Showing papers on "Hypertelorism published in 2023"

Augmentation of bone morphogenetic protein signaling in cranial neural crest cells in mice deforms skull base due to premature fusion of intersphenoidal synchondrosis

Abstract: Craniofacial anomalies (CFAs) are a diverse group of disorders affecting the shapes of the face and the head. Malformation of the cranial base in humans leads CFAs, such as midfacial hypoplasia and craniosynostosis. These patients have significant burdens associated with breathing, speaking, and chewing. Invasive surgical intervention is the current primary option to correct these structural deficiencies. Understanding molecular cellular mechanism for craniofacial development would provide novel therapeutic options for CFAs. In this study, we found that enhanced bone morphogenetic protein (BMP) signaling in cranial neural crest cells (NCCs) (P0‐Cre;caBmpr1a mice) causes premature fusion of intersphenoid synchondrosis (ISS) resulting in leading to short snouts and hypertelorism. Histological analyses revealed reduction of proliferation and higher cell death in ISS at postnatal day 3. We demonstrated to prevent the premature fusion of ISS in P0‐Cre;caBmpr1a mice by injecting a p53 inhibitor Pifithrin‐α to the pregnant mother from E15.5 to E18.5, resulting in rescue from short snouts and hypertelorism. We further demonstrated to prevent premature fusion of cranial sutures in P0‐Cre;caBmpr1a mice by injecting Pifithrin‐α through E8.5 to E18.5. These results suggested that enhanced BMP‐p53‐induced cell death in cranial NCCs causes premature fusion of ISS and sutures in time‐dependent manner.

Surgical management of penoscrotal hypospadias in a child with Opitz G/BBB syndrome: a case report

Abstract: Opitz G/BBB syndrome is a rare condition characterized by three significant anomalies; hypertelorism, cleft lip and palate, and hypospadias. However, other anomalies may be associated. Herein, we report a 4-year-old child presented with penoscrotal hypospadias. On examination, hypertelorism and cleft lip and palate were noticed, suggesting a diagnosis of Opitz G/BBB syndrome. The cleft lip was corrected in the first year, and a two-staged surgical approach was implemented for penoscrotal hypospadias. In the first stage, the chordee was corrected and urethral plate was reconstructed using a tabularized incised plate urethroplasty and testicular tunica vaginalis flap. In the second stage, the remanent hypospadias was corrected, and the meatal opening reached its normal location. In conclusion, a two-staged surgical approach for the treatment of penoscrotal hypospadias associated with Opitz G/BBB syndrome may provide excellent outcomes in early-recognized cases. The urologist should pay attention to abnormal facial characteristics in patients with hypospadias.

A Second Family with Myhre Syndrome Caused by the Same Recurrent SMAD4 Pathogenic Variation (p.Arg496Cys)

Abstract: Introduction: Myhre syndrome (MS; OMIM #139210) is a rare connective tissue disorder presenting with cardiovascular, respiratory, gastrointestinal, and skeletal system findings. Fewer than 100 patients were reported until recently, and all molecularly confirmed cases had de novo heterozygous gain-of-function mutations in the SMAD4 gene. Dysregulation of the TGF-beta signaling pathway leads to axial and appendicular skeleton, connective tissue, cardiovascular system, and central nervous system abnormalities. Case Presentation: Two siblings, 12 and 9 years old, were referred to us because of intellectual disability, neurodevelopmental delay, and dysmorphic facial features. Physical examination revealed hypertelorism, strabismus, small mouth, prognathism, short neck, stiff skin, and brachydactyly. Discussion: With a clinical diagnosis of MS, the SMAD4 gene was analyzed via Sanger sequencing, and a heterozygous c.1486C>T (p.Arg496Cys) pathogenic variation was detected in both of the siblings. The segregation analysis revealed that the mutation was inherited from the father who displayed a milder phenotype. Among the 90 patients in the literature, one family was reported in which two siblings carried the same variation (p.Arg496Cys), inherited from the severely affected mother. We are reporting the second family which has three affected family members, a father and two children. We report this study to remind the clinicians to be aware of the parental transmission of SMAD4 variations and also evaluate the parents of the Myhre cases.

