in young adults. Findings: The fabrication of a custom-made MARPE appliance allows the casting base to design according to the shape of the patient’s palate close to the palatal mucosa. In this new design, one end consists of a casting body, inserting hole, and teeth retention device (circumferential rings) connected to the other end by a jackscrew. Connection of all parts in the integral casting unit increases the strength of the expansion appliance and avoids distortion, deformation, or damage to the palatal mucosa due to increased resistance from the oromaxillofacial area. Conclusion: This custom design can improve the clinical outcome of maxillary expansion, especially in patients with narrow and high-arched palates.

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

Cytogenomic characterization of a de novo 4q34.1 deletion in a girl with mild dysmorphic features and a coagulation disorder

Background4q deletion syndrome is a rare chromosomal disorder that mostly arises de novo. The syndrome is characterized by craniofacial dysmorphism, digital abnormalities, skeletal alterations, heart malformations, developmental delay, growth retardation, Pierre Robin sequence, autistic spectrum and attention deficit-hyperactivity disorder, although not every patient shows the same features. Array comparative genomic hybridization (aCGH) use improves the detection of tiny chromosomal deletions and allows for a better understanding of genotype–phenotype correlations in affected patients. We report the case of a 6-year-old female patient showing mild dysmorphic features, mild mental disabilities and a coagulation disorder as a consequence of a de novo del(4)(q34.1) characterized by aCGH.Case presentation A 6-year-old female patient exhibited special craniofacial features, such as backward-rotated ears, upslanted palpebral fissures, broad nasal bridges, anteverted nares, broad nasal alae, smooth philtrums, smooth nasolabial folds, thin lips, horizontal labial commissures, and retrognathia. In the oral cavity, maxillary deformation, a high arched palate, agenesis of both mandibular canines and fusion of two mandibular incisors were observed. She also displayed bilateral implantation of the proximal thumbs, widely spaced nipples, dorsal kyphosis, hyperlordosis, and clitoral hypertrophy. In addition, the patient presented with coagulopathy, psychomotor delay, attention deficit-hyperactivity disorder, and mild mental disability. A chromosomal study showed the karyotype 46,XX,del(4)(q34.1), while an aCGH analysis revealed an 18.9 Mb deletion of a chromosome 4q subtelomeric region spanning 93 known genes.ConclusionThe clinical manifestations of this patient were similar to those reported in other individuals with 4q deletion syndrome. Although most of the patients with a 4q34 terminal deletion share similarities, variations in phenotype are also common. In general, clinical effects of chromosomal deletion syndromes depend on the length of the deleted chromosomal segment and, consequently, on the number of lost genes; however, in all of these syndromes, there is no simple correlation between the phenotype and the chromosomal region involved, particularly in cases of 4q deletion.

Reinvestigation on Newer Facts to Anticipate, Avoid And Mitigate The Development of Post-Dural Puncture Headache-A Prospective Cohort Study

Purpose: Various researchers have described the size and the type of spinal needle used for neuraxial anesthesia as the most common risk factor for developing postdural puncture headache (PDPH). Even though the occurrence of the PDPH is rare in modern anesthesia practice, we come across many such patients despite following all guidelines or precautions. Patient-related factors for developing PDPH are relatively understudied. For that, clinical features commonly present in such patients may require a thorough investigation. Methods: This prospective cohort study included fifty patients admitted for lower extremities orthopedic surgeries and developed PDPH following the neuraxial blockade. We screened all patients in this study for the presence or absence of common manifestations suggestive of connective tissue disorders (CTD). The other outcomes, like the effect of spinal needle size/type to develop PDPH and time to develop PDPH, were also measured. Results: Almost all PDPH patients included in this study had common features suggestive of CTD: the ligamentous laxity (96%), high-arched palate (96%), the blue sclera (45%), joint hyperextensibility (82%), and ejection clicks (64%). PDPH occurred more frequently with the 25G spinal needle of Quincke type than 27G of Whitacre type (82% vs. 18%). The mean (SD) headache freedom time was 73.14 (24.74) hours. Conclusions: The CTD might also be a causative factor responsible for the development of PDPH in some individuals. It can be considered a risk factor to anticipate, avoid, and mitigate the development of PDPH.

See Spots? Look Deeper!

