A Novel NR0B1 Gene Mutation Causes Different Phenotypes in Two Male Patients with Congenital Adrenal Hypoplasia

X-linked congenital adrenal hypoplasia is characterised by the acute onset of primary adrenal insufficiency in infancy or early childhood and hypogonadotropic hypogonadism(HH)at puberty,arising from mutations of the nuclear receptor subfamily 0 group B member 1(NR0B1)gene.This study investigated an extended family with two affected males(patient A:23 years and patient B:2 months old)and three carrier females.Sequencing analysis of the NR0B1 gene coding region from the family revealed a novel hemizygous deletion[c.604delT;p.(C202Afs*62)]in the two male patients.Furthermore,the patients'respective mothers and their common grandmother had this heterozygous mutation,but it was not present in the Human Gene Mutation Database.The two male patients showed inconsistent clinical features at onset,particularly in early childhood;however,it is possible that the younger patient will eventually show a delay of puberty,feminisation,and nonspermatogenesis in adulthood,similar to that in the older patient.Identification of a novel NR0BI mutation in this family is important for the diagnosis and genetic counselling of children with primary adrenal insufficiency and HH,and will be helpful for predicting long-term clinical symptoms.

Isolated left ventricular apical hypoplasia:Systematic review and analysis of the 37 cases reported so far

BACKGROUND Isolated left ventricular apical hypoplasia(ILVAH),also known as truncated left ventricle(LV),is a very unusual cardiomyopathy.It is characterised by a truncated,spherical,and non-apex forming LV.The true apex is occupied by the right ventricle.Due to the rarity of the disease,just a few case reports and limited case series have been published in the field.AIM To analysing the so far 37 reported ILVAH cases worldwide.METHODS The electronic databases PubMed and Scopus were investigated from their establishment up to December 13,2022.RESULTS The majority of cases reported occurred in males(52.7%).Mean age at diagnosis was 26.1±19.6 years.More than a third of the patients were asymptomatic(35.1%).The most usual clinical presentation was breathlessness(40.5%).The most commonly detected electrocardiogram changes were T wave abnormalities(29.7%)and right axis deviation with poor R wave progression(24.3%).Atrial fibrillation/flutter was detected in 24.3%.Echocardiography was performed in 97.3%of cases and cardiac MRI in 91.9%of cases.Ejection fraction was reduced in more than a half of patients(56.7%).An associated congenital heart disease was found in 16.2%.Heart failure therapy was administered in 35.1%of patients.The outcome was favorable in the vast majority of patients,with just one death.CONCLUSION ILVAH is a multifaceted entity with a so far unpredictable course,ranging from benign until the elderly to sudden death during adolescence.

Classification of congenital thumb hypoplasia and deformity

Background:Congenital thumb deformities account for one-third or more of all cases of congenital hand deformity.However,the current classification schemes of congenital thumb hypoplasia are no longer adequate due to their lack of adaptability to increasing knowledge in the field.Hence,a modified system with the potential to adapt to ongoing advances in knowledge and understanding is desperately needed.Methods:Based on the photographs collected from thousands of cases of congenital deformities of the hand and upper limb over multiple decades in our department,we subdivided thumb hypoplasia according to the variables of morphological characteristics,anatomical structures,functional status,the relationship between thumb deformity and hand deformity,the relationship between congenital hand deformity syndrome and thumb hypoplasia,and the selection of treatment methods.Results:A total of 10 types were presented,which were elucidated with nomenclatures as well as pathological feature and symptoms.Conclusion:This modified system may shed additional light on the classification of congenital thumb anomalies,which will assist in a more effective selection of treatment modalities and offers significant benefits to both patients and practice.

Esophageal squamous papillomas with focal dermal hypoplasia and eosinophilic esophagitis

Focal dermal hypoplasia(FDH) is a rare disorder of the mesodermal and ectodermal tissues. Here we present an eight-year-old female known to have FDH who presents with poor weight gain and dysphagia. She was diagnosed with multiple esophageal papillomas and eosinophilic esophagitis. She was successfully treated with argon plasma coagulation and ingested fluticasone propionate, which has not been described previously in a child.

