Low Nasal Bridge Research Articles

Severe manifestation of foetal alcohol syndrome – case report

Foetal alcohol syndrome is a term describing the set of conditions caused by maternal alcohol consumption in pregnancy. A complete evaluation includes an assessment of the three key diagnostic criteria – central nervous system damage, growth deficiency, and characteristic facial features (microcephaly, small palpebral fissures, low nasal bridge, smooth philtrum, thin upper lip). A premature one-day-old female infant with dysmorphic features, in severe general condition, was admitted to the Neonatal Intensive Care Unit due to respiratory distress and suspected heart defect. Hypotrophy, bronchopulmonary dysplasia, and both ventricular and atrial septal defect were diagnosed. The authors of this paper aim to raise awareness about the lifelong and irreversible nature of foetal alcohol syndrome, which significantly impacts various aspects of a child’s life. However, it is also highlighted that foetal alcohol syndrome belongs to a small group of conditions that can be entirely prevented.

The Intraoral Findings of the Patient with Robinow Syndrome and the Related Dental Treatment Approaches: A Case Report

Initially defined by Robinow et al. in 1969, Robinow syndrome is an exceptionally uncommon (1:500,000) hereditary disorder showing five distinct phenotypes. Although skeletal system symptoms are intense in all phenotypes, maxillofacial indications and genital organ hypoplasia are also present. Maxillofacial appearances can be listed as follows: hypertelorism, midface hypoplasia, wide and flat nose, low nasal bridge, downturned oral commissures, low-set ears, and micrognathia. In oral manifestations, gingival hyperplasia, tongue, and dental abnormalities are frequently encountered. The detection of intraoral and extraoral findings by the dentist plays a significant role in the diagnosis of this disease. Additionally, every new case documented will help dentists plan treatment approaches. Therefore, in this case report we aimed to describe the manifestations of a patient with Robinow syndrome who was referred to us by a pediatric cardiologist for her dental treatments and also the treatment approach under general anesthesia.

Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias.

We present a Pakistani kinship afflicted with a syndrome with features including short stature, reduced sitting height, orofacial symptoms including prominent forehead and thick eyebrows, short and broad thorax, and variable features such as long philtrum, short broad neck, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Phenotypic variation even within different sibships was considerable. The unique combination of the phenotypic characteristics prompted us to determine the shared homozygosity regions in patient genomes and the pathogenic variants by next generation technologies like single nucleotide polymorphism (SNP) genotyping and whole exome sequencing (WES). Through these analyses, we detected homozygous OBSL1 c.848delG (p.Gly283AlafsTer54) as the causal variant. Biallelic variants in OBSL1 are known to cause Three M Syndrome 2 (3M2), a rare disorder of growth retardation with characteristic facial dysmorphism and musculoskeletal abnormalities. Affected members of the family do not have the 3M2 hallmark features of dolichocephaly, hypoplastic midface, anteverted nares, low nasal bridge, pectus excavatum, sacral hyperlordosis, spina bifida occulta, anterior wedging of thoracic vertebrae, prominent heels, and prominent talus. Moreover, they have some variable features not typical for the syndrome such as round face, disproportionate short stature, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Our study facilitated genetic diagnosis in the family, expanded the clinical phenotype for 3M2, and unraveled the considerable clinical variation within the same kinship. We conclude that unbiased molecular analyses such as WES should be more integrated into healthcare, particularly in populations with high parental consanguinity, given the potential of such analyses to facilitate diagnosis.

P-708 Establishment of linkage phase, using Oxford Nanopore Technologies, for Preimplantation Genetic Testing of Coffin-Lowry syndrome with a de novo RPS6KA3 mutation