Presentation and Treatment of a Patient With Jacobs Syndrome and Metopic Craniosynostosis

Abstract: Jacobs syndrome is a rare trisomy (47, XYY) found in ~1 in 1000 male children associated with infertility, autism spectrum disorders, macrocephaly, hypertelorism, tall stature, and macroorchidism. Diagnosis is often delayed due to relatively subtle phenotypic changes. Craniosynostosis, a fusion of the cranial sutures, has been described in ~1 in 2000 live births, of which 25% are related to a diagnosed syndrome with the most common being Apert and Crouzon. Craniosynostosis does not have a known association with Jacobs syndrome and no prior cases have been reported. This case report seeks to describe the presentation and treatment of a patient with Jacobs syndrome and metopic craniosynostosis.

Clinical characterization of familial 1p36.3 microduplication

Abstract: Unlike the 1p36 microdeletion syndrome, which has been extensively described, 1p36.3 microduplications have rarely been reported. We report the two siblings of familial 1p36.3 microduplication, presenting with a severe global developmental delay, epilepsy, and a few dysmorphic features. They were referred to moderate-to-severe developmental delay (DD) and intellectual disability (ID). Both were considered eyelid myoclonus with absence of epilepsy (Jeavons syndrome). The EEG is characterized by widespread 2.5-3.5 Hz spikes and spike slow complex wave, eye closure sensitivity, and photosensitivity. The children has same dysmorphic features, including mild bitemporal narrowing and sloping forehead, sparse eyebrows, hypertelorism, ptosis, strabismus, infraorbital creases, wide nasal bridge with bulbous nasal tip, dystaxia, hallux valgus, and flat feet. Family exome sequencing revealed a maternally inherited 3.2-Mb microduplication of chromosomal band 1p36.3p36.2. However, DNA purified from blood samples of either parent did not find evidence for a microduplication of 1p36 in somatic tissue, indicating that such a mutation might be carried in the germline of the parents as gonadal mosaicism. No other family members of the affected siblings' parents were reported to be affected by the symptoms found.

A case of Crouzon syndrome with papilloedema and exotropia

Abstract: Early fusion of skull bones is the root cause of craniosynostosis. Nonsyndromic craniosynostosis affect only one suture of the skull while syndromic craniosynostosis affects multiple sutures and are associated with craniofacial dysmorphisms also abnormalities of extremities and other bony anomalies. 90% of cases are attributed to fibroblast growth factor gene 2 on chromosome 10p 25-q26, is responsible for more than. Crouzon syndrome is an autosomal dominant cause that constitutes 4.5% of craniosynostosis patients incidence of which is 0.16/10,000 population worldwide, most commonly involving coronal and frontosphenoidal suture. There is increased antero-posterior diameter of skull, hypoplasia of maxilla, and shallow orbits. Other features being brachycephaly, mid-face hypoplasia, and wider skull base anteriorly causing hypertelorism. Compensatory growth of uninvolved structure causes frontal bossing. Hydrocephalus, parrot beak-nose, hypoplasia of the maxilla, and high-arched palate is also noted. Relative proptosis is seen in most of the cases due to orbital hypoplasia. Ocular findings include vision impairment, strabismus, glaucoma, nystagmus, occasionally, corneal size abnormalities, keratoconus, corectopia, or aniridia. This case report is unique as it describes a 12 year old female of crouzon syndrome which presented with papilloedema and divergent squint which is rearely associated with this syndrome.

Craniofrontonasal dysplasia: A case report

Abstract: Craniofrontonasal dysplasia (CFND) is a rare congenital malformation, which has a wide array of symptoms that can vary drastically between patients. These include coronal synostosis with associated brachycephaly, hypertelorism, cleft lip and palate, and limb malformations, among others. The pleomorphic nature of the disease and numerous clinical decisions required for its management present a unique challenge to craniofacial surgeons when considering indications and timing for surgical intervention. In this report, we present the case of a patient with CFND, their surgical management, and discuss updates in principles of management of CFND.

Börjeson-Forssman-Lehmann syndrome: A case report.

Abstract: Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.