The Use of Transcatheter Laser Exposure in the Treatment of Cerebral Vessels Hypoplasia Accompanied by Migraine

The research is dedicated to the possibility of restoring cerebral blood supply in patients with brain vessels hypoplasia accompanied by migraine. The research involved 67 patients aged 29 - 58 (average age 42) with severe migraine. The examination plan included laboratory diagnostics, assessment of dementia severity (CDR), assessment of cognitive impairment (MMSE), cerebral computed tomography (CT), cerebral magnetic resonance imaging (MRI), cerebral scintigraphy (SG), rheoencephalography (REG), cerebral multi-gated angiography (MUGA). Hypoplasia symptoms were detected in 56 (83.58%) patients. To improve cerebral blood supply, the method of transcateter laser revascularization by means of low-energy CW lasers was used. Good immediate angiographic outcome manifested in persistent improvement of the intracranial vascular bed and marked collateral vascularization was obtained in 53 (94.64%) patients. Good clinical outcome— almost complete regression of migraine and vestibular disorders—was obtained in 49 (87.50%) patients. Satisfactory clinical outcome—partial regression of migraine and vestibular disorders— was observed in 7 (12.50%) patients. The method of transcatheter laser revascularization of cerebral vessels is a physiological, effective and low-invasive treatment for patients suffering from cerebral vessels hypoplasia accompanied by migraine. This method has virtually no alternative;it stimulates natural angiogenesis causing collateral and capillary vascularization steadily improving the blood supply of the brain. The effect obtained after the treatment persists for a long time (9 years and longer), it causes regression of migraine, reduces mental disorders, and can improve the patients’ quality of life.

Ipsilateral hemifacial microsomia with dextrocardia and pulmonary hypoplasia:A case report

BACKGROUND Hemifacial microsomia(HFM)is a rare congenital malformation characterized by a combination of various anomalies,including the face,ears,eyes,and vertebrae.Prenatal diagnosis for HFM is possible,and quite accurate ultrasound can detect obvious defects.The etiology is still unknown,although some hypotheses have been proposed,including gene mutation,chromosome anomaly,and environmental risk factors.However,there are few reports of pulmonary hypoplasia and dextrocardia in HFM.CASE SUMMARY A 2-year-old boy presented to the ear reconstruction department of our hospital complaining of deviation of the face to the right side and auricular anomaly.Physical examination revealed facial asymmetry,preauricular skin tags,and concha-type microtia with stricture of the external auditory canal on the right side.Head magnetic resonance imaging showed bilateral semicircular canal dysplasia and bilateral internal auditory canals stenosis.Audiometric examination showed bilateral severe sensorineural hearing loss.Chest radiography and computed tomography showed dextrocardia and right pulmonary hypoplasia.CONCLUSION This case presented a rare finding and an unusual association of 3 malformations,ipsilateral HFM,pulmonary agenesis,and dextrocardia.

Orthodontic-surgical treatment of an Angle Class Ⅱ malocclusion patient with mandibular hypoplasia and missing maxillary first molars: A case report

BACKGROUND Adult patients presenting with Angle Class II division 1 malocclusions that have a strong skeletal etiology can be challenging for clinicians,particularly if accompanied by retrognathia of the mandible and a dolichofacial growth pattern.CASE SUMMARY In this case report,we describe the successful orthodontic and surgical management of a 20-year-old woman with an Angle Class II malocclusion with a severe anteroposterior skeletal discrepancy characterized by mandibular deficiency.She had incompetent lips,dental and skeletal Class II malocclusion,high mandibular plane angle,mild mandibular crowding,and two missing maxillary first molars.The treatment plan comprised:(1)Extraction of two mandibular second premolars to decompensate and retract mandibular incisors;(2)pre-surgical alignment,leveling,and space closure of the teeth in both arches,and protraction of the second maxillary molars to close the maxillary space;(3)surgical treatment including a LeFort I osteotomy for maxillary retraction and rotation,a bilateral sagittal split osteotomy for mandibular advancement and rotation,and a genioplasty for correctting the skeletal deformities;and(4)post-surgical correction of the malocclusion.CONCLUSION The patient’s facial esthetics was significantly improved and a desirable occlusion was achieved after 16 mo treatment.Follow-up records after 2 years showed stable esthetics and function.