Abstract Study question There was a challenge to establishing haplotype for PGT in the family with de novo mutation because of the lack of information from affected members. Summary answer The ONT platform combined with MARSALA method can be used to perform PGT for DNM patients without the need for other samples as a reference. What is known already The proband was a 31-year-old female who was born with mental retardation and language delay. On physical examination, she was found to have distinctive Coffin-Lowry Syndrome features, such as distance between the eyes and low nasal bridge. However, the proband’s parents did not show any abnormalities. The couple underwent genetic counseling and whole-exome sequencing (WES). The results showed that a frameshift mutation (c.1496delG, p.Gly499Valfs*25) was identified in the RPS6KA3 gene, with a true mutation in the proband but no mutations in the parents. Study design, size, duration A couple requested genetic counseling at the reproductive center of Zhongshan Boai Hospital and underwent whole-exome sequencing (WES) in 2019. The proband then underwent PGT with Oxford Nanopore Technologies (ONT) and the MARSALA platform to block the transmission of the pathogenic mutation to her offspring in 2022. Participants/materials, setting, methods The proband underwent PGT to block the transmission of the pathogenic mutation to her offspring.We used long-read sequencing on the ONT platform to directly detect the mutation and nearby SNPs for construction of the haplotype in PGT. The MARSALA method was used to detect both the SNP-based haplotype and chromosome copy number variations in each blastocyst. Finally, a normal embryo was selected by comparison to the haplotype of the proband and transferred into the uterus. Main results and the role of chance Using WES, we found the novel, heterozygous, pathogenic c.1496delG (p.Gly499Valfs*25) mutation of the RPS6KA3 gene in the proband. The SNP-based haplotype that was linked to the pathogenic mutation site was successfully established in the proband, without the need for other family members to be tested with ONT. Eight blastocysts were biopsied to perform PGT and were assessed with a haplotype linkage analysis (30 SNP sites selected), to give results that were consistent with direct mutation detection using Sanger sequencing. The results of PGT showed that three of the eight blastocysts were normal, without the DNM. Moreover, the patient had a successful pregnancy, after transfer of a normal blastocyst into the uterus, and delivered a healthy baby. Limitations, reasons for caution This strategy has only been applied to one case and more cases with de novo mutaition are needed to prove the feasibility of this strategy for PGT-M. Wider implications of the findings This study is the first report of a de novo RPS6KA3 c.1496delG mutation in patient with CLS, which can expands the RPS6KA3 mutation spectrum and also provides a new strategy based on ONT and MARSALA to perform PGT-M with DNMs without the need for a pedigree sample as a reference. Trial registration number Not applicable

Failure to diagnose hypochondroplasia by prenatal diagnosis: a case report

BackgroundHypochondroplasia (HCH) is a common nonlethal skeletal dysplasia caused by pathogenic variations in the fibroblast growth factor receptor 3 (FGFR3) gene, and HCH has similar clinical manifestations with achondroplasia (ACH), which can be screened during the fetal period by prenatal ultrasound testing and diagnosed by genetic testing.Case presentationwe report the special case of a patient with obvious growth retardation and rhizomelic disproportionate short stature, accompanied by other manifestations, including an enlarged head and short hands at 1 year old. However, several multiple color ultrasound exams identified shortened limbs (< 3rd percentile), an increased biparietal diameter (> 95th percentile) and a low nasal bridge in the fetal period. Due to the high incidence rate of ACH, genetic testing for the hotspot FGFR3 gene c.1138 g > A pathogenic variations was performed immediately in the third trimester. Unfortunately, the definitive diagnosis could not be made before birth due to the negative result of hotspot gene exam. Whole exome sequencing (WES) was performed at 1 year identified FGFR3 gene c.1620C > A variations positivity, and the patient was finally diagnosed as HCH.ConclusionOur report extends the understanding of the limitations of prenatal genetic diagnostic testing, especially the hot spot pathogenic variations test should be not the only clinical diagnostic basis. Moreover, this case also emphasizes that further gene analysis for patients with significant conflict between the clinical manifestation and the prenatal genetic panel examination findings should be reconducted timely to spare the family from a delayed diagnosis or a misdiagnosis.

A rare case of lethal Raine syndrome presenting with facial dysmorphism and pyriform aperture stenosis

Raine syndrome is a very rare autosomal recessive disorder characterized by osteosclerosis, periosteal bone formation and distinct facial abnormalities that include microcephaly and low set ears osteosclerosis, cleft palate, gum hyperplasia, broad and depressed nasal bridge and proptosis. Patients affected with this syndrome have a mutation in FAM20C gene located on 7p22.3. This gene is responsible for phosphorylation of Serine residues on an enzyme casein kinase which helps in mineralisation of the bones.