See Spots? Look Deeper!

A ZFHX4 mutation associated with a recognizable neuropsychological and facial phenotype

Several patients with chromosomal deletions including ZFHX4 gene have been described, whereas point mutations are very rare. This gene encodes for a transcription factor involved in the development of several embryonal processes, including brain differentiation. Patients with 8q21.11 deletions usually show intellectual disability, short stature, peculiar facial features, and severe eye abnormalities. We describe a female patient with mild intellectual disability, autism spectrum disorder, strabismus, ptosis, low-set and prominent ears, high-arched palate, microretrognathia. Clinical Exome Sequencing revealed the presence of a de novo heterozygous variant in ZFHX4. Therefore, we further investigate the different phenotypes of ZFHX4 mutations and 8q21.11 deletions.

Oro-Dental Manifestations in a Pediatric Patient Affected by Helsmoortel-Van der Aa Syndrome

Aim: Aim of this case report is to describe oro-facial abnormalities in a patient affected by Helsmoortel-Van der Aa syndrome, a rare autism syndrome, with not well described dental and cranial malformations. Case Report: Helsmoortel-Van der Aa Syndrome is a rare autosomal genetic syndrome causing mental impairment and autism, craniofacial dysmorphism, chest deformity and multiple organs dysfunction. Oro-facial involvement in Helsmoortel-Van der Aa syndrome has not been thoroughly described yet. The present article reports a case of a 9 years old male patient affected by Helsmoortel-Van der Aa Syndrome, presenting with oral breathing typical facies, high arched palate, II class and dental crowding. The patient teething was adequate to his age. The enamel of incisors and molars showed demineralization areas and dark spots, a clinical picture consistent with molar incisor hypomineralization syndrome. These hypo-mineralized areas are more susceptible to cavities, in fact the patient’s 4.6 tooth was decayed. The child was brought to our attention due to a mucocele on the lower lip, confirmed by histopathologic examination. Available data on oro-dental manifestation of this syndrome are rather poor and inconsistent, also due to the rarity of the disease. The finding of enamel abnormalities in the presented case could suggest a potential genetic etiopathogenesis linked to the same genes causing Helsmoortel-Van der Aa syndrome.

Diaphyseal and Metaphyseal Modeling Defects-Clinical Findings and Identification of WRAP53 Deficiency in Craniometadiaphyseal Dysplasia.

Background: Diaphyseal and metaphyseal modeling defects lead to severe changes in bone mass and shape, which are common features in osteoporosis that linked to non-vertebral fractures. Original mechanism of diaphyseal and metaphyseal modeling defects has proved elusive. Studying rare syndromes can elucidate mechanisms of common disorders and identify potential therapeutic targets.Methods: We evaluated a family pedigree with craniometadiaphyseal dysplasia (CRMDD, OMIM 269300), a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and absent of normal metaphyseal flaring and diaphyseal constriction. Systemic radiographic examination and serum hormone test were made for this rare disease. One patient and her two normal parents were examined by means of whole-exome sequencing (WES) to identify the candidate pathogenic gene and rule out mucopolysaccharidosis and Prader–Willi Syndrome by means of Sanger sequencing.Results: There are several conspicuous radiographic characteristics: (1) bullet-shaped phalanges, (2) long and narrow pelvic inlet, absent of supra-acetabular constriction, (3) round rod-shaped long tubular bones, (4) prominent aiploic mastoid, (5) bending-shaped limb, genua varus and genu varum, and (6) congenital dislocation of elbow. Here, we did not find any wormian bones, and there are several typical clinical characteristics: (1) macrocephaly and wide jaw, (2) Avatar elf-shaped ears, pointed and protruding ears, (3) hypertrophy of limbs, (4) flat feet and giant hand phenomenon, (5) nail dystrophy, (6) limb deformity, (7) high-arched palate, (8) superficial hemangiomas, (9) tall stature, and intellectual disability. In this patient, we found biallelic frameshift deletion mutations in WRAP53, and those two mutations were transmitted from her parents respectively.Conclusions: We describe her clinical and radiological findings and presented a new subtype without wormian bones and with a tall stature. Our study showed that craniometadiaphyseal dysplasia was caused by a deficiency of WRAP53 with autosomal recessive inheritance.

