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Achondroplasia is the most common autosomal dominant form of skeletal dysplasia and is caused by heterozygous mutations of the fibroblast growth factor receptor 3 (FGFR3) gene at region 4p16.3. This study highlights the data of achondroplasia cases, clinical spectrum, and their outcome from small cities and the region around Rajasthan. The data for analysis were collected retrospectively from genetic records of rare disease clinic in Rajasthan. Clinical profile, radiographic features, molecular test results, and outcome were collected. There were 15 cases, including eight males and seven females, in this cohort. All had facial hypoplasia, depressed nasal bridge, prominent forehead, and characteristic radiographic features. A total of 14 cases were sporadic and one case was inherited from the mother. Mutation analysis showed 13 out of 15 cases with the p.Gly380Arg mutation in the FGFR3 gene. Hydrocephalus was developed in three cases, required shunting in two cases.

Objective: To determine the frequency of clinical features and cytogenetic abnormalities in patients of down syndrome and correlation of cytogenetic abnormalities with clinical features. Study Design: Cross sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, from Feb 2017 to Feb 2018. Methodology: Total 163 patients with clinical suspicion of Down syndrome were selected by non-probability convenient sampling and diagnosis was confirmed by conventional cytogenetic analysis using Giemsa trypsin banding technique. Clinical features were assessed and frequency of different cytogenetic abnormalities were noted. Results: Out of total 163 patients, 96 (59%) were male and 67 (41%) were female. Median age of the patients was 11 months. Trisomy 21 was detected in 158 (96.9%), Robertsonian translocation in 4 (2.4%) and mosaicism in 01 (0.6%) patient. The predominant clinical features observed were slaunted with eyes, epicanthic folds, depressed nasal bridge and protruding tongue. Conclusion: Trisomy 21 is the most common cytogenetic abnormality observed in patients of down syndrome.

Odontogenic keratocysts (OKCs) may occur in two different forms, either as solitary (non syndromic OKCs) or as multiple OKCs (syndromic OKCs). Multiple OKCs are usually associated with Gorlin–Goltz syndrome with features like skin carcinomas and bifid ribs, eye, and neurologic abnormalities. We report a rare case of Gorlin–Goltz syndrome in a 35-year-old male patient who presented with a swelling in lower left back teeth region since 1 week. Apart from these, other findings observed in the patient were frontal bossing, depressed nasal bridge, ocular hypertelorism, prominent supra orbital ridge, and mild mandibular prognathism. On the basis of clinical and radiological evaluation, Enucleation was planned in all the three quadrants and histopathological evaluation revealed multiple OKC’s. Patient was followed-up multiple times for the duration of six months. This case report highlights the important findings and presentation of a rare case of Gorlin Goltz syndrome along with its review of literature. Keywords: Odontogenic keratocyst, Basal cell carcinoma, Bifid ribs, Gorlin Goltz Syndrome.

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

Background: Opsismodysplasia (OPSMD) is an extremely rare and severe autosomal recessive skeletal dysplasia that is under the category of severe spondylodysplastic dysplasia. It is characterized by delayed bone maturation, and affected patients are identified by a peculiar craniofacioskeletal dysmorphism in the form of wide anterior fontanelle, depressed nasal bridge, anteverted nares, and short limbs and feet. Radiologically, they are characterized by severe platyspondyly, squared metacarpals, delayed skeletal ossification, and metaphyseal cupping. Case Presentation: We present the clinical and radiological features of a 14-month-old boy with a homozygous, likely pathogenic variant in INPPL1 gene c.2627dup (p.Pro977Thrfs*7) consistent with the diagnosis of OPSMD. He also has dilated cardiomyopathy. Conclusion: OPSMD is an uncommon form of skeletal dysplasia that should be suspected in the context of short stature with characteristic radiological features. Up to now, no definitive therapeutic measures are available, and hence preventive measures are essential in the management of families with affected members.