Anesthetic management in a child with Coffin Siris syndrome.

Dear Editor, An 8-year-old boy with ARID1B-CSS Coffin Siris Syndrome (CSS) presented with left inguinal hernia for herniotomy. The child had an uneventful neonatal period but developed recurrent upper respiratory tract infection at 2 months of age requiring frequent hospitalization. He also developed an intellectual disability, hyperactivity, and seizure disorder. Evaluated as a floppy infant, genetic workup revealed ARID1B and SOX11 gene mutation associated with CSS. He had a hypoplastic fifth finger in his hands, bushy eyebrows, everted lips, coarse facies, hypertrichosis, hypotonia, micrognathia, macroglossia, and high arched palate [Figure 1].Figure 1: (a) Note bushy eyebrows, coarse facies, hypertrichosis, everted lips, macroglossia, low anterior hairline, prominent ears (b) Hypoplastic fifth finger (c) Airway secured with Size 2 i-GelOn examination, the child was anxious, aggressive, and distracted. He was premedicated with oral midazolam 30 min prior and induced with sevoflurane. After achieving end-tidal concentration of 2.5%, iv cannula was placed and airway secured with size-2 i-Gel. The patient was maintained with sevoflurane at MAC 1-1.2 and pressure support ventilation (PSV-Pro, GE Datex Ohmeda, Aspire View). No opioids or muscle relaxant was used. Ultrasound-guided ilioinguinal and iliohypogastric nerve block (IIN/IHN) was given. At the end of the surgery, i-Gel was removed deep after ascertaining adequacy of ventilation. The patient was observed for 24 h before discharge. CSS (OMIM 135900), first described by Coffin GS, is a rare genetic condition caused by mutations in the ARID1B gene with a prevalence of <1:100000 and equal male-female preponderance.[1,2] Known as “fifth digit syndrome,” CSS is characterized by moderate to severe intellectual disability, absent or hypoplastic terminal phalanx of the fifth digit, craniofacial abnormalities, coarse facies, hypertrichosis, hypotonia, short neck, irregular and protruding teeth, wide nose with low nasal bridge, macroglossia, micrognathia, and high arched palate.[2] These features lead to feeding difficulties, recurrent respiratory tract infections during infancy owing to micro-aspirations, and pose a risk of transient apnea/laryngospasm in the perioperative period. Combined with facial dysmorphism, these factors present a difficult airway scenario. Awake flexible fiber-optic intubation is the best approach but possible in compliant patients only. In our case, the child was uncooperative and aggressive due to mental retardation, and the surgery did not necessitate tracheal intubation. Therefore, we used supra-glottic airway (i-Gel) while preserving spontaneous respiration. Numerous case reports have described the genotypic and phenotypic profile of CSS; however, few have described anesthetic management of patients with CSS, the details of which are mentioned in Table 1.[3–5] Spinal abnormalities such as spina bifida, scoliosis, etc., have been associated with CSS. Although no such abnormalities were found in our patient, we did not contemplate neuraxial block in our patient as IIN/IHN has proven to be equal or more efficacious and safer than caudal/central neuraxial block. Moreover, opioid-free anesthesia led to a faster and smoother recovery.Table 1: Airway management Techniques reported in patients with CSSCSS is a rare congenital syndrome with distinct craniofacial anomalies and mental retardation presenting a challenging scenario to the anesthesiologist in the perioperative period. Detailed insight of the child’s condition, thorough preoperative workup, and difficult airway preparedness are essential. Supra-glottic airway device presents an important tool in the armamentarium of anesthesiologist and a viable and easy alternative to flexible fiber-optic intubation for successful management of such cases. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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.