Mutation in ZDHHC15 Leads to Hypotonic Cerebral Palsy, Autism, Epilepsy, and Intellectual Disability.

ObjectiveTo determine whether mutations reported for ZDHHC15 can cause mixed neurodevelopmental disorders, we performed both functional studies on variant pathogenicity and ZDHHC15 function in animal models.MethodsWe examined protein function of 4 identified variants in ZDHHC15 in a yeast complementation assay and locomotor defects of loss-of-function genotypes in a Drosophila model.ResultsAlthough we assessed multiple patient variants, only 1 (p.H158R) affected protein function. We report a patient with a diagnosis of hypotonic cerebral palsy, autism, epilepsy, and intellectual disability associated with this bona fide damaging X-linked variant. Features include tall forehead with mild brachycephaly, down-slanting palpebral fissures, large ears, long face, facial muscle hypotonia, high-arched palate with dental crowding, and arachnodactyly. The patient had mild diminished cerebral volume, with left-sided T2/FLAIR hyperintense periatrial ovoid lesion. We found that loss-of-function mutations in orthologs of this gene cause flight and coordinated movement defects in Drosophila.ConclusionsOur findings support a functional expansion of this gene to a role in motor dysfunction. Although ZDHHC15 mutations represent a rare cause of neurodevelopmental disability, candidate variants need to be carefully assessed before pathogenicity can be determined.

Desaturation during Feeding in a Term Neonate Due to 20P Duplication Syndrome

Background: Feeding problems are common in preterm neonates of which desaturation during direct feeding is a known entity. However, term newborns have acceptable range of fall in saturation while feeding directly. Here, we report a term newborn with dysmorphic features had desaturation during feeding. Clinical Description: A male baby born to second-degree consanguineous parents at term who was managed for transient tachypnea of newborn had fall in saturation beyond acceptable range during feeding. He had low set ears, high-arched palate, thin upper lip, clinodactyly, and anal tag. Management: The baby was subjected for thorough exploration of respiratory/gastrointestinal/neurological systems which did not reveal attributable findings. Clinical exome sequencing revealed 20p duplication. He was started on orogastric feeding and could be gradually changed to direct feeding at 4 months of age. Conclusions: This report may improve the understanding toward approach to feeding problems in term neonates and also about phenotypic features of 20 p duplication which is less reported.

Large Deletions and Novel Mutations in Genes Coding for Ribosomal Proteins (RPL11, RPL35A, RPS19) in the Czech National Registry of Diamond-Blackfan Anemia (DBA)