P52 digeorge syndrome: hypocalcemic paralysis and interventricular defect

Abstract: DiGeorge syndrome (DGS), known as "22q11.2 deletion syndrome" (22q11DS) (MIM#192430#188400), is caused by microdeletion of the long arm of chromosome 22 resulting in impaired development of the pharyngeal pouch. It is the most frequent chromosomal microdeletion syndrome with an estimated prevalence of 1 in 3 in 6,000 live births and approximately 1 in 1,000 fetuses. 22q11DS is the second leading chromosomal cause of congenital heart malformations, after trisomy 21. Patients with DGS may have developmental abnormalities of the craniofacial structures, parathyroid glands, thymus, and cardiac outflow tract. Doctors have been screening infants with conotruncal heart abnormalities for DGS since the late 1990s, before which the diagnosis was only clinical. A 48–year–old woman came to our attention for recurrent episodes of tetanus paresis, the worst in her youth, associated with a systolic murmur. Her face was characterized by hypertelorism, thin lips, micrognathia, and low–set ears associated with short stature. Blood chemistry tests showed hypocalcemia during the tetanic crisis, exacerbated also during blood pressure measurement (Trosseau‘s sign with obstetrician‘s hand). The electrocardiogram showed sinus rhythm, high QRS voltages and the presence of U wave in some precordial leads (Fig. 1). The echocardiographic examination showed a globular left ventricle with evidence of a subaortic interventricular defect (Fig.2). The patient was sent for genetic evaluation with subsequent evidence of 22q11.2 microdeletion (Di George syndrome) and placed on oral calcium treatment and cardiac surgery evaluation for possible correction of the congenital defect. At the same time, psychological support was guaranteed for adequate coping with the diagnosed disease. The presence of multiple stigmata in the same patient, such as typical facies, congenital heart defects and hypocalcemia, must raise the suspicion of syndromic involvement of the patient and consequent genetic evaluation oriented towards diagnosis and adequate counseling.

First female Korean child with Coffin-Lowry syndrome: a novel variant in RPS6KA3 diagnosed by exome sequencing and a literature review

Abstract: Coffin-Lowry syndrome (CLS, OMIM # 303600) is a rare X-linked disorder caused by mutations in <i>RPS6KA3</i>. CLS is characterized by facial dysmorphism, digit abnormalities, developmental delays, growth retardation, and progressive skeletal changes in male patients. Females with CLS are variably affected, complicating diagnosis. Here, we describe the clinical and molecular findings in a female Korean child with CLS and review the associated literature. A 5-year-old girl presented with short stature and developmental delays. She had a coarse facial appearance characterized by a prominent forehead, hypertelorism, thick lips, and hypodontia. She also had puffy tapering fingers and pectus excavatum. We performed exome sequencing and identified a novel, likely pathogenic, heterozygous variant, c.326_338delinsCTCGAGAC (p.Val109Alafs*10), in <i>RPS6KA3</i> (NM_004586.2). This is the first Korean female genetically diagnosed with CLS. In contrast to the delayed bone age reported in previous studies, our patient showed advanced bone age and central precocious puberty. CLS should be considered as a differential diagnosis of short stature, tapering fingers, and developmental delay. We suggest that molecular techniques can be a useful tool for diagnosis of rare disorders such as CLS because such conditions are not simple, and the associated spectrum of phenotypes can vary.

A Neonatal Patient Diagnosed with Chromosome 18p 11.1 Microdeletion Syndrome Presented with Trisomy 18Like Phenotype

Abstract: Microdeletion of the short arm of chromosome 18 is one of the most common chromosome deletion syndromes. Its estimated frequency is 1 in 50,000 live-born infants, with female prevalence over males. Around 150 cases have been described till now. The reported abnormalities include growth deficiency, hypotonia, microcephaly, dysmorphic facial features such as ptosis, epicanthal folds, hypertelorism and micrognathia, and relatively small hands and feet. Our patient was a full-term low birth weight (2150 gm) female newborn, showing cleft upper lip and palate (hard and soft palate), bilateral congenital Talipes Equinovarus with rocker bottom foot, microcephaly, atrial septal defect. She was initially conservatively managed with gavage feeding, then shifted into paladai feeding of expressed breast milk. A multidisciplinary approach was adopted due to various malformations and for the potential occurring complications. To our knowledge, this is the first case diagnosed during the neonatal period.

