Epicanthus Research Articles

Three-Dimensional Z-Epicanthoplasty Retains the Depth of the Medial Canthus With Scars That Are Less Visible.

Traditional coronal Z-epicanthoplasty usually generates visible scars, and V-Y advancement or skin redraping can damage the normal shape of the lower eyelid. In addition, these methods usually lead to loss of the medial canthus depth, which is important for the natural appearance of East Asians. This report aims to describe a 3-dimensional Z-epicanthoplasty that can maintain the depth of the medial canthus with fewer visible scars. Patients who underwent 3-dimensional Z-epicanthoplasty from January 2016 to December 2019 were included. In our method, excess skin in the horizontal direction was first rotated to the vertical position and then turned inward from a coronal to a sagittal orientation to supplement the skin deficiency of the medial canthus in the sagittal orientation. The skin flap turned in the sagittal orientation and maintained the depth of the medial canthus and the natural appearance of the eye. In total, 138 patients were included, and the follow-up interval ranged from 6 to 36 months. After the surgery, the epicanthi were removed, and the shapes of the patients' eyes were significantly improved and appeared natural. The surgical scars were hidden in the sagittal orientation rather than in the coronal orientation, which cannot be seen easily. The depth of the medial canthus was well preserved without any lower eyelid destruction. Patients were satisfied with the natural appearance of the medial canthus. This method could not only correct the epicanthal fold effectively with scars that are less visible but also maintain the depth of the medial canthus and make the appearance of the eye look more natural.

A Novel Thunderbolt Z-Epicanthoplasty for Asians.

Although many epicanthoplasty techniques have been proposed, prominent hypertrophic scarring in the medial canthal region remains a problem. The aim of this study was to develop a novel design that has a less prominent scar with minimal tension. A total of 489 patients underwent thunderbolt Z-epicanthoplasty from July 2015 to April 2019, with or without blepharoplasty. A triangular myocutaneous flap was lifted from the upper part of the epicanthal fold. The surrounding area was dissected to remove the rigid connective tissue between the orbicularis muscle and the skin, which creates skin tension. A Z-shaped flap toward the inferomedial canthal portion was added to create space for the triangular flap to be transposed to change the straight incision into a curved zigzag incision (final scar in the shape of a "thunderbolt"), making the scar irregular and less conspicuous. Postoperatively, all patients were followed up for ≥ 12 months. Among the patients, epicanthus tarsalis (60.12%) and palpebralis (36.19%) were the commonest epicanthus types, followed by epicanthus supraciliaris (3.07%) and inversus (0.61%). The average preoperative intercanthal distance was 42.25 ± 1.66 mm. This distance decreased significantly to 37.14 ± 1.78 mm (average, 5.11 ± 0.21 mm; p = 0.036) at the 12-month postoperative follow-up. Mild cicatricial redness was observed in the medial canthal area in six patients (1.2%) during the early postoperative period. The redness diminished within 6 months postoperatively. All patients obtained natural and aesthetically pleasing results without prominent hypertrophic scarring or other complications in the medial canthal area. The thunderbolt Z-epicanthoplasty is safe and effective for treating medial epicanthal folds. It is potentially helpful in minimizing postoperative medial canthal scarring and can be applied to various types of epicanthal folds with long-lasting results. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Non-Surgical Aesthetic IV.

Health Supervision for Children and Adolescents With Down Syndrome.

Health Supervision for Children and Adolescents With Down Syndrome.

Fatal case of classic Potter’s syndrome: a case report

Potter’s syndrome is a rare complication of oligohydramnios, incidence varies from 1 in every 2,000 to 5,000 fetuses with an average of 1 in 4,000. It is reported in 0.2-0.4% of autopsies in dead new-born who die immediately after birth. Potter’s syndrome primarily affects male fetuses (2:1) and is characterized by pulmonary hypoplasia and renal failure. Here, we are presented a case of classic Potter’s syndrome with fatal outcome. The baby was a live preterm male, born to a 28 years old multigravida, out of a non-consanguineous marriage via caesarean section. There was absolutely no liquor at the time of delivery. The baby did not cry immediately after birth and required resuscitation followed by mechanical ventilation. Multiple congenital anomalies suggestive of Potter’s syndrome were noted including facial features such as low set ears with overturned helix, slanting eyes, redundant fold of skin beneath the cheeks, prominent epicanthal fold, receding chin, flattened broad ear, flat nasal bridge, parrot beak appearance of nose and triangular facies. Chest X-ray showed small volume lung fields suggestive of pulmonary hypoplasia, and both kidneys were absent on ultrasonography indicating bilateral renal agenesis. At 15 min of life, baby developed tachypnea and severe chest retractions and succumbed after 1 hour of birth due to respiratory insufficiency. This case report emphasizes upon the importance of regular antenatal check-ups in every patient as it picks up the suspicious cases, leading to further workup and diagnosis, resulting in a timely decision regarding management.