Molybdenum cofactor deficiency caused by MOCS1 gene mutation: a case report

A boy attended the hospital at the age of 1 month due to left hand tremor for 1 week. A blood test showed a reduction in serum uric acid and a cranial MRI showed encephalomalacia, atrophy, and cystic changes. The boy had microcephalus, unusual facial features (long face, long forehead, protruded forehead, long philtrum, low nasal bridge, facial swelling, and thick lower lip), hypertonia of lower extremities, and severe global developmental delay. Whole-exome sequencing performed for the boy detected a homozygous mutation, c.217C > T(p.R73W), in the MOCS1 gene, which came from his parents and was determined as possibly pathogenic. The boy was diagnosed with molybdenum cofactor deficiency type A based on clinical manifestations and gene test results. This disease is reported for the first time in China.

Thanatophoric Dysplasia

Background: The term tanatophorik comes from the Greek word thanatophorus which means "innate death" or "bearing death". The problem that underlies this disease is the process of bone formation. This disease is associated with an autosomal dominant inherited mutation of the fibroblast growth factor 3 receptor (FGFR3) gene on the arm of chromosome 4 (4p16.3). Because FGFR3 is the main modulator in bone formation, the typical clinical features of this disease include shortening of the extremities, curved femur, clover-like skull and narrowing of the thoracic cavity.Tanatophoric dysplasia is a skeletal disorder that is "lethal" or deadly. The deaths occurred due to respiratory failure caused by reduced chest cavity capacity, hypoplastic lungs and / or brainstem compression.Destination: Reported a case of thanatophoric dysplasiaMethod: Case Report Case Report: Case 33 years old woman, with preterm parturient G1P0A0H0 35-36 weeks 1 latent phase + history of 2x laparotomy + suspected fetal tanatophoric dysplasia. On ultrasound examination, it was found that BPD = 9.14 cm; AC = 30.56 cm; HC = 32.05 cm; FL = 2.55 cm; AFI; 9.06cm; SDAU = 1.72 cm. The presence of frontal bosing, saddle nose and micromilia (proximal, distal, phalanges) was found. The patient was planned for vaginal delivery and the progress of labor was followed. Patients provided informed consent regarding the possibility of fetal death during labor and after birth. During the active phase of the labor process, hypotony uterine innersia occurs and oxytocin drip is performed to accelerate labor. The baby was born male, weight 2175 grams, body length 34 cm and A / S: 1/0. Postmortem physical examination revealed macroscopic findings of tanatophoric dysplasia infants such as hypertelorism, low nasal bridge, cranio-facial disproportion. Narrow chest with protruding abdomen and short, bent limbs.Conclusion: Tanatophoric dysplasia is "lethal" skeletal dysplasia. Careful prenatal examination is required in diagnosis and termination of pregnancy. Keywords: Thanatophoric dysplasia, prenatal diagnosis

VP04.17: Acitretin embryopathy due to acitretin intake during the first and second trimesters of pregnancy

Acitretin is an aromatic retinoid analog of vitamin A used to treat severe forms of psoriasis and disorders of keratinisation. It is contraindicated during pregnancy because of its teratogenic potential. Acitretin embryopathy is a rare teratogenic disorder due to acitretin exposure during the 1st trimester, with a risk of fetal malformations of nearly 20% involving the central nervous system, various craniofacial and ear abnormalities, as well as cardiac, upper and lower limbs defects. Only a few cases of newborns with exposure to acitretin in the 1st trimester and anomalies compatible with this syndrome are known. We describe the case of a 24-year-old woman with epidermolytic hyperkeratosis, taking daily acitretin 25mg for many years. Pregnancy was unplanned, discovered at 18 weeks of gestation and very poorly monitored. She missed several appointments and inadvertently maintained acitretin intake until 30 weeks of pregnancy. When referred to our consultation at 32 weeks a fetal scan was requested. Ultrasound at 34 and 36 weeks exposed craniofacial malformations including prominent frontal bone, abnormal ears, low-set ears, low nasal bridge and absent hand finger. Fetal echocardiogram was normal. A female neonate was delivered at term with 2,515g and an Apgar score of 9/10/10. Evaluation at birth confirmed craniofacial dysmorphism with microcephaly, craniosynostosis, sinking of metopic sutures with prominent frontal bone, low nasal bridge, microphthalmia, hypertelorism, low-set ears, high-arched palate and limb defects with elbow arthrogryposis, absent 1st finger in both hands and 4th and 5th finger foot syndactyly. Brain MRI showed no endocranial abnormalities. These findings are in accordance to the spectrum of defects described in the literature for acitretin embryopathy. This case emphasises the extreme precaution that is needed with the use of teratogenic drugs in women of childbearing age and the importance of mandatory use of an effective contraception.