Novel mutation causing Zellweger syndrome

Abstract: Genetic conditions have varied presentations, and one of them is the association with multiple malformation syndrome (MMS), which has a high mortality rate in the immediate postnatal period. Here, we describe a neonate born with multiple anomalies—wide anterior and posterior fontanelle, metopic suture, flat nasal bridge, hypertelorism, low set dysplastic ears, corneal cloudiness, micrognathia, webbed neck, simian crease, undescended testis, hypospadias, congenital talipes equinovarus, hypoplastic inferior cerebellar vermis, poor reflexes, hypotonia and ventricular septal defect. There was a history of sibling death with similar malformations, pointing towards a genetic aetiology. Clinical exome sequencing yielded the diagnosis of Zellweger syndrome with a rare mutation in PEX-19 gene. Inherited metabolic syndromes frequently masquerade as malformations, but family history of an affected sibling and clinical suspicion aided diagnosis of the infant.

A Rare Case of Telecanthus-Hypospadias Syndrome in a Pediatric Patient

Abstract: Hypertelorism and hypospadias are the main characteristics of telecanthus-hypospadias syndrome; however, it can also include other midline structural anomalies, such as cleft lip and palate, cryptorchidism, congenital heart problem, laryngotracheal cleft, esophageal fistula, and irregular scrotum. Here, we describe an eight-year-old male who was brought to us for cleft lip repair, but upon evaluation, the other listed anomalies were discovered. He had hypertelorism, hypospadias, a ventricular septal defect, and a history of cryptorchidism. A multidisciplinary approach involved pediatricians, oral surgeons, cardiologists, and pediatric surgeons. The patient underwent surgery for first-stage hypospadias correction and was advised to follow up for additional surgery and maintenance procedures before being discharged. We wish to report this case with the aim to enlighten budding pediatricians and surgeons about this rare syndrome.

Primary sudden cardiac death prevention in hypertrophic cardiomyopathy resulted from LEOPARD Syndrome

Abstract: Leopard syndrome is an autosomal dominant inherited disease manifested by numerous cutaneous birthmarks, heart electrical conduction disorders, hypertelorism, pulmonary valve stenosis, deafness and hypertrophic cardiomyopathy. The disease may be accompanied by symptomatic ventricular tachycardia. In patients without the need for cardiac pacing and indications for a cardioverter-defibrillator (ICD) implantation, a completely subcutaneous system (S-ICD) may become an efficient option.

Chromosome 6p25 deletion syndrome: A case report and review of ophthalmic features

Abstract: The 6p25 deletion syndrome is a rare genetic disorder characterized by a wide spectrum of congenital anomalies. Ophthalmic abnormalities appear to be highly associated with the syndrome, although this relationship has not been well characterized to date. We conducted a systematic literature review to highlight the ocular features in patients with this deletion syndrome and describe a 7‐month‐old female who has a 6.07 MB 6p25.1p25.3 deletion and a 4.25 MB 17q25.3 duplication. Our patient presented with multiple congenital anomalies, including macrocephaly, frontal bossing, low set ears, tent‐shaped mouth, saddle nose, flat midface, and hearing impairment. Her ophthalmic features included proptosis, down‐slanting palpebral fissures, hypertelorism, nystagmus, bilateral posterior embryotoxon, and decentered and abnormally shaped pupils. A systematic review of the published cases with sufficient clinical eye descriptions included 63 cases with a confirmed 6p25 deletion. The most common eye findings observed were posterior embryotoxon, iris hypoplasia, corectopia, cornea opacity, and glaucoma.

Three-dimensional radiographic features of craniometaphyseal dysplasia—a comparative CBCT study