A protocol used to manage maxillary hypoplasia in cleft lip and palate patients

Objectives: We report our experience and the protocol we used in managing maxillary hypoplasia in cleft lip and palate patients. Patients and methods: 14 adult cleft lip and palate patients with maxillary hypoplasia were evaluated clinically. Dental models and radiographs including (lateral cephalograms and orthopantographs) were obtained at the initial visit and upon completion of the presurgical orthodontic treatment. Patients with occlusal discrepancies larger than 6 mm and severe palatal scaring underwent Distraction osteogenesis (DO) to advance the maxilla. Patients with an occlusal discrepancy of 6 mm or less, underwent traditional orthognathic surgery including le fort I advancement and Bilateral sagittal split osteotomy (BSSO) to seat the mandible in occlusion. Results: Five patients underwent orthognathic surgery. Two of them underwent double jaw surgery. Three underwent single jaw conventional le fort l advancement. Four patients required bone grafting to repair the residual alveolar defect and to augment the midface deficiency. Nine patients with severe maxillary hypoplasia underwent maxillary advancement using distraction osteogenesis. Conclusion: Patients with a severe maxillary hypoplasia of 6 mm or more and excessive palatal scaring are successfully treated with DO. Conventional le fort I is reserved for patients with less severe maxillary hypoplasia. Both techniques gave promising results providing having followed the proper selection criteria.

Central Brain Herniation Secondary to Influenza-Related Encephalopathy in a Pontocerebellar Hypoplasia Child: A Case Report and Review

Influenza-associated encephalopathy (IAE) can perform as varying patterns of neuroimaging. Central brain herniation (CBH) secondary to IAE is rare;it may be a bad prognosis. Here, we presented a 4-year-old girl with influenza who had a pontocerebellar hypoplasia (PCH) history;she performed the second Magnetic Resonance Imaging (MRI) on Day 6 from onset, showed the diffuse edema and the occurrence of central herniation;the medulla was “Z-like” folded and the basal cisterns were obliterated completely. Finally she was declared dead. The imbalance between supratentorial and infratentorial pressure can lead to the occurrence of CBH. Severe edema relates to IAE and unstable structure of the posterior fossa might be the main reason for the herniation. MRI is helpful in early diagnosis. Early treatment of cerebral edema in patients with congenital abnormalities of the posterior fossa is vital for their management.

Unilateral ovarian hypoplasia—A report of two cases

Unilateral ovarian hypoplasia is a rare event with unknown true incidence. Our knowledge about this developmental anomaly is limited and based primarily on case reports. Ovarian hypoplasia is usually asymptomatic;it is most commonly diagnosed from laparoscopy for other indications. Here we report two cases of unilateral ovarian hypoplasia in patients who presented to the Continuum Reproductive Center with primary infertility. After initial infertility workup, both patients underwent diagnostic laparoscopy for suspected tubal disease. In each case, operative findings were consistent with unilateral ovarian hypoplasia. Following the surgery, one patient underwent in vitro fertilization and achieved an ongoing pregnancy. The other conceived spontaneously, but was diagnosed with an ectopic pregnancy.

Pulmonary Hypoplasia: A Rare Cause of Chronic Cough in TB Endemic Area

Pulmonary hypoplasia is a rare disease characterized by a defect of lung development more often unilateral. The diagnosis requires several exams to eliminate other causes of pulmonary retraction. We report two cases at the department of pneumophtisiology of the University Teaching Hospital of Point G. The first case is a young adult who was complaining of a chronic cough. Etiological investigation required several exams including spirometry and Computed tomographic scan (CT scan). After elimination of all suspected causes of pulmonary opacity, the diagnosis of pulmonary hypoplasia was retained. The second case is a 2-year-old girl who was born with congenital cardiopathy whose respiratory complications were increasing during her childhood and respiratory explorations discovered pulmonary agenesis. Pulmonary hypoplasia is rare in our medical practice, but attention must be drawn to a retractile pulmonary opacity in young age after elimination of all infectious causes in TB endemic area.