Expert Consensus on Hyaluronic Acid Filler Facial Injection for Chinese Patients.

Beauty standards vary by race and region, which must be accounted for in creating beauty. Chinese have unique features, including a depressed nose, flat midface, and small chin, and have different cosmetic concerns. We performed a consensus study on filler injections based on the Chinese standard of beauty due to a lack of such study. We organized the YVOIRE Consensus Group, including 5 plastic surgeons. We discussed common problematic areas seen in Chinese and described techniques based on our experience with hyaluronic acid fillers, while considering peer-reviewed articles, followed by multiple consensus-developing sessions. Chinese faces are characterized by retruded forehead, chin, and low nasal bridge, with certain features believed to bring good fortune. Therefore, profiles of the forehead, nose, lip, and chin have substantial effects on attractiveness. The demand for cosmetic procedures is high among the young generation who particularly desire nose and chin augmentation. Attractive Chinese facial shapes are characterized by a long, slender facial shape and pointed chin. Lips are narrow and thick. When injecting fillers for Chinese, it is necessary to apply special methods that produce results consistent with these characteristics. Understanding the concept and demand of beauty depending on race and region is important. Patients should be evaluated before aesthetic procedures. Maintaining hygiene during the procedure is crucial. Moreover, methods for preventing pain are essential. Fillers should be injected into the correct anatomical site and layer to minimize side effects and maximize effectiveness.

Cytogenetic abnormalities and clinical presentation in down syndrome patients

Total 60 samples were received for karyotyping from patients of developmental delay, dysmorphism and mental retardation, of which 20 cases showed trisomy 21. There was an equal incidence in males and females. All neonates (20%) showed broad short neck and decreased muscle tone at birth. Most common feature in infants (50%) was depressed nasal bridge and slanting eyes. All children (30%) presented with developmental delay and mental retardation. Low set ears and depressed nasal bridge (80%) was the most common finding across all age groups. Most common CHD was VSD (20%). Robertsonian translocation involving 14q and 21q was seen in 15 % cases. One case presented with transient abnormal myelopoiesis at birth. One case presented with additional balanced t(10;18)

A Novel Pathological ARSB Mutation (c.870G>A; p.Trp290stop) in Mucopolysaccharidosis Type VI Patients

Mucopolysaccharidosis (MPS) type VI, also known as Maroteaux-Lamy syndrome, is a lysosomal storage disorder, characterized by the deficiency of the arylsulfatase B enzyme. The clinical phenotype and severity of the illness varies according to the residual enzyme activity. Typical features are a short stature, shortened trunk, protuberant abdomen, flexed-knee stance, arched back, corneal clouding, joint stiffness and contractures as well as a waddling gait. Patients typically have Hurler-like dysmorphic facial features: microcephaly, prominent forehead and eyes, a broad nose, low nasal bridge, thick lips, and hyperplastic gums with widely spaced teeth. Complications of the illness include obstructive airway, cardiac valvular problems, splenomegaly, hernias, and pneumonia. Unlike other MPS diseases, MPS VI is characterized by normal intellectual development. Since the disease is due to deficient glycosaminoglycan (mucopolysaccharide) metabolism, elevated urinary glycosaminoglycan levels are a main indicator of MPS. Diagnosis is confirmed by enzyme assays, specifically low arylsulfatase B activity in conjunction with the normal activity of other lysosomal enzymes. Enzyme replacement therapy and hematopoietic stem cell therapy are showing positive results in the management of the condition. The more severely affected patients, with a rapidly advancing form of the disease, have a short life span and succumb, most commonly to heart failure, by early adulthood. The frequency of ARSB variants in patients with MPS VI are as follows: 59.5% missense, 13.5% small deletions, 12% nonsense, 5% splice site or intronic variants, 3% small duplications, 3% large deletions, and 1% stop-loss. We report an Albanian family with siblings diagnosed with MPS Vl after clinical examination, biochemical tests, and molecular analysis. Hereby, a novel c.870G>A nonsense homozygous mutation was found responsible for the loss of the enzyme activity.