Abstract: Abstract Purpose Craniometaphyseal dysplasia (CMD) is a rare skeletal disorder that has progressive thickening and increased density of the craniofacial bones along with abnormal metaphyses of the long bones. Other features include a wide nasal bridge, paranasal bossing, hypertelorism, and an increase in the zygomatic width. We present a series of cases that showcase the three-dimensional radiographic features of this rare condition and compare it with an age and gender-matched controlled group using cone beam computed tomography (CBCT). Objective To evaluate the three-dimensional radiographic features of craniometaphyseal dysplasia (CMD). Materials and methods Retrospective analysis of CBCT scans of 7 patients who were diagnosed with the rare condition craniometaphyseal dysplasia was evaluated. Radiographic features of the craniofacial bones, the paranasal sinuses prominently maxillary, and frontal and sphenoid sinuses were evaluated. Skull bones were also evaluated, and the size and shape of the sella turcica and external auditory meatus were measured. Retained primary teeth and impactions were evaluated using a panoramic reformatted image. The type of occlusion and buccolingual dimensions of jaw bones were also assessed. Age and gender-matched control samples were used to measure the same features for comparing CMD patients to healthy controls. The quality of normal and syndromic patients’ cortical and trabecular bone was determined by measuring pixel intensity values (PIV) generated by CBCT scans. Results Cone beam CT images of patients with CMD were analyzed to evaluate cranial bones, their density, and any abnormalities associated with the sinuses and foramina. Patients with CMD had bones increased in size. A significant increase in the amount of bone formed was found in the inner table of the frontal and occipital bones. All seven patients with CMD had smaller foramina due to the deposition of sclerosed bone in the foramina of the skull base. The paranasal sinuses, prominently maxillary and frontal and sphenoid sinuses, were smaller than the age and gender-matched controls. The buccolingual dimensions of jawbones were increased. The maxillary and mandibular arch relationship ranged from class II to class III. The mean nasal bridge measurement for the CMD patients was 26.77 mm, while in the controls, the mean nasal bridge measurement was 19.48 mm. The mean measurements of the right and left orbits of CMD patients were 30.6 mm and 31.07 mm respectively, and the mean measurements of the right and left orbits of controls were 32.45 mm and 32.04 mm. Pixel intensity values (PIVs) representing density ranged between 100 and 1000 PIVs for cortical bone and between − 60 and 258 for trabecular bone suggesting a densely sclerotic texture, while in the control group patients, the PIVs for cortical bone were > 1000 and 150–300 for trabecular bone. Conclusion CMD patients had significantly larger bone widths, a lower density of the bone, and smaller sinuses compared to the control group.

Prenatal diagnosis of Simpson-Golabi-Behmel syndrome type 1 with an 814 kb Xq26.2 deletion with the initial presentation of a thick nuchal fold.

Abstract: Simpson–Golabi–Behmel syndrome type 1 (SGBS1) is a rare X-linked recessive disorder characterized by overgrowth and multiple anomalies. Most clinical diagnoses of SGBS1 are made postnatally. We present the case of a pregnant woman in whom the fetus presented with a thick nuchal fold 5.6 mm at 15 weeks of gestation, leading to the prenatal diagnosis of SGBS1 with Xq26.2 (133408101–134221889) deletion. We report the case of a 34-year-old pregnant woman with the initial presentation of fetal thick nuchal fold 5.6 mm at 15 weeks of gestation. Amniocentesis of the fetal karyotype revealed a normal 46, XY, and single nucleotide polymorphism array showed Xq26.2 (133408101–134221889) deletion. Prenatal ultrasound at 21 weeks of gestation revealed a thick nuchal fold, hepatomegaly, nephromegaly, congenital diaphragmatic hernia, hypospadias, and polyhydramnios. Fetal magnetic resonance imaging revealed hepatomegaly, nephromegaly, congenital diaphragmatic hernia, and right lung hypoplasia. The woman had her pregnancy terminated at 24 weeks of gestation. The proband had a general appearance of low-set ears, hypertelorism, a large tongue, and hypospadias and some unique findings on autopsy, including hepatomegaly, right hiatal hernia, liver extensive extramedullary hematopoiesis, kidney marked congestion, and focal hemorrhage. The main prenatal ultrasound findings that alert clinical doctors about the possible diagnosis of SGBS1 included macrosomia, polyhydramnios, organomegaly, renal malformations, congenital diaphragmatic hernia, and cardiac anomalies. Our case underscores the importance of fetal karyotyping combined with single nucleotide polymorphism array when a thick nuchal fold is found. Genetic counseling is essential in SGBS1, and prenatal testing or preimplantation testing for subsequent pregnancies is necessary to identify possible pathogenic variants.