Background: 50-70% cases of Diamond-Blackfan anemia (DBA) are underlied by mutations in genes coding for ribosomal proteins (RP), however, the etiology remains unexplained in the remaining patients. Recently, rare aberrations involving extraribosomal genes (e.g., GATA1, TSR2, MCM2, FLNB) have been reported as causative for DBA. Up to 10% of all DBA patients harbor large deletions involving some of the RP genes, which were not previously identified by sequencing.Patients and Methods: Czech National Registry, containing data of 56 patients with DBA from Czechia and Slovakia (both children and adults), has a high detection rate of RP gene mutations (currently 82%). Using exome sequencing (Agilent SureSelect v6 Kit, HiSeq 2500 sequencer, Illumina) and array comparative genomic hybridization (aCGH, SurePrint G3 CGH+SNP microarray, 4x180K, Agilent), we examined periferal blood samples of patients without any proven mutation in RP genes. Identified mutations were verified by Sanger sequencing at the gDNA and cDNA level and their functional impact was studied in a cell culture (RPS11-deficient MRC-5 fibroblasts).Results: Novel mutations, previously unpublished and unrecorded in gene databases, or large deletions involving RP genes were found in 5 patients with DBA:1)In a 10-year-old female with growth and developlmental delay, severe skeletal anomalies (hypertelorism, high-arched palate, low-set ears, triphalangeal thumbs) and with a markedly elevated activity of erythrocytic adenosine-deaminase (eADA), a large deletion in 1p36 chromosomal region - arr[hg19] 1p36.12p36.11(22308520_24074348)x1 - involving the RPL11 gene was found. Depletion of RPL11 in a cellular model resulted in attenuation of proteosynthesis and cell cycle and in the disruption of nucleolar morphology.2) In a 4-year-old female with transfusion-dependent DBA, large deletion of the 3q29 region - arr[hg38] 3q29(194309533_197837049)x1 - including the RPL35A gene was detected. The patient's height is at the 10th percentile, but her weight is below the 3rd percentile. Mild intellectual disability and both atrial and ventricular septal defect are present.3) A 4,5-year-old male with transfusion dependency, iron overload and hepatopathy harbors mutation in RPS19 - hg38[19:41869031_C>T], RPS19 p.A58V. The patient's father with an identical mutation required repeated blood transfusions in childhood (until 6 years of age) due to hypoplastic erythropoiesis. To date, all parameters of his blood count are normal without any intervention, only his eADA level is slightly elevated.All above mentioned patients are treated with leucine.4) A 3-year-old male with normal phenotype harbors mutation hg38[19:41860841_A>T] in RPS19 leading to premature stop codon K23Stop.5) Mutation in RPS19 : c.[3G>A], p.M1I in an 1 year old boy whose DBA is transfusion dependent and resistant to steroids.Conclusion: Together with next generation sequencing, aCGH examination is essential for detection of novel genetic defects in DBA due to its capacity to detect larger chromosomal aberrations. Reports on 3q29 deletions involving RPL35A are scarce (only 7 cases published to date). Suggested connection between deletions, leading to haploinsufficiency of RP genes, and growth retardation (Kuramitsu et al., Blood 2012) was confirmed only for RPL11 but not for RPL35A in our study. Phenotypic differences between family members harboring the novel identical RPS19 aberration are probably influenced by epigenetic regulation and we have already observed this phenomenon in individuals with RPS7 and RPS19 mutation (Maceckova et al., ASH 2016).Supported by: AZV 16-32105A, NPU LO 1304, GA15-13732S DisclosuresNo relevant conflicts of interest to declare.

Use of facial stereophotogrammetry as a screening tool for pediatric obstructive sleep apnea by dental specialists.

To evaluate facial 3-dimensional (3D) stereophotogrammetry's effectiveness as a screening tool for pediatric obstructive sleep apnea (OSA) when used by dental specialists. One hundred forty-four participants aged 2-17 years, including children fully diagnosed with pediatric OSA through nocturnal polysomnography or at high-risk or low-risk of pediatric OSA, participated in this study. 3D stereophotogrammetry, Craniofacial Index, and Pediatric Sleep Questionnaire were obtained from all participants. Ten dental specialists with interest in pediatric sleep breathing disorders classified OSA severity twice, once based only on 3D stereophotogrammetry and then based on 3D stereophotogrammetry, Craniofacial Index, and Pediatric Sleep Questionnaire. Intrarater and interrater reliability and diagnostic accuracy of pediatric OSA classification were calculated. A cluster analysis was performed to identify potential homogeneous pediatric OSA groups based on their craniofacial features classified through the Craniofacial Index . Intrarater and interrater agreement suggested a poor reproducibility when only 3D facial stereophotogrammetry was used and when all tools were assessed simultaneously. Sensitivity and specificity varied among clinicians, indicating a low screening ability for both 3D facial stereophotogrammetry, ranging from 0.36-0.90 and 0.10-0.70 and all tools ranging from 0.53-1.0 and 0.01-0.49, respectively. A high arched palate and reversed or increased overjet contributed to explaining how participating dental clinicians classified pediatric OSA. 3D stereophotogrammetry-based facial analysis does not seem predictive for pediatric OSA screening, alone or combined with the Pediatric Sleep Questionnaire and Craniofacial Index when used by dental specialists interested in sleep-disordered breathing. Some craniofacial traits, more specifically significant sagittal overjet discrepancies and an arched palate, seem to influence participating dental specialists' classification. Fernandes Fagundes NC, Carlyle T, Dalci O, etal. Use of facial stereophotogrammetry as a screening tool for pediatric obstructive sleep apnea by dental specialists. J Clin Sleep Med. 2022;18(1):57-66.

The Nasoseptal Flap for Reconstruction of Lateral Oropharyngectomy Defects: A Clinical Series.