Three Cases of Familial Clavicular Hypoplasia

CCD （cleidocranial dysplasia） is a kind of rare congenital skeletal dysplasia and deformity. It has rare clinical syndrome, such as forehead radius, small maxilla ofa cial, wide long distance eye, collapse nose, widening cranial suture, incompleted closure of the frontal, clavicle hypoplasia, increased range of shoulder motion and other abnormalities. Often accompanied by teeth hypoplasia or impacted, through a careful observation of the clinical morphology, case history and X-ray examination can confirm the diagnosis.

A rare clinical presentation of pulmonary hypoplasia

Pulmonary hypoplasia is a rare congenital anomaly, which is frequently associated with other congenital anomalies. Clinical symptoms vary depending on the other system anomalies and severity of pulmonary hypoplasia. Although it is usually diagnosed in infancy and childhood, some cases do not show any symptoms until the adolescent ages. In adolescents and adults with unilateral hypolucent lung, although it is seen rarely, pulmonary hypoplasia should always be kept in mind. In this article, we present a case with pulmonary hypoplasia who remained asymptomatic until puberty.

Biventricular isolated apical hypoplasia:First-time description of a new cardiac abnormality by multimodality imaging

Left ventricular isolated hypoplasia is a seldom-described cardiac abnormality.Right ventricular hypoplasia is usually associated with congenital anomalies of the pulmonary or the tricuspid valve,whereas biventricular isolated apical hypoplasia has never been described.We report the case of a 48-year-old man with no history of known cardiac disease who was found to have a complex cardiac abnormality characterized by:1)Deficiency of the myocardium within the biventricular apex with adipose tissue infiltration;2)Truncated right ventricle because of an absent trabecular portion of the inflow tract;3)Truncated and spherical left ventricular apex;4)Origin of the mitral papillary muscle in the flattened anterior left ventricular apex.Multimodality imaging was performed to delineate the morphological and functional characteristics of this cardiomyopathy fully.To the best of our knowledge,this is the first description of a new cardiac abnormality characterized by the hypoplasia of the apical region of both ventricles in the absence of valvular or coronary artery disease.

Congenital Unilateral Hypoplasia of the Orbicularis Oris Muscle:A Rare Cause of Congenital Unilateral Upper Lip Palsy

Asymmetric facial appearance may originate from abnormalities of facial musculature or facial innervation. Congenital absence or hypoplasia of facial muscles has not been known except for the depressor anguli oris muscle. Even, congenital unilateral hypoplasia of the orbicularis oris muscle cause of unilateral upper lip palsy has not been reported in the literature up to day. In this report, we present a patient with congenital unilateral upper lip palsy although the facial nerve was normal.

Wall Imaging for Unilateral Intracranial Vertebral Artery Hypoplasia with Three-dimensional High-isotropic Resolution Magnetic Resonance Images

Background：There are few studies for evaluating wall characteristics of intracranial vertebral artery hypoplasia （VAH）.The aim of this study was to determine wall characteristics of VAH with three-dimensional volumetric isotropic turbo spin echo acquisition （3D VISTA） images and differentiate between acquired atherosclerotic stenosis and VAH.Methods：Thirty patients with suspicious VAH by luminograms were retrospectively enrolled between January 2014 and February 2015.The patients were classified as ＂acquired atherosclerotic stenosis＂ or ＂VAH＂ based on 3D VISTA images.The wall characteristics of VAH were assessed to determine the presence of atherosclerotic lesions,and the patients were classified into two subgroups （VAH with atherosclerosis and VAH with normal wall）.Wall characteristics of basilar arteries and vertebral arteries were also assessed.The clinical and wall characteristics were compared between the two groups.Results：Five of 30 patients with suspicious VAH were finally diagnosed as acquired atherosclerotic stenosis by 3D VISTA images.25 patients were finally diagnosed as VAH including 16 （64.00%） patients with atherosclerosis and 9 （36.00%） patients with normal wall.In the 16 patients with atherosclerosis,plaque was found in 9 patients,slight wall thickening in 6 patients,and thrombus and wall thickening in 1 patient.Compared with VAH patients with normal wall,VAH patients with atherosclerosis showed atherosclerotic basilar arteries and dominant vertebral arteries more frequently （P =0.000）.Conclusions：Three-dimensional VISTA images enable differentiation between the acquired atherosclerotic stenosis and VAH.VAH was also prone to atherosclerotic processes.