A Case Report of Hypothyroidism in a Noonan Syndrome Patient: A Comprehensive Approach to Diagnosis and Management

Abstract: Introduction Noonan syndrome is a multisystem, genetic, developmental disorder occurring with the incidence of 1 case per 1000 to 1 case per 2500 live births in the United -States. The condition occurs either in a sporadic or autosomal dominant manner and affects both males and females equally. [1] Ullrich (1930) and Turner (1938) described females with a syndrome of short stature, sexual infantilism, and a pattern of characteristic minor anomalies like pterygium colli. This syndrome originally named Ullrich-Turner syndrome was later called Noonan syndrome. It was first reported by Kobylinski (1883), but it was first recognized as a unique entity in 1963 when Pediatrician and Heart specialist Jacqueline Noonan and Ehmke described a series of patients with unusual facies and multiple malformations, including congenital heart defects. The characteristic abnormalities resemble those in Turner syndrome, which only affects females and so Noonan syndrome was used to be called ”Male Turner syndrome”. This term is no longer used because Noonan syndrome can affect females also. Noonan syndrome is also called Webbed neck syndrome, Pseudo-Ullrich Turner syndrome, Female Pseudo-Turner syndrome, or Turner-like syndrome.[2]The condition is mainly characterized by facial dysmorphism, congenital heart defects, growth hormone deficiencies, webbed neck, wide space nipples, and musculoskeletal, renal, genital, and bleeding abnormalities. Mental retardation can also occur in about 25% of patients with Noonan syndrome. Facial abnormalities include hypertelorism, down-slanting eyes, webbed neck, eyelid abnormalities, and skin manifestations. Prenatally the presentation of Noonan syndrome is not unremarkable, however, some cases are often complicated by polyhydramnios, fetal edema, increased nuchal translucency, and cystic hygroma. [3,4,5]. Very little is known about the occurrence of hypothyroidism in patients with Noon syndrome, this case report highlights the concomitant occurrence of hypothyroidism in a patient with Noonan syndrome, and stresses that further research should be done to find the association of these two.Case presentation : A 15 -year-old female patient was presented to the outpatient department of a tertiary care hospital for bilateral eye puffiness, easy fatiguability, and generalized body weakness. The patient’s condition started 6 months back and it gradually worsened. On further inquiry, the patient has a history of constipation on and off which relieves with laxatives. The past medical history of the patient was significant for acute hepatitis A and COVID-19 infection 3 and 1 year back respectively. The patient was born through a normal vaginal delivery at the hospital and she was the 7th child of his parents. The medical record of the patient showed that all the developmental milestones were up to date, and the patient received all the childhood vaccination. Family history was not significant for congenital heart defects, mental retardation, short stature, or unusual facial features. She was 135 cm tall and had 32 kg weight with vital signs of blood pressure of 100/70 mm Hg, pulse rate of 65 beats per minute, and respiratory rate of 15 breaths per minute. Examination revealed pale conjunctive, down slanting eyes, hypertelorism, webbed neck, shield chest with wide space nipple as shown in Figure.1. Systemic examination was unremarkable except for decreased muscles power in both upper and lower limb with a positive Gower’s sign. The patient examination findings were suggestive of some congenital syndrome and initially both Turner’s and Noonan were suspected. Karyotyping was done which showed normal 46 XX chromosomes as shown in Figure.2 A diagnosis of Noonan syndrome was made based on the clinical features and chromosomal analysis. The patient was further evaluated for recurrent eye puffiness and easy fatiguability and the laboratory results revealed anemia, hypothyroidism, and increased creatinine kinase as shown in Table. 1. A nerve conduction test and electromyography of both the upper and lower limb were done for progressive weakness that was consistent with mild myopathy, without evidence of spontaneous activity, mainly affecting the proximal muscles. A final diagnosis of Noonan syndrome with hypothyroidism that led to proximal myopathy was made. The patient was further evaluated for cardiac, ophthalmologic, hearing, renal and genital, and coagulation abnormalities that were all normal. The patient and her parents were counseled about the condition, she was started on levothyroxine 50mg OD, cap Iron sulfate 1 cap daily for two months, and tablet opendrine and paracetamol 35/450 mg SOS for muscular pain and weakness. She was referred to a pediatric endocrinologist for growth and development assessment and was instructed to do close follow-up with repeat thyroid function tests in 6 weeks and coagulation profile and echocardiography when symptoms develop.