EP220: Expanding the phenotypic spectrum of COLEC10-related 3MC syndrome: A glimpse into COLEC10-related 3MC syndrome in the Ashkenazi Jewish population

3MC syndrome is a clinical entity comprising four rare autosomal recessive disorders: Carnevale, Mingarelli, Malpuech, and Michels syndromes, characterized by variable expression of facial dysmorphia, cleft lip/palate, postnatal growth deficiency, hearing loss, cognitive impairment, craniosynostosis, radioulnar synostosis, and genital and vesicorenal anomalies. 3MC syndrome was initially described to be associated with bi-allelic pathogenic variants in the COLEC11 and MASP1 genes. Recently, bi-allelic pathogenic variants in COLEC10 have been described to be associated with 3MC syndrome. Features of COLEC10-related 3MC syndrome included short stature, blepharoptosis and epicanthus inversus, cleft lip/palate, and skeletal anomalies of the digits. The proteins encoded by COLEC11, MASP1, and COLEC10 form an intricate protein network that is important in regulating the lectin complement pathway. Syndromic features seen in 3MC syndrome are thought to be due to disruption of the chemoattractant properties that influence neural crest cell (NCC) migration. We identified seven individuals from three families of Ashkenazi Jewish descent with homozygosity of the novel c.311G>T (p.Gly104Val) variant in the COLEC10 gene (NM_006438.3) and phenotype consistent with 3MC syndrome. Individuals were retrospectively identified through the Dor Yeshorim screening program based on their genotype of the c.311G>T (p.Gly104Val) variant. The carrier frequency was calculated based on 21,887 individuals of Jewish descent. Samples were obtained anonymously through the Dor Yeshorim screening program between March 2020 and March 2021. Molecular protein modeling was completed. COLEC10 amino acid sequence was obtained, and then predictive protein models from I-Tasser were generated. Using PyMOL Molecular Graphic System 2.3.4 the effect the p.Gly104Val substitution in the COLEC10 protein model was analyzed. Clinical characteristics of the seven identified individuals included variable features of bilateral cleft lip and palate, radioulnar synostosis, short stature, hearing loss, and congenital heart defects. Similar facial features included hypertelorism, ptosis, prominent forehead, semicircular eyebrows, periorbital fullness, and broad nose. All individuals had reported normal intelligence. Carrier screening for the c.311G>T (p.Gly104Val) variant identified 164 heterozygotes out of 16,497 individuals of Ashkenazi Jewish descent, giving a carrier frequency of 1 in 101 or 0.99%. There were no heterozygotes identified out of 3,097 individuals of Sephardic Jewish descent and there were 13 heterozygotes out of 2,293 individuals of mixed Ashkenazi and Sephardic Jewish descent. Molecular protein modeling showed that the p.Gly104Val substitution alters local conformation. We identified a novel variant in the COLEC10 gene likely representative of a founder variant in the Ashkenazi Jewish population. Homozygosity of this variant is associated with variable features of 3MC syndrome. Given the observed carrier frequency, the lower than expected number of affected individuals may be due to the extreme phenotypic variability that includes clinically undiagnosed and variable presentations of the syndrome, even within the same family. Molecular protein modeling suggested that the p.Gly104Val variant results in abnormal protein folding. Abnormal protein folding has previously been shown to affect the secretion of the COLEC10 protein, leading to abnormal NCC migration, resulting in the observed craniofacial and skeletal anomalies associated with 3MC syndrome. COLEC10-related 3MC syndrome should be considered in the differential diagnosis for individuals with short stature, radioulnar synostosis, cleft lip and palate, and characteristic facial features.

EP080: A rare case of mosaic trisomy 15 with chylothorax

eP080: A rare case of mosaic trisomy 15 with chylothorax

EP093: De novo interstitial deletion of chromosome 7p22.1p21.2: A case report

Partial monosomy of the short arm (p) of chromosome 7 is a rare chromosomal disorder associated with a variable phenotype, depending on the size and location of the deleted region. When the deletion involves the interstitial deletion of 7p22.1p21.2 region, literature review describes phenotypic features that include craniosynostosis, microcephaly, ocular hypotelorism or hypertelorism, downslanting palpebral fissures, epicanthal folds, dysplastic ears, depressed nasal bridge, and cleft palate. Abnormalities of the thumbs and feet have been described, and also cardiovascular, renal and genital anomalies.