Witteveen-Kolk syndrome is a rare genetic disorder characterized by intellectual disability, developmental delay and dysmorphic facial features including a long face with prominent forehead, depressed nasal bridge, long-smooth philtrum and malformed ears. Skeletal abnormalities, microcephaly and malformation of the brain are other findings. This syndrome is caused by mutations in the SIN3A gene or microdeletions encompassing this gene. The protein encoded by SIN3A gene plays a regulatory role in the control of various developmental processes, especially cortical expansion and maturation. To date, 17 patients have been reported in the medical literature. In this article, we reported a patient with Witteveen-Kolk syndrome who had a retrognathia as an unusually finding. To the best of our knowledge, this is the first patient of Witteveen-Kolk syndrome reported from Turkey.

Raine syndrome is a rare, often lethal autosomal recessive condition marked by congenital malformations that range in severity. Considering that several case reports of this syndrome describe cases of stillbirth or perinatal death, information about the clinical presentation and development of this condition in mild, non-lethal cases is lacking. With that in mind, in this case report, we describe the clinical, oro-dental, and skeletal findings of a 14-year-old Brazilian patient diagnosed with a mild form of non-lethal Raine syndrome. This patient has very mild facial dysmorphia, not displaying hypoplastic nose, micrognathia, low set ears or depressed nasal bridge, which is uncommon even in other mild, non-lethal cases of RS. Furthermore, this patient has bilateral brain calcifications and a series of oro-dental abnormalities, such as amelogenesis imperfecta and recurrent periodontal abcesses. Sanger sequencing of genomic DNA identified a homozygous missense variant c.1487C > T at exon 9 of FAM20C (NM_020223.4) in the patient. The patient’s mother carries the same variant but is heterozygous. This variant predicts a proline to leucine substitution in position 496 (p.P496L, NP_064608.2) previously reported, which allows for the phenotypic comparison between these cases. This way, this case report calls attention to how differently RS can appear, highlighting the importance of new non-lethal Raine syndrome case reports to help further determine the phenotypic spectrum of this condition.

This study is to present two Chinese siblings who were diagnosed with congenital disorders of glycosylation (CDG) IIb because of mannosyl-oligosaccharide glucosidase (MOGS) deficiency. The siblings visited our hospital due to “pulmonary infection”. Facial dysmorphism including long eyelashes, blepharophimosis, depressed nasal bridge, and high palate was noted. Head MRI of the elder sister showed increased signals on T1W1, bilateral frontal gyrus stenosis, and thin corpus callosum. Both cases presented progressive hepatomegaly and elevated hepatic enzymes. Low immunoglobulin was discovered in the siblings. Compound heterozygous variants of NM_006302:c.1239_1267dup,p.Asp414Leufs*17, c.544 G > A,p.Gly182Arg, and c.1698C > A,p.Asp566Glu in MOGS were identified. Structural modeling demonstrated that the mutations were pathogenic to MOGS. Our study enriched the genetic and phenotypic spectrum of MOGS-CDG, and for children with facial dysmorphism, postnatal dyspnea, seizures, motor developmental delay, hypotonia, and immunological or gastrointestinal dysfunction, this disease should be highly suspected.

Coumarins (warfarin, acenocoumarol, phenprocuomon) are well known agents that are prescribed for prevention of thromboembolic episodes in pregnant women who are on mechanical heart valves prosthesis. It acts as double edge sword as fetus is unnecessarily exposed to teratogenic effect of drug. Warfarin is well studied drug in terms of its tetratogenic dose, period of exposure, fetopathic effects. Acenocoumarol is well known teratogen but its effect and lethal dose on fetus is less reported. We report a neonate who was exposed to acenocoumarol throughout intra uterine life. Neonate showed all features of coumarin embryopathy (flat facial profile, depressed nasal bridge, short columella, skeletal stippling, short distal phalanges in hand) and cephalhaematoma in addition. We also summarised the clinical findings of all the cases reported so far of acenocoumarol embryopathy. Acenocoumarol has same teratogenic potential as of warfarin. Doses causing embryopathy remained unexplored field. Clinicians need to document properly so that scientific data can be generated as ethical issues arises in head to head trial of these drugs.