Prenatal Diagnosis of Gómez-López-Hernández Syndrome

Abstract: Introduction: Gómez-López-Hernández syndrome (GLHS), also known as cerebello-trigeminal-dermal dysplasia, is an extremely rare neurocutaneous disease, classically described by the triad of rhombencephalosynapsis (RES), bilateral focal alopecia, and trigeminal anesthesia. The clinical and radiographic spectrum of GLHS is now known to be broader, including craniofacial and supratentorial anomalies, as well as neurodevelopmental issues. Case Presentation: Here, we present a case of antenatally diagnosed GLHS with RES, hydrocephaly, and craniofacial anomalies identified on ultrasound (low-set ears with posterior rotation, hypertelorism, midface hypoplasia, micrognathia, and anteverted nares) which were confirmed by autopsy after termination of pregnancy at 23 weeks of gestation. Discussion: As no known genetic causes have been identified and the classical triad is not applicable to prenatal imaging, prenatal diagnosis of GLHS is based on neuroimaging and the identification of supporting features. In presence of an RES associated with craniofacial abnormalities in prenatal (brachycephaly, turricephaly, low-set ears, midface retrusion, micrognathia), GLHS should be considered as “possible” according to postnatal criteria.

Pfeiffer syndrome type ii : a genetically proven case

Abstract: Pfeiffer syndrome is a rare genetic disorder in western population .This condition is very rare in the Asian population. This syndrome was first described by Rudolf Pfeiffer in 1964. We are presenting here is a case of newborn with pfeiffer syndrome type II demonstrating a cloverleaf skull with craniosynostosis, hypertelorism, bilateral proptosis, low set ears, syndactyly, broad thumb broad great toe, elbow synostosis.

18F-FDG PET/CT and Whole-Body Bone Scan Findings in Gorlin–Goltz Syndrome

Abstract: Gorlin–Goltz syndrome (basal cell nevus syndromes) is an uncommon, autosomal dominant inherited disorder characterized by developing basal cell carcinomas from a young age. Other distinct clinical features include keratocystic odontogenic tumors, dyskeratotic palmar and plantar pitting, and skeletal abnormalities. Clinicopathological findings of the syndrome are very diverse, and many symptoms manifest during a certain period of life. We present the compelling whole-body bone scan and 18F-FDG PET/CT findings in a 32-year-old man with odontogenic keratocyst, early-onset basal cell carcinoma, multiple ectopic calcifications in extremities, calcified falx cerebri, spinal scoliosis, macrocephaly, and ocular hypertelorism.

Mysterious Bilateral Foot Pain in a Child With Crouzon Syndrome

Abstract: Crouzon syndrome (CS) is a rare autosomal dominant disorder that requires care from a multidisciplinary team and early surgical management to minimize complications. Despite the shared similarities across craniosynostoses, CS can be differentiated by the presence of normal bone development of the hands and feet and hypertelorism (large distance between the eyes). Other common features include midface hypoplasia, shallow orbits, ocular proptosis, and dental abnormalities including possible bifid uvula or V-shaped maxillary arch. In this report, we present a case of prolonged foot pain in a four-year and two-month-old boy with CS; we also engage in a brief review of the literature. The patient's physical exam and laboratory work were unremarkable on the initial presentation. Radiographic films showed signs of potential demineralization of bone tissue. He was prescribed calcium and vitamin D supplementation with complete resolution of his symptoms at the three-month follow-up visit.

A rare case of Coffin–Lowry syndrome accompanied by a copper-beaten skull appearance

Abstract: Coffin-Lowry syndrome (CLS), usually a result of loss-of-function mutations in the RPS6KA3 gene located at Xp22.2, is a very rare genetic condition. It is associated with different phenotypes, including dysmorphic facial features, neuro-developmental impairment, short stature, and skeletal deformities. Here we describe a four-year-old boy who had distinct clinical features of CLS: moderate mental and motor retardation, brachycephaly, microcephaly, hypertelorism, low-set and prominent ears, down- slanted palpebral fissures, a depressed nasal bridge with thick nasal alae and septum, a high-arched palate, widely spaced teeth, and retrognathia. Genetic analysis revealed a pathogenic variant in the RPS6KA3 gene, NM_004586.3: exon 22: c.2186G>A: (p.Arg729Gln). His healthy mother was a heterozygous carrier of the variant. In addition to the clinical findings, the patient’s X-ray revealed a very rare feature of a copper-beaten skull appearance. The link between CLS and a copper-beaten skull has never been reported before. This case demonstrates the variability in presentation of CLS and signifies the association of a rare radiographic finding of copper-beaten skull with CLS. Based on this case, we recommend screening skull radiographs at the clinic for copper-beaten skulls in patients with CLS.