Esquirol-Séguin-Down Syndrome Associated with Atrial Septal Defect plus Tricuspid Regurgitation

Background: Esquirol-Séguin-Down syndrome (Trisomy 21) was first described by Jean-Etienne Dominique Esquirol in 1838 and later by Edouard Séguin in 1846. Thereafter, in 1862, John Langdon Down, a British physician emphasized that the syndrome is a distinct form of mental retardation. Congenital cardiac defects are observed in more than one third of the patients with Esquirol-Séguin-Down syndrome, and in approximately 80% these cardiac defects are atrioventricular septal defect or ventricular septal defect with the former being more common. The association of Esquirol-Séguin-Down syndrome with atrial septal defect plus tricuspid regurgitation has been rarely reported. The aim of this paper is to report the rare association of Esquirol-Séguin-Down syndrome with atrial septal defect plus tricuspid regurgitation. Patients and methods: Two and half years old boy with Esquirol-Séguin-Down syndrome, developmental delay and abnormal echocardiography was studied, and the recent relevant literatures were reviewed. Results: Dysmorphic facial features included hypertelorism, oblique palpebral fissures, epicanthic folds, depressed nasal bridge and low set ears. Echocardiography showed atrial septal defect with tricuspid regurgitation. Conclusion: This paper reports the first case of Esquirol-Séguin-Down syndrome in Iraq associated with atrial septal defect plus tricuspid regurgitation.

Identification of a novel KAT6A variant in an infant presenting with facial dysmorphism and developmental delay: a case report and literature review

BackgroundArboleda-Tham syndrome (ARTHS), caused by a pathogenic variant of KAT6A, is an autosomal dominant inherited genetic disorder characterized by various degrees of developmental delay, dysmorphic facial appearance, cardiac anomalies, and gastrointestinal problems.Case presentationA baby presented multiple facial deformities including a high arched and cleft palate, with philtral ridge and vermilion indentation, a prominent nasal bridge, a thin upper lip, low-set ears, an epicanthal fold, and cardiac malformations. Whole exome sequencing (WES) revealed a heterozygous nonsense mutation in exon 8 of the KAT6A gene (c.1312C>T, p.[Arg438*]) at 2 months of age. After a diagnosis of ARTHS, an expressive language delay was observed during serial assessments of developmental milestones.ConclusionsIn this study, we describe a case with a novel KAT6A variant first identified in Korea. This case broadens the scope of clinical features of ARTHS and emphasizes that WES is necessary for early diagnosis in patients with dysmorphic facial appearances, developmental delay, and other congenital abnormalities.

Adjustable Medial Epicanthoplasty Using a Rotational Flap for Epiblepharon Repair.

This report aimed to introduce the new adjustable rotational skin flap for epicanthoplasty in combination with traditional epiblepharon repair by the modified Hotz procedure. This retrospective study involved 25 consecutive patients with superficial punctate keratitis secondary to epiblepharon complicated with epicanthal fold who underwent the combined surgery between 2019 and 2020. The mean patient age was 11.4 years in this study with a median follow-up was 8months (range, 3-12months). The rationale of the surgery was to release vertical tension of the eyelids by dissecting dense connective tissue beneath the epicanthal fold and to form a new medial canthus using a rotational skin flap supplied by the redundant the upper and/or lower eyelid skin excised during the epiblepharon repair. Postsurgical resolution ofsuperficial punctate keratitis and patient satisfaction was achieved in all patients. Additionally, there were no complications, and no revisional surgery was required in all patients for a median 8 months follow-up period. Utilizing a rotational skin flap during epiblepharon repair is a useful adjunct during epicanthoplasty surgery. This modification is well tolerated and allows for intraoperative adjustment, whereas minimizing scarring and allowing for improved tissue relaxation.

Searching chromosome mosaicisms in 45,X Turner syndrome: how relevant is it?