Management of naso-orbito-ethmoidal fractures is a very complex process that includes proper diagnosis, classification and management. The evident telecanthus and depressed nasal bridge present a highly unaesthetic combination that highlights the importance of medial canthus and its bony insertion. A multidisciplinary approach helps the patient recover from associated head, eye or nasal injuries. Severe injuries may need secondary correction later, and this judgement by the surgeon helps the patient understand the outcome that may not restore the pre-trauma state but replicate the hard and soft tissue architecture as close as possible. The chapter will deal with the key points regarding the clinical features and the management of naso-orbito-ethmoidal fractures.

Pathogenic variants in ZMYND11, which acts as a transcriptional repressor, have been associated with intellectual disability, behavioural abnormalities and seizures. Only 11 affected individuals have been reported to‐date, and the phenotype associated with pathogenic variants in this gene have not been fully defined.\ud \ud Here, we present 16 additional patients with predicted pathogenic heterozygous variants in ZMYND11, including four individuals from the same family, to further delineate and expand the genotypic and phenotypic spectrum of ZMYND11‐related syndromic intellectual disability. The associated phenotype includes developmental delay, particularly affecting speech, mild‐moderate intellectual disability, significant behavioural abnormalities, seizures, and hypotonia. There are subtle shared dysmorphic features, including prominent eyelashes and eyebrows, depressed nasal bridge with bulbous nasal tip, anteverted nares, thin vermilion of the upper lip and wide mouth. Novel features include brachydactyly and tooth enamel hypoplasia.\ud \ud Most identified variants are likely to result in premature truncation and/or nonsense mediated decay. Two ZMYND11 variants located in the final exon ‐ p.(Gln586*) (likely escaping nonsense‐mediated decay) and p.(Cys574Arg) ‐ are predicted to disrupt the MYND‐type zinc finger motif and likely interfere with binding to its interaction partners. Hence, the homogeneous phenotype likely results from a common mechanism of loss‐of‐function.

A 16-year-old male presented to our hospital with complaints of mild mental retardation, umbilical and bilateral inguinal hernias, distended abdomen, profound bilateral hearing loss and recent onset seizures. On physical examination, he had a short stature, thick rough skin, depressed nasal bridge

We present the case of a patient with the following diagnosis: 29 weeks pregnancy in evolution, fetal achondroplasia with orofacial manifestations: macrocephaly, domed forehead, depressed nasal bridge, maxillary hypoplasia and general manifestations: short fingers, swelling of the back of the hand, increased angle between the femoral head and the femoral shaft, dorsal swelling of the foot, micromelia. The diagnosis was established prenatally after an ultrasound complex investigation and confirmed postnatally. We emphasize the increasingly important current role of the prenatal ultrasound investigation in early diagnosis of congenital anomalies like fetal achondroplasia and in the correct multidisciplinary management of cases.

We report a 3.5 year old male child, first in order of birth of healthy consanguineous Egyptian parents with typical characteristics of Kabuki make-up syndrome. The patient had microcephaly, high arched sparse eyebrows, hypertelorism, long palpebral fissures with eversion of the lateral third of the lower eyelids, bilateral ptosis, long eyelashes, blue sclera, depressed nasal bridge, broad nose with everted nares, and low set small deformed ears, thin lips, low post hair line, short neck, persistent fingertip pads, dysplastic nails, hypermobile joints, pigmented nevus on the back, lateral side of right foot and right leg and mild hypertrichosis over the lower back. Our patient had also a non-functioning left kidney, multiple chalazions in upper eyelids, enlargement of the glans penis, which were not reported previously, and moderate mental retardation.Keywords: Kabuki make-up syndrome; Genitourinary anomalies; Hyperpigmentation; Mental retardation

Cleidocranial dysplasia is a rare syndrome that has as main clinical findings changes in bones of the neurocranium and viscerocranium, clavicular, and teeth, although it can affect other bones. Its etiology originates from a defect of the gene CBFA1 of chromosome 6 p21, whose function is the differentiation of osteoblasts. Evidence suggests that this gene also acts in the participation of odontoblasts differentiation. The main clinical alterations are short stature, enlarged head, prolonged retention of deciduous teeth, delayed eruption of permanents, and presence of innumerable supernumeraries. The objective of this study is to report the diagnosis of cleidocranial dysplasia in a 4-year-old female patient with light brown skin color in a family health unit. The main clinical findings were prominence of the frontal and parietal bosses, ocular hypertelorism, and depressed nasal bridge and shoulders with hypermobility. The imaging examinations showed clavicular hypoplasia and changes in tarsal bones without major abnormalities in facial radiograph.