Reversed vascularized second metatarsal flap for reconstruction of Manske type ⅢB and Ⅳ thumb hypoplasia with reduced donor site morbidity

Background:The predominant method for Manske type ⅢB and Ⅳ thumb hypoplasia is pollicization.However,for those who are not willing to sacrifice the index finger,a method that could reconstruct a functionally capable and aesthetically acceptable thumb remains desirable.This study aimed to investigate and assess the functional and radiographic outcomes of utilizing a reversed vascularized second metatarsal composite flap for thumb reconstruction as a new alternative.Methods:From May 2014 to January 2017,15 patients with Manske type ⅢB or Ⅳ thumb hypoplasia who were admitted to the Department of Hand Surgery,Beijing Jishuitan Hospital were included in this study.An osteocutaneous flap containing a section of second metatarsal and its distal head was transferred in reversed position to reconstruct carpometacarpal joint.The donor site was reconstructed by a split half of the third metatarsal.Various functional reconstructions were commenced at second stage.The reconstructed thumbs were evaluated using the Kapandji score,pinch force,and the capacities of performing daily activities through a detailed questionnaire.Results:Among these 15 patients(seven type ⅢB and eight type Ⅳ),there were ten boys and five girls with median age of 4.2 years(range:2.0–7.0 years).There were seven right,three left,and five bilateral thumbs for whom only the right thumb received surgery.There were 14 metatarsal flaps survived(14/15).With an average follow-up of 19.2 months,the reconstructed thumbs had acceptable functional and aesthetic outcomes and the donor foot presented in decent appearance without signs of impaired function.All 15 children have improved the Kapandji score(from 0 to an average of 6.7),pinch force(from 0 to an average of 1.5 kg),with ability of grip and pen holding.X-ray indicated continuous bone growth.Patients and parents had good acceptance of the new thumb.Conclusions:Reconstruction of an unstable hypoplastic thumb(Manske type ⅢB and Ⅳ)with use of a vascularized metatarsal is an effective strategy.It offers an alternative solution for parents insisting on saving the thumb.

Coarctation of the Aorta with Aortic Arch Hypoplasia：Midterm Outcomes of Aortic Arch Reconstruction with Autologous Pulmonary Artery Patch

Background： Coarctation of the aorta （CoA） with aortic arch hypoplasia （AAH） is a relatively common congenital heart disease in clinical practice. Nonetheless, the corrective surgical technique for infants and children is a clinical problem that remains controversial. In this study, we sought to evaluate the surgical effects of aortic arch （AA） reconstruction with coarctation resection and aortoplasty with autologous pulmonary artery patch for infants and young children with CoA and AAH. Methods： Between January 2009 and December 2015, a total of 22 infants and young children with CoA and AAH who underwent coarctation resection and aortoplasty with autologous pulmonary artery patch were enrolled in this study. The median age of patients was 4.5 （Q1, Q3： 2.0, 14.0） months and the median body weight was 5.75 （Q1, Q3： 4.10, 9.38） kg. All patients were diagnosed with CoA and AAH, and concomitant cardiac anomalies were corrected in one stage. Perioperative and postoperative data were collected and analyzed using the paired sample t-test. Results： No perioperative deaths occurred. No residual obstruction was detected by echocardiography. The postoperative pressure difference across the repaired segment of CoA was 14.05 ± 4.26 mmHg （1 mmHg = 0.133 kPa）, which was smaller than the preoperative pressure difference （48.30 ± 15.73 mmHg; t = -10.119, P 〈 0.001）. The median follow-up time was 29.0 （Q1, Q3： 15.5, 57.3） months. There was no death during the follow-up period, and all patients experienced obvious clinical improvement. Only one child underwent subsequent aortic balloon angioplasty due to restenosis. Computed tomography angiography showed that the AA morphology was smooth, with no aortic aneurysm or angulation deformity. Conclusion： AA reconstruction with coarctation resection and aortoplasty with autologous pulmonary artery patch could effectively correct CoA with AAH, and the rate of reintervention for restenosis is low.