To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS). FISH and PCR were performed for the presence of chromosome mosaicism and Y-derived-material and genetic findings were correlated to clinical data. Thirty-one participants were enrolled: 18 (58%) had chromosome mosaicisms (FISH), Y-derived material was found in 2. Yet, SRY primer was found with PCR in only one of them and DYZ3 was not found. The most frequent clinical findings were short or webbed neck (81,82%), high-arched palate (78%), breast hypertelorism, e cubitus valgus and genu valgus (57.6%, both), short fourth metacarpals (46.9%), epicanthic folds (43.8%), shield chest (43.8%), lymphedema (37.5%), and low set ears (34.4%). Both patients with Y-derived-material had primary amenorrhea, dyslipidemia and reached the height of 150 cm despite not treated with recombinant growth hormone (GHr). One of them showed 26% of leukocytes with Y-derived material and few clinical findings. FISH techniques proved efficient in detecting chromosome mosaicisms and Y-derived material and searching in different tissues such as mouth cells is critical due to the possibility of tissue-specific mosaicism. Phenotypical variance in TS may be a signal of chromosome mosaicisms, especially with the presence of Y-derived material.

Phenotype and genetic variant analysis of seven pedigrees affected with blepharophimosis syndrome

To analyze the clinical manifestations and gene variants of patients with blepharophimosis, ptosis and epicanthus inversus syndrome (BPES). Clinical data of 7 pedigrees affected with BPES were collected, and genomic DNA was extracted from peripheral blood samples of the probands and their relatives. All exons of the FOXL2 gene were subjected to Sanger sequencing. Those with negative findings were further screened by targeted capture and next generation sequencing (NGS) and microarray analysis. Pathogenicity of candidate variants were predicted by search of PubMed and related databases, and the impact of the variants was interpreted by protein prediction software. Diagnosis was confirmed by clinical phenotype, medical history and mutation analysis. A pathogenic variant was identified in six of the 7 pedigrees, which included four known pathogenic variants and one novel FOXL2 c.299dupA variant. A heterozygous 3q22.3q23 deletion, which encompassed the FOXL2 gene, was identified in another pedigree.As predicted, the c.299dupA frameshift mutation of FOXL2 gene can lead to the premature termination of protein translation, which is pathogenic. A novel and 5 known pathogenic variants have been identified in six pedigrees affected with BPES by the combined Sanger sequencing, target capture NGS and microarray analysis. Above findings have enabled genetic counseling and prenatal diagnosis for these pedigrees.

Confrontment and solution to gonadotropin resistance and low oocyte retrieval in in vitro fertilization for type I BPES: a case series with review of literature

BackgroundFOXL2 mutations in human cause Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). While type II BPES solely features eyelid abnormality, type I BPES involves not only eyelid but also ovary, leading to primary ovarian insufficiency (POI) and female infertility. Current mainstream reproductive option for type I BPES is embryo or oocyte donation. Attempts on assisted reproductive technology (ART) aiming biological parenthood in this population were sparse and mostly unsuccessful.Case presentationTwo Chinese type I BPES patients with low anti-müllerian hormone (AMH) and elevated follicle stimulating hormone (FSH) presented with primary infertility in their early 30s. Genetic studies confirmed two heterozygous duplication mutations that were never reported previously in East Asian populations. They received in vitro fertilization (IVF) treatment and both exhibited resistance to gonadotropin and difficulty in retrieving oocytes in repeated cycles. Doubled to quadrupled total gonadotropin doses were required to awaken follicular response. Patient 1 delivered a baby girl with the same eyelid phenotype and patient 2 had ongoing live intrauterine pregnancy at the time of manuscript submission.ConclusionsThis is the second reported live birth of biological offspring in type I BPES patients, and first success using IVF techniques. It confirmed that ART is difficult but feasible in type I BPES. It further alerts clinicians and genetic counsellors to type female BPES patients with caution in view of the precious and potentially narrowed reproductive window.

Whole‐exome sequencing identified first homozygous frameshift variant in the COLEC10 gene in an Iranian patient causing 3MC syndrome type 3