Cleidocranial dysplasia (CCD) is an autosomal dominant disease, characterised by generalised skeletal dysplasia, which has an estimated incidence of 1 in 1 000 000.1 Despite being a rare genetic condition, CCD has significant anaesthetic implications due to abnormal anatomical features of the head, mouth, neck and spinal column. These features have an impact on both general and neuraxial anaesthetic techniques. Craniofacial abnormalities resulting from CCD often present as a large brachycephalic head, with mandibular prognathism and maxillary underdevelopment. A depressed nasal bridge and hypoplastic sinuses disrupt nasal breathing, predisposing to recurrent upper respiratory tract infections.2 Permanent delayed closure of fontanelles and cranial sutures affect the majority of patients and may have implications for patient positioning under anaesthesia. Up to 94% of patients with CCD have dental findings leading to overcrowding and malocclusion.3, 4 In addition, absent or hypoplastic clavicles, short ribs, narrow upper thoracic diameter or funnel-shaped chest may lead to respiratory insufficiency, which is important for the early post-operative period, especially after general anaesthesia.2

Michelin tire baby syndrome (MTBS) is a benign hamartomatous condition with ring-like lesions present on the limbs and trunk. MTBS is a rare genodermatosis. According to our search, only 20 cases have been reported. We present a case of a six-month-old female child, with complaints of fever and seizures. Since birth, she had asymptomatic multiple, asymmetric skin folds on all four limbs, resembling "Michelin Man" logo of the French tire manufacturer. She had microcephaly with characteristic round face hypertelorism, depressed nasal bridge, hypertrichosis with low set ears, a thin down-turned vermillion border of the upper lip, and a short neck. MRI was normal. Clinically, the diagnosis of MTBS was made. In addition, the parents were counseled about the self-limiting course of this disorder. MTBS itself might not be a single disorder but may manifest as a clinical finding associated with other disorders; therefore, a regular follow up of these patients is usually advised.

A pediatrician noted that a male newborn delivered at 36 6/7 weeks’ gestation had a depressed nasal bridge with a deep groove between the alae nasi and nasal tip, and a small nose. The images of this newborn are shown in Figs 1 and 2. Figure 1. Depressed nasal bridge with a deep groove between the alae nasi and nasal tip. Figure 2. Small nose on side profile view. ### Prenatal and Birth Histories

WOS: 000382992500008, PubMed ID: 27489468, 48,XXYY syndrome is a rare sex chromosome abnormality. Although some physical features are similar to Klinefelter syndrome(47,XXY), 48,XXYY is typically associated with different neuropsyhciatric symptoms and phenotypic findings. Approximately 100 cases with 48,XXYY have been reported to date. In this report, a patient who was diagnosed with 48,XXYY syndrome with clincal evaluation and cytogenetic analysis is presented. A 6-year old male patient was hospitalized due to recurrent respiratory tract infections, recurrent abdominal distention and dyspepsia. He was the first and only child of nonconsanguineous parents. He had a history of mild developmental retardation. In his history, it was learned that he received treatment for gastroesophageal reflux and his symptoms improved with treatment. On physical examination, his weight was found to be 31 kg (>97 centile) and his height was found to be 123 cm (90 centile). He had upslanted palpebral fissures, depressed nasal bridge, long philtrum, incomplete cleft lip and micrognathia. Clinodactilia was found in the fifth fingers in both hands and large big toes and adduction in the second and third toes were found in both feet. Karyotype analysis showed a chromosomal composition of 48,XXYY. The patient presented here is the second Turkish case of 48,XXYY syndrome.

Odontogenic keratocysts (OKCs) may occur in two different forms, either as solitary (nonsyndromic OKCs) or as multiple OKCs (syndromic OKCs). Multiple OKCs usually occur as one of the findings in Gorlin-Goltz syndrome with other features such as skin carcinomas and rib, eye, and neurologic abnormalities. We report a rare case of Gorlin-Goltz syndrome in a 20-year-old male patient who presented with a slow growing swelling on lower right and left back teeth region since 2 months. Apart from these, other findings were frontal bossing, depressed nasal bridge, ocular hypertelorism, prominent supra orbital ridge, and mild mandibular prognathism. Excision was done and microscopic study revealed OKC and the follow-up could not be carried out for the complete management. We also presented a review of its pathogenesis, criterion, and differences between syndromic and nonsyndromic OKCs and suggest to thoroughly examine any patient who presents with multiple OKCs to rule out syndromic variety.