Clinical results of combined palliative procedures for cyanotic congenital heart defects with intractable hypoplasia of pulmonary arteries

Background Congenital heart defects with intractable hypoplasia of the pulmonary arteries without intercourse or with intercourse stenosis is unsuitable for surgical correction or regular palliative procedures. We reported our experience with combined palliative procedures for congenital heart defects with intractable hypoplasia pulmonary arteries. Methods From 2001 to 2012, a total of 41 patients with cyanotic congenital heart defects and intractable hypoplasia of the pulmonary arteries underwent surgical procedures. From among them, 31 patients had pulmonary atresia with ventricular septal defect （VSD） and the other 10 cases had complicated congenital heart defects with pulmonary stenosis. Different kinds of palliative procedures were performed according to the morphology of the right and left pulmonary arteries in every patient. If the pulmonary artery was well developed, a Glenn procedure was performed. A modified Blalock-Taussig shunt or modified Waterston shunt was performed if pulmonary arteries were hypoplastic. If the pulmonary arteries were severely hypoplastic, a Melbourne shunt was performed. Systemic pulmonary artery shunts were performed bilaterally in 25 cases. A systemic-pulmonary shunt was performed on one side and a Glenn procedure was performed contralaterally in 16 cases. Major aortopulmonary collateral arteries were unifocalized in six cases, ligated in two cases and interventionally embolized in two cases. There was one early death because of cardiac arrest and the hospital mortality was 2.4%. Results Five patients suffered from postoperative low cardiac output syndrome, three had perfusion of the lungs, and two pulmonary infections. Systemic pulmonary shunts were repeated after the original operation in three cases due to the occlusion of conduits. The mean follow-up time was 25 months. The pre- and the post-operation left pulmonary indices were （8.13±3.68） vs. （14.9±6.21） mm2/m2. The pre- and post-operation right pulmonary indices were （12.7±8.13） vs. （17.7±7.78） mm2/m2. The pre- and post-operational pulmonary indices were （20.87±9.43） vs. （32.6±11.7） mm2/m2. They were all significantly increased （P 〈0.001）. The diameter of the pulmonary artery increased after the modified Blalock-Taussig shunt （（5.51±0.94） mm2/m2 pre-operation vs. （7.01±1.97） mm2/m2 post-operation）, the modified Waterston shunt （（5.70±3.96） mm2/m2 pre-operation vs. （9.17±3.62） mm2/m2 post-operation） and the Melbourne shunt （（2.17±0.41） mm2/m2 pre-operation vs. （7.35±2.49） mm2/m2 post-operation） （all P 〈0.05）. Bilateral pulmonary arteries developed well as compared to their pre-operation development. Hemoglobin decreased from （194±27） to （174±24） g/L （P 〈0.05） and peripheral oxygen saturation increased from （65±11）% to （84±6）% （P 〈0.001 ）. During the follow-up of 27 to 49 months, ultimate complete repair was performed in four cases and one patient underwent a Glenn procedure. Conclusions The procedures should be considered on a case to case basis in patients having hypoplasia of the pulmonary arteries with cyanotic congenital heart defects. Combined palliative operations could be an adequate strategic treatment.

Clinical and molecular genetic analysis of a Chinese family with congenital X-linked adrenal hypoplasia caused by novel mutation 1268del A in the DAX-1 gene

Congenital X-linked adrenal hypoplasia （AHC） is a rare disease characterized by primary adrenal insufficiency before adolescence and by hypogonadotropic hypogonadism （HHG） during adolescence. In this paper, we present a Chinese family with AHC. Two brothers, misdiagnosed with adrenal insufficiency of unknown etiology at the age of 9, were correctly diagnosed with AHC when delayed puberty, HHG, and testicular defects were observed. We investigated the clinical features and identified the dosage-sensitive sex reversal AHC critical region of the X chromosome gene 1 （DAX-1） mutation in this kindred. Direct sequencing of the DAX-1 gene revealed that the two siblings have a novel mutation （1268delA） of which their mother is a heterozygous carrier. This mutation causes a frameshift and a premature stop codon at position 436, encoding a truncated protein. It is important to increase knowledge of the mutational spectrum in genes related to this disease, linking phenotype to genotype.