Background3MC syndrome type 3 is an autosomal recessive disorder caused by mutations in the COLEC10 gene besides other genes like COLEC11 and MASP1. This disorder is characterized by facial dysmorphism, cleft lip and palate, postnatal growth deficiency, cognitive impairment, hearing loss, craniosynostosis, radioulnar synostosis, genital and vesicorenal anomalies, cardiac anomalies, caudal appendage, and umbilical hernia.MethodsIn the present study, whole‐exome sequencing was performed in order to identify disease causing variant in an Iranian 7‐year‐old affected girl with craniosynostosis, dolichocephaly, blepharoptosis, clinodactyly of the 5th finger, high myopia, long face, micrognathia, patent ductus arteriosus, downslanted palpebral fissures, telecanthus, and epicanthus inversus. Identified variant confirmation in the patient and segregation analysis in her family were performed using Sanger sequencing method.ResultsA novel homozygous frameshift deletion variant [NM_006438.5: c.128_129delCA; p.(Thr43AsnfsTer9)] was identified within the COLEC10 gene. Up to now, only three 3MC syndrome patients with mutations in the COLEC10 gene have been reported, and here, we report the fourth patient and the first homozygous frameshift variant.ConclusionOther genes and factors responsible for 3MC syndrome occurrence are remained to be discovered. We believe further investigation of the genes in the lectin complement pathway is needed to be done for the identification of other causes of this disease.

Surgical Results and Patient Satisfaction After A New Surgical Technique for Asian Medial Epicanthoplasty: A Modified Skin Redraping Method Using a Horizontal Point Incision and Staged 'Y-Shaped' Dog Ear Correction.

The double eyelid operation is the most common cosmetic procedure conducted in Asians. However, the epicanthal fold presents a conundrum that limits the cosmetic results of double eyelid surgery. Despite not being a pathologic condition, numerous procedures have been developed and introduced to address this issue, but these techniques have potential disadvantages that include an unnatural ciliary position of the lower lids and prominent scarring. A total of 156 patients who underwent a double eyelid operation with medial epicanthoplasty using the modified skin redraping method using a horizontal point incision and staged dog ear correction between 2015 and 2019 at our medical center were enrolled in the study. A single senior plastic surgeon performed all surgical procedures. The Patient-Reported Outcome Measures (PROM) questionnaire was used to obtain objective satisfaction scores, and patient satisfaction scores were obtained using some criteria. Of 147 patients, 8 (0.05) complained of visible scarring at the medial epicanthal and upper fold line region; there were only 2 (0.01%) epicanthal fold recurrences and 1.36% wound-related complications. The PROM scores and patient satisfaction scores showed a strong positive linear correlation according to linear regression analysis (P < 0.001). We performed double eyelidplasty with epicanthoplasty by using "a modified skin redraping method using a horizontal point incision and a staged 'Y-shaped' dog ear correction." Few complications were encountered, and almost all patients were satisfied with their surgical outcome as determined by the PROM questionnaire.

Potocki-Lupski Syndrome Dup17p11.2 in a Girl with Hypotonia and Early Behavioural Disturbances.

Potocki-Lupski syndrome (PTLS) is a contiguous gene syndrome caused by duplication of chromosome 17p11.2. PTLS is characterized by hypotonia, failure to thrive, congenital anomalies (particularly of the cardiovascular system), intellectual disability, and behavioural disturbances. The patient was a full-term baby girl, 2,750 grams at birth, delivered via an uncomplicated vaginal delivery with pronounced hypotonia at birth. Nevertheless, there was failure to thrive (weight 7.6 kg; 2.8 SD). Micrognathia, epicanthal skin folds, and megalocornea were noticeable. There was a harsh continuous systolic murmur, and the ultrasound of the heart revealed a persistent arteriosus duct which was surgically closed. At the age of 18 months, the girl could not sit without support, and she could not utter simple words. The girl is often moody, angry, and aggressive. She is hyperactive and unable to establish contacts with family members. A 17p12-p11.2 microduplication was identified via MLPA. Muscle hypotonia, congenital heart malformation, failure to thrive, developmental delay, behavioural disturbances (or autism spectrum disorder), and intellectual disability are early signs of PTLS. The presence of PTLS was proven by an MLPA analysis.

FOXL2 in adult-type granulosa cell tumour of the ovary: oncogene or tumour suppressor gene?

A recurrent mutation in FOXL2 (c.402C>G; p.C134W) is present in over 95% of adult-type granulosa cell tumours (AGCTs). In contrast, various loss-of-function mutations in FOXL2 lead to the development of blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). BPES is characterised by an eyelid malformation often accompanied with primary ovarian insufficiency. Two recent studies suggest that FOXL2 C402G is a gain- or change-of-function mutation with altered DNA-binding specificity. Another study proposes that FOXL2 C402G is selectively targeted for degradation, inducing somatic haploinsufficiency, suggesting its role as a tumour suppressor. The latter study relies on data indicative of an FOXL2 allelic imbalance in AGCTs. Here we present RNA-seq data as genetic evidence that no real allelic imbalance is observed at the transcriptomic level in AGCTs. Additionally, there is no loss of protein expression in tumours harbouring the mutated allele. These data and other features of this mutation compared to other oncogenes and tumour suppressor genes argue strongly against FOXL2 being a tumour suppressor in this context. Given the likelihood that FOXL2 C402G is oncogenic, targeting the variant protein or its downstream consequences is the most viable path forward to identifying an effective treatment for this cancer. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Síndrome da deleção 2q37.3 – A primeira descrição de achados orais, relato de caso