To study use of the nasoseptal flap (NSF) to reconstruct lateral transoral robotic surgery (TORS) oropharyngectomy defects. Retrospective case series. A clinical series of six patients undergoing NSF reconstruction of lateral TORS oropharyngectomy defects was retrospectively studied. All patients underwent TORS for the treatment of intermediate-risk human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma of the lateral pharyngeal wall between January and June 2017. All patients underwent NSF reconstruction of lateral TORS defects with retrospective analysis of outcomes and complications. Six patients underwent NSF reconstruction of lateral TORS defects. Operative times decreased from 180 minutes to 90 minutes over the study period. There were two cases of partial flap dehiscence and partial necrosis. There were no major donor site complications. All patients had temporary nasal obstruction and crusting. Two experienced temporary aural fullness. In all patients, the lateral wall was mucosalized in 1-3 weeks. Cephalometric analysis of preoperative imaging revealed that patients with high-arched palates (>3 cm) and defect lengths that are longer than NSF flap lengths are poor candidates for this technique. This NSF is a vascularized, locoregional rotational flap that can reconstruct lateral TORS defects in salvages cases or those where the parapharyngeal carotid or mandibular bone are exposed. Postoperative morbidity is limited to temporary nasal dyspnea, aural fullness, and crusting. Preoperative imaging can determine which patient will have successful defect coverage. 4 Laryngoscope, 132:53-60, 2022.

A Report of Incontinentia Pigmenti in an 11-year-old Girl

Introduction: Incontinentia pigmenti (IP) is a rarely diagnosed x-linked dominant disease affecting tissues of ectodermal and mesodermal origin such as cutaneous tissues, teeth, eyes, hair, and the central nervous system. Dermatologic manifestations are often the first signs observed in patients diagnosed with IP and are present in nearly all the subjects, but they are less harmful and do not require treatment. Oral manifestations in patients diagnosed with IP might affect both the deciduous and permanent teeth, with tooth shape anomalies and hypodontia, delayed tooth eruption, cleft palate, and high arched palate. These oral abnormalities influence feeding, quality of life (QoL), and self-esteem of the patient but can be successfully corrected by oral rehabilitation. Case Presentation: Here, we report the case of a female patient, aged 11 years, presenting with dental manifestations such as hypodontia, conical teeth, delayed tooth eruption, narrow and atrophic dental ridge, and also some non-dental findings of IP. Her dental ‎management included oral hygiene instructions, extraction of all unrestorable primary molars, and composite filling of all primary canines. Conclusions: A removable space maintainer was constructed for the patient, which resulted in favorable esthetic outcomes, proper re-establishment of mastication, and improved self-esteem.

Impaired glucose-1,6-biphosphate production due to bi-allelic PGM2L1 mutations is associated with a neurodevelopmental disorder

SummaryWe describe a genetic syndrome due to PGM2L1 deficiency. PGM2 and PGM2L1 make hexose-bisphosphates, like glucose-1,6-bisphosphate, which are indispensable cofactors for sugar phosphomutases. These enzymes form the hexose-1-phosphates crucial for NDP-sugars synthesis and ensuing glycosylation reactions. While PGM2 has a wide tissue distribution, PGM2L1 is highly expressed in the brain, accounting for the elevated concentrations of glucose-1,6-bisphosphate found there. Four individuals (three females and one male aged between 2 and 7.5 years) with bi-allelic inactivating mutations of PGM2L1 were identified by exome sequencing. All four had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals. Analysis of the children’s fibroblasts showed that glucose-1,6-bisphosphate and other sugar bisphosphates were markedly reduced but still present at concentrations able to stimulate phosphomutases maximally. Hence, the concentrations of NDP-sugars and glycosylation of the heavily glycosylated protein LAMP2 were normal. Consistent with this, serum transferrin was normally glycosylated in affected individuals. PGM2L1 deficiency does not appear to be a glycosylation defect, but the clinical features observed in this neurodevelopmental disorder point toward an important but still unknown role of glucose-1,6-bisphosphate or other sugar bisphosphates in brain metabolism.

Increased Prevalence of Minor Physical Anomalies Among the Healthy First-Degree Relatives of Bipolar I Patients - Results With the Méhes Scale.