Checkmark rotation flap for nasal tip reconstruction in Asian patients

Background: Nasal tip reconstruction (NTR) of the Mohs defect is challenging, especially in Asians who have a relatively low nasal bridge and thin cartilages.Objective: To evaluate the usefulness of a new flap design, the checkmark rotation flap (CRF), for NTR in AsiansMethods and materials: We retrospectively reviewed 31 cases of NTR. Among these, 15 cases underwent CRF, which uses skin from the columellar or infra-tip area with a checkmark v-shaped incision (CRF group). The remaining 16 cases underwent reconstruction with other flaps such as the bilobed or island pedicle flap (Others group).Results: The average defect area was larger in the CRF than in the Others group (1.85 ± 1.01 cm2 vs. 1.10 ± 0.72 cm2, p = .0499), but the visual analog scale score was significantly higher in the CRF group (7.97 ± 1.36 vs. 6.25 ± 1.62, p = .0059). For complications, a depressed scar was observed in four cases (26.7%) in the CRF group; nine cases (56.3%) in the Others group presented with a depressed scar, hypertrophic scar, or scarring similar to a trap door deformity.Conclusion: CRF may be a favorable option for the reconstruction of intermediate-sized nasal tip defects, providing good cosmetic outcomes.

Limb Lengthening for Achondroplasia: Systematic Review and Meta-analysis

Achondroplasia is the most common genetic skeletal dysplasia. It is characterized by a rhizomelic form of dwarfism, exaggerated lumbar lordosis, a prominent forehead and a low nasal bridge. The trunk is generally of near normal length. The incidence of achondroplasia is approximately 1 in 25000 people.

Limb Lengthening for Achondroplasia: Systematic Review and Meta-analysis

Background: Achondroplasia is the most common genetic skeletal dysplasia. It is characterized by a rhizomelic form of dwarfism, exaggerated lumbar lordosis, a prominent forehead and a low nasal bridge. The trunk is generally of near normal length. The incidence of achondroplasia is approximately 1 in 25000 people. Objectives: In the present systematic review, we have aimed to synthesize evidence from the published literature about the safety and efficacy of limb lengthening in patients with achondroplasia. Also, we have aimed to assess which age is preferred to start the lengthening and effect of early management on natural growth and psychiatric health. Methods: An electronic search was conducted from the inception till September 2018 in Medline via PubMed. Data entry and processing were carried out using a standardized Excel sheet and reviewers extracted the data from the included studies. We performed all statistical analyses using Review Manager (RevMan) 5.3 for windows. Results: In the present study, 17 studies were included in the present systematic review and meta-analysis. In terms of gained length of femur, the overall effect estimate showed that limb lengthening procedure achieved a mean increase in femur length by 11.9 (95% CI 9.39 – 14.43) cm. In addition, the overall effect estimate showed that limb lengthening procedure achieved a healing index of femur 30.46 (95% CI 24.326 – 36.59) days/cm. Similarly, the overall effect estimate showed that limb lengthening procedure achieved a mean increase in tibia length by 9.5 (95% CI 8.169 – 10.927) cm. The overall effect estimate showed that limb lengthening procedure achieved a healing index of tibia of 32.09 (95% CI 18.65 – 25.52) days/cm Conclusion: It could be concluded that limb lengthening is a reliable procedure with a relatively low complication rate in increasing the length of femur and tibia in patients with achondroplasia.