A female newborn baby presented with the features of Rhizomelic chondrodysplasia Punctata (RCDP) characterized by rhizomalic shortening with contracture of lower extremities, ichthyosis, microcephaly, dysmorphic facial features including a depressed nasal bridge, hypoplastic midface, full cheeks & low set ear, breathing difficulties and anthropometric measures below the expected indexes for her age. The patient also presented congenital heart disease, a less common manifestation of the syndrome. Radiological features include epiphyseal stippling & Journal of Bangladesh College of Physicians and Surgeons Vol. 32, No. 3, July 2014 multiple calcification in the epiphyseal cartilage, metaphyseal flaring and clefts in vertebral bodies. It is a rare autosomal recessively inherited skeletal dysplasia. The prognosis is bad and death usually occurs within the first year of age. We report a case of neonatal RCDP which was diagnosed based on the typical clinical and radiological features.J Bangladesh Coll Phys Surg 2014; 32: 174-177

A 2-month-old boy was presented with widespread lateralized blue macules (nevus cesius), an extensive nevus flammeus, and large patches of cutis marmorata telangiectatica congenita. Moreover, he had macrocephaly, a coarse facial appearance with depressed nasal bridge, retinal abnormalities, septal defects of the heart, and obliteration of the left brachiocephalic vein and major veins of the left arm with pronounced collateralization. The multisystem disorder of this boy cannot be categorized within the present classification of distinct types of phacomatosis pigmentovascularis. Although some similar complex cases have previously been reported, it seems too early to give them a specific name. Rather, the present case should be included, so far, into the group of unclassifiable types of phacomatosis pigmentovascularis.

Known for its dental and clavicular abnormalities, cleidocranial dysplasia is a rare disorder of bones. The appearance of the patient often confirms the diagnosis: short stature; large head with pronounced frontal and parietal bossing; ocular hypertelorism; and broad base of the nose with a depressed nasal bridge. Gnathic and dental manifestations are distinctive and lead to the initial diagnosis. The patients often have a narrow, high-arched palate; prolonged retention of deciduous teeth, and delay or complete failure of eruption of permanent teeth; also present are supernumerary teeth. Two female patients, 25 and 21 years old, visited the stomatology clinic complaining about the presence of deciduous teeth. One presented with supernumeraries, an arched palate, and was characterized as brachycephalic. She reported delay in the closure of sutures. The other one had a prominent forehead. Panoramic radiographs were required. Both patients were diagnosed with cleidocranial dysplasia and referred for dental treatment.

Achondroplasia, most frequent form of dwarfism, is of special interest in the field of dentistry because of its craniofacial characteristics that includes relative macrocephaly, frontal prominence depressed nasal bridge, maxillary hypoplasia and dental malocclusion. The present paper reports a case of 30 years old male achondroplastic patient with review of the literature.

The bones of the skull are held together by fibrous joints called sutures. Premature fusion of these sutures leads to a pathologic condition called as craniosynostosis. Although at least 50 nuclear genes including FGFR2, TWIST1, TCF12, and SMAD6 were identified as causative of craniosynostosis; only 25% of the patients can be genetically diagnosed. Here, we report a 3-year-old Turkish Caucasian boy with sagittal craniosynostosis with a de novo loss-of-function mutation in exon 4 of the AXIN2 gene for the first time. The patient has frontal bossing, high anterior hair line, depressed nasal bridge, bilateral epicanthus and low set ears which are correlated with his scaphocephaly. As a negative regulator of the Wnt signaling pathway which is one of the key modulators of craniosynostosis syndrome, it has been shown in model organisms that Axin2 orchestrates the regulation of beta-catenin especially in the intramembranous ossification process. This clinical report adds value to the literature that AXIN2 gene mutations could be a potential cause in human calvarial malformations, especially for the sagittal synostosis.