Minor physical anomalies are somatic markers of aberrant neurodevelopment, so the higher prevalence of these signs among the relatives of bipolar I patients can confirm minor physical anomalies as endophenotypes. The aim of the study was to evaluate the prevalence of minor physical anomalies in first-degree healthy relatives of patients with bipolar I disorder compared to normal control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 20 first-degree unaffected relatives of patients with the diagnosis of bipolar I disorder and as a comparison 20 matched normal control subjects were examined. Minor physical anomalies were more common in the ear, head, mouth and trunk regions among the relatives of bipolar I patients compared to normal controls. By the differentiation of minor malformations and phenogenetic variants, we have found that both minor malformations and phenogenetic variants were more common among the relatives of bipolar I patients compared to the control group, while individual analyses showed, that one minor malformation (sole crease) and one phenogenetic variant (high arched palate) were more prevalent in the relative group. This is the first report in literature on the increased prevalence of minor physical anomalies among the first-degree unaffected relatives of bipolar I patients. The study support the concept, that minor physical anomalies can be endophenotypic markers of bipolar I affective disorder.

Biallelic Pathogenic Variants in TNNT3 Associated With Congenital Myopathy.

ObjectivePathogenic variants in TNNT3, the gene encoding fast skeletal muscle troponin T, were first described in autosomal dominant distal arthrogryposis type 2B2. Recently, a homozygous splice site variant, c.681+1G>A, was identified in a patient with nemaline myopathy and distal arthrogryposis. Here, we describe the second individual with congenital myopathy associated with biallelic TNNT3 variants.MethodsClinical exome sequencing data from a patient with molecularly undiagnosed congenital myopathy underwent research reanalysis. Clinical and histopathologic data were collected and compared with the single reported patient with TNNT3-related congenital myopathy.ResultsA homozygous TNNT3 variant, c.481-1G>A, was identified. This variant alters a consensus splice acceptor and is predicted to affect splicing by multiple in silico prediction tools. Both the patient reported here and the previously published patient exhibited limb, bulbar, and respiratory muscle weakness from birth, which improved over time. Other shared features include history of polyhydramnios, hypotonia, scoliosis, and high-arched palate. Distal arthrogryposis and nemaline rods, findings reported in the first patient with TNNT3-related congenital myopathy, were not observed in the patient reported here.ConclusionsThis report provides further evidence for the association of biallelic TNNT3 variants with severe recessive congenital myopathy with or without nemaline rods and distal arthrogryposis. TNNT3 sequencing and copy number analysis should be incorporated into the workup of congenital myopathies.

Marfan’s Syndrome with Tetralogy of Fallot in an Adult Female with Bronchiectasis

Marfan’s syndrome is an autosomal dominant genetic disorder related to a mutation in fibrillin gene type 1 involving mainly the cardiovascular, ocular, skeletal, and pulmonary systems. A 22-year-old female patient presented with cough, blood-stained sputum, and fever for 4 months. The patient was tall and on skeletal examination, high arched palate, arm-span longer than height, positive finger thumb sign, arachnodactyly, asymmetrical chest, and skin striae were present. Family history of Marfan’s syndrome was present. Echocardiography showed large ventricular septal defect with aortic override and severe pulmonary stenosis. CECT thorax showed bronchiectasis changes. Marfan’s syndrome with cardiovascular abnormalities usually has aortic dilatation, aortic regurgitation, aortic aneurysm, mitral valve prolapse, mitral regurgitation, etc. In this case, the patient has Marfan’s syndrome with tetralogy of Fallot (TPF) and bronchiectasis. The association of TOF with Marfan’s syndrome is one of the rarest findings.

FRASER SYNDROME: A CASE REPORT

Fraser syndrome (cryptophthalmos syndrome) is a congenital anomaly in which cryptophthalmos is the main feature. Other malformations can include syndactyly, craniofacial and urogenital anomalies. It is a rare autosomal recessive condition with FRAS1, FREM2 and GRIP1 genes mutation. We report a case of 2 months old male child born to consanguineous parents. He presented with unilateral cryptophthalmos and some features that were compatible with diagnostic criteria of Fraser syndrome such as syndactyly, high arched palate with ankyloglossia, cryptorchidism and hypospadias. It can be diagnosed by antenatal ultrasound and clinical examination. We also present the criteria for diagnosing Fraser syndrome, its prenatal findings and ocular management.