Introduction: The 2q37.3 deletion syndrome is a disorder caused by the microdeletion of a subband on chromosome 2, whose epidemiology is approximately 150 cases worldwide, and the prevalence of 1: 10000. Its characteristics are developmental delay, facial dysmorphia, musculoskeletal abnormalities, and increased risk of congenital diseases. The purpose is to present, for the first time in the literature, the oral and dental clinical findings associated with the syndrome. Case report: The main physical characteristics of the syndrome were identified during the physical examination: thin upper lip, prominent columella, and epicanthic folds. In the intraoral examination, dental characteristics were reported, which may be associated with the syndrome: accumulation of dental calculus, hypomineralization and hypoplasia, crossbite, open bite, agenesis, taurodontism, and dentigerous cyst. The dental treatment consisted of the application of behavior management techniques, hygiene and diet instruction, prophylaxis, supragingival scraping, topical fluoride application, and extraction of the lower second molar. This is the first report of oral characteristics of the 2q37.3 deletion syndrome, giving importance to the characteristics observed in this patient. Such findings will be useful in the characterization of the syndrome, which is extremely rare, and may contribute to the clinical diagnosis of these patients, in addition to subsidizing the dental treatment of other individuals. Conclusion: We present oral clinical findings such as hypomineralization and hypoplasia, crossed and an open bite, agenesis, taurodontism, and dentigerous cyst present in the patient with the syndrome and we suggest that the involved gene or its deletion may be responsible for such findings.

A Novel Forkhead Box L2 Missense Mutation, c.1068G>C, in a Chinese Family With Blepharophimosis/Ptosis/ Epicanthus Inversus Syndrome.

The aim of the study was to report a novel forkhead box L2 (FOXL2) missense mutation in a Chinese blepharophimosis/ ptosis/epicanthus inversus syndrome family. Three generations of the Chinese family with blepharophimosis/ptosis/epicanthus inversus syndrome were enrolled in this study. Blood samples from patients of this family were collected and then analyzed by whole-exome sequencing. Confocal microscopy was performed to detect the subcellular location of FOXL2. Transactivation studies were performed and verified with real time polymerase chain reaction. A novel mutation (c.1068G>C) located in the downstream of deoxyribonucleic acid-binding forkhead domain was identified. Confocal photos showed the novel mutation did not disturb FOXL2 function, and the mutant protein could still transactivate steroidogenic acute regulatory protein, a key regulator of primary ovarian failure (POF). Our study revealed a novel missense mutation (c.1068G>C) and expanded the spectrum of FOXL2 gene mutations.

AN OVERVIEW OF LESS KNOWN JACOBSEN SYNDROMEAN OVERVIEW OF LESS KNOWN JACOBSEN SYNDROME

Jacobsen syndrome is catastrophic in 1 out of every 5 cases, with children usually dying within the first 2 years of life due to heart complications. Jacobsen syndrome is a contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. The prevalence has been estimated at 1/100,000 births, with a female/male ratio 2:1. The most common clinical features include pre- and postnatal physical growth retardation, psychomotor retardation, and characteristic facial dysmorphism (skull deformities, hypertelorism, ptosis, coloboma, downslanting palpebral fissures, epicanthal folds, broad nasal bridge, short nose, v-shaped mouth, small ears, low set posteriorly rotated ears). Abnormal platelet function, thrombocytopenia or pancytopenia are usually present at birth. Patients commonly have malformations of the heart, kidney, gastrointestinal tract, genitalia, central nervous system and skeleton. Ocular, hearing, immunological and hormonal problems may be also present. The deletion size ranges from 07 to 20 Mb, with the proximal breakpoint within or telomeric to subband 11q 23.3 and the deletion extending usually to the telomere. The deletion is de novo in 85% of reported cases, and in 15% of cases it results from an unbalanced segregation of a familial balanced translocation or from other chromosome rearrangements. Diagnosis is based on clinical findings (intellectual deficit, facial dysmorphic features and thrombocytopenia) and confirmed by cytogenetics analysis.