Bilateral cryptophthalmos with overlapping features of Manitoba oculo-tricho-anal (MOTA) syndrome and Fraser syndrome 2

Abstract: A male baby with bilateral cryptophthalmos without eyebrows, distorted anterior hairline, bifid nasal tip, low-set ears, hypertelorism and low anorectal anomaly who was phenotypically diagnosed with Manitoba oculo-tricho-anal syndrome (mutation in FREM1 gene) had an overlapping genotypic diagnosis of autosomal recessive Fraser syndrome 2 because of the presence of a closely related mutation in FREM2. This heterozygous variant was likely to be sporadic. Another mutation was identified in the CEP85L gene indicating lissencephaly 10. This genetic condition has abnormal gyri pattern in the occiput area. This form of lissencephaly is characterised by phenotypic heterogeneity whereby some patients have only mild mental retardation, while others have a very complex clinical picture. In conclusion, this rare condition with the overlap of genetics between several conditions highlights the need for genetic testing even in an low middle income country (LMIC).

Neurofibromatosis-Noonan syndrome and growth deficiency in an Iranian girl due to a pathogenic variant in NF1 gene

Abstract: Abstract Background Mutations in NF1 gene could cause allelic disorders with clinical spectrum of Neurofibromatosis type 1 to Noonan syndrome. Here, a 7-year-old Iranian girl is described with Neurofibromatosis-Noonan syndrome due to a pathogenic variant in NF1 gene. Methods Clinical evaluations were performed along with genetic testing using whole exome sequencing (WES). The variant analysis including pathogenicity prediction was also done using bioinformatics tools. Results The chief compliant of the patient was short stature and lack of proper weight gain. Other symptoms were developmental delay, learning disability, inadequate speech skill, broad forehead, hypertelorism, and epicanthal folds, low set ears and webbed neck. A small deletion, c.4375-4377delGAA, was found in NF1 gene using WES. This variant was classified as pathogenic according to ACMG. Conclusions NF1 variants may show variable phenotypes among the patients; identifying such variants is helpful in therapeutic management of the disease. WES is considered as an appropriate test to diagnose Neurofibromatosis-Noonan syndrome.

Treatment of Facial Lentigines in an Adult Female Patient Suspected with Leopard Overlap Noonan Syndrome

Abstract: Lentigines are defined as multiple small pigmented macules measuring up to one centimeter and surrounded by normal-appearing skin, commonly caused by genetic factors. LEOPARD syndrome (LS) is an autosomal dominant distinguished by the presence of several lentigines, with specific phenotypic characteristics that resembles Noonan syndrome (NS). LS is likely to be underdiagnosed or misdiagnosed because many of its symptoms are minor and the accurate diagnosis may be overlooked. Therapy for lentigines are generally aimed at tackling aesthetic disfigurement and its subsequent psychological impacts. This case report aims to highlight the efficacy of 532-nanometer (nm) Q-switched (QS) Nd:YAG laser in treating lentigines in a 21-year-old woman with LS overlap NS. The patient initially came to seek treatment of her facial lentigines. However, some mild abnormalities such as ocular hypertelorism, left eye ptosis, and webbed neck were observed. Hormonal, cardiac, and pulmonary functions were within normal limit. Histopathological results supported the diagnosis of lentigo. The patient was given sunscreen and depigmenting agents and was instructed to apply the medications routinely. The patient then underwent two sessions of 532-nm QS Nd:YAG laser with a 3 mm spot size, 1 J/cm2 fluence, and a 1 Hz frequency. Objective clinical improvements were observed using spectrophotometer examination, there were no side effects found, and she was satisfied with the results. Dermatologists should play an integral role in establishing the diagnosis and management of systemic syndrome, manifesting specifically as dermatological symptoms. Lentigines in LS last throughout the patient's lifespan. Nd:YAG laser therapy can be effective in treating lentigines with long-lasting results. It plays a role in improving the patient's life quality, especially where the genetic disorder itself is a debilitating condition. The limitation of this case report was the lack of a genetic test, as the suspected diagnosis was made based on clinical symptoms.