A full-term infant with type II thanatophoric dysplasia

Abstract Objectives To report a neonate with clinical findings consistent with thanatophoric dysplasia (TD). Only a few cases of this rare and lethal skeletal disorder have been reported in South-East Asia. Case presentation A 37-year-old Asian female, fourth gravida at 39 weeks, presented to our hospital for an elective cesarean section due to polyhydramnios, frank breech and gestational hypertension. The father was a 42-year-old Asian male. There was no history of rashes, fever, alcohol intake, substance drug abuse, smoking habit or radiation exposure. Ultrasound (US) of 34-weeks’ gestation found a baby with frontal bossing, prominent temporal lobe, clover-skull and low nasal bridge. The thoracic diameter was smaller than the abdominal diameter. Short limbs without bowing were noted in femur and humeral bones. The patient delivered a baby boy, 4115 g, APGAR scores were 5 and 7 at 1 and 5 min. The baby had a dysmorphic face, frontal bossing, low nasal bridge, low-set ears and short neck. The thorax was narrow and abdomen was protuberant. The upper and lower proximal limbs appeared short. A chest X-ray revealed short, curved ribs and opacification of both lungs. He had respiratory distress shortly after birth and had persistent severe respiratory distress despite adequate mechanical ventilation. On the third day, he had cardiac arrest; resuscitation was not done due to family request. The baby was declared deceased due to cardiopulmonary failure related to his congenital anomaly. Conclusions Ultrasonography could readily indicate TD prenatally. The pregnancy can continue up to late third trimester without miscarriage. Most of the neonates die in utero; those who survive are dependent on ventilator.

Effectiveness of levator muscle resection combined with Mustarde's double Z-plasty for blepharophimosis-ptosis-epicanthus inversus syndrome

To investigate the effectiveness of levator muscle resection combined with Mustarde's double Z-plasty to correct blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). Between March 2015 and June 2017, one-stage operation of levator muscle resection combined with Mustarde's double Z-plasty were performed on 26 children with bilateral BPES. There were 16 boys and 10 girls with an average age of 7 years (range, 4-14 years). All patients marked the four typical signs of BPES. There were 7 cases accompanied with a low nasal bridge, and 20 cases with amblyopia and strabismus. The length of eye fissure was (19.5±4.5) mm, the width of eye fissure was (2.5±1.6) mm, the diameter of inner canthus was (42.1±6.5) mm, and the muscular strength of levator palpebrae superioris was (5.5±1.3) mm. All the incisions healed by first intention. Twenty-three patients were followed up 2-12 months, with an average of 10 months. Among which, 2 cases were less corrected, 3 cases were over corrected, 6 cases had poor curvature of the eyelid. No eyelid internal and external pronation or keratitis occurred. Amelioration of blepharoptosis and epicanthus was achieved in the other patients, and the double eyelid fold was naturally smooth. At 7 days after operation, the length of eye fissure was (27.2±1.9) mm, the width of eye fissure was (12.5±1.3) mm, and diameter of inner canthus was (29.4±2.6) mm, which were superior to preoperative values ( t=0.127, P=0.042; t=0.341, P=0.029; t=0.258, P=0.038). There was no angular deformity caused by the width and length regressions of eye fissures. The levator muscle resection combined with Mustarde's double Z-plasty can effectively correct BPES and obtain good effectiveness.

7p15 deletion as the cause of hand-foot-genital syndrome: a case report, literature review and proposal of a minimum region for this phenotype

BackgroundHand-foot-genital syndrome (HFGS) is a rare condition characterized by congenital malformations in the limbs and genitourinary tract. Generally, this syndrome occurs due to point mutations that cause loss of function of the HOXA13 gene, which is located on 7p15; however, there are some patients with HFGS caused by interstitial deletions in this region.Case presentationWe describe a pediatric Mexican patient who came to the Medical Genetics Department at the National Institute of Pediatrics because he presented with genital, hand and feet anomalies, facial dysmorphisms, and learning difficulties. Array CGH reported a 12.7 Mb deletion that includes HOXA13.ConclusionsWe compared our patient with cases of HFGS reported in the literature caused by a microdeletion; we found a minimum shared region in 7p15.2. By analyzing the phenotype in these patients, we suggest that microdeletions in this region should be investigated in all patients with clinical characteristics of HFGS who also present with dysplastic ears, mainly low-set implantation with a prominent antihelix, as well as a low nasal bridge and long philtrum.