A female infant is born precipitously via vaginal delivery after spontaneous rupture of membranes. The mother is a 24-year-old African American woman whose history includes 2 cesearean deliveries with no other medical concerns. The current pregnancy is complicated by limited prenatal care. The gestational age is unknown. The infant’s birthweight is 1,870 g, and her Ballard score is consistent with an estimated 32 weeks of gestation. In the delivery room, the neonate has a spontaneous cry but with frothy oral secretions and a low heart rate requiring positive pressure ventilation, intubation, and brief cardiopulmonary resuscitation. Apgar scores are 5 and 7 at 1 and 5 minutes, respectively. Physical examination is significant for extensive blistering of her face, neck, chest, and extremities. She is placed in a plastic bag for skin protection, thermoregulation, and reduction of insensible water losses. The patient is then transferred to the NICU, where mechanical ventilation is ordered and umbilical line placement is attempted. Admission examination reveals sloughing of oral mucosa as well as diffuse sloughing of perioral skin, right eyelid contraction, auricle skin denudation with hypoplastic and posteriorly rotated bilateral ears, and depressed nasal bridge (Fig 1). The extremities show congenital localized absence of skin (Fig 2), nail dystrophy, and muscle wasting (Fig 3). The skin is dressed with moisturizer and sterile dressing. Figure 1. Denudation of eyelid, ears, and perioral and oral mucosa with depressed nasal bridge. …

Cutis laxa type II (MIM 219200) is a rare congenital disorder, first described by Debre et al. in 1937. During the period from 1937 to 2008, there have been 34 (25 females and 9 males) well-documented published cases of this rare disorder. In 2009, I reported the thirty fifth case of this disorder and I also reviewed the previously published and thirty four well documented cases. A dysmorphic girl was referred at the age of Four years (early April 2016) because of skin abnormality and delayed speech. The girl had cutis laxa with redundant loose skin present from birth. This skin abnormality was evident on the limbs and abdomen. Dysmorphic facial feature included, broad and depressed nasal bridge, and the eyes were wide set with downslanting palpebral fissures. Examination of the cardiovascular system was normal except for the presence of a systolic murmur. Echocardiography revealed the presence of a small atrial septal defect. In this paper, I am reporting the 36th case of Cutis laxa (Debre type) which is the first case to be associated with atrial septal defect.

Relapsing polychondritis is a rare, severe, episodic and progressive inflammatory disorder of unknown aetiology and autoimmune pathogenesis, causing recurrent inflammation of involving cartilaginous structures, predominantly those of the ears, nose, and laryngotracheobronchial tree. Rarity of this disease, array of many possible presenting symptoms, lack of specific diagnostic investigation and episodic nature often causes significant delay in diagnosis. We are reporting a 55 year old woman presenting with recurrent episodes of pain, swelling, redness of nose, and both ear resulting in depressed nasal bridge and floppy pinna. Relapsing polychondritis was diagnosed and she was treated with systemic corticosteroid successfully.DOI: http://dx.doi.org/10.3329/jom.v15i1.19881 J Medicine 2014; 15: 80-83

Opsismodysplasia (OMIM258480) is a rare, autosomal recessive skeletal dysplasia with delayed bone maturation. It was first described in 1977 by Zonana et al. and named opsismodysplasia by Maroteaux et al. in 1984 [Maroteaux et al., 1982; Maroteaux et al., 1984]. The clinical features include micromelia with extremely short hands and feet, as well as facial dysmorphism including prominent eyebrows, large open fontanels, depressed nasal bridge, short anteverted nose and relatively long philtrum. Some patients were also reported as having severe renal phosphate wasting [Below et al., 2013]. The characteristic radiographic features include severe platyspondyly, shortened long bones with dramatically delayed epiphyseal ossification, and characteristic hands with markedly delayed carpal ossification, short squared metacarpals and phalanges, and metaphyseal cupping [Beemer and Kozlowski 1994; Cormier-Daire et al., 2003; Maroteaux et al., 1984; Santos and Saraiva 1995; Tyler et al., 1999; Zonana et al., 1977]. The mortality is highly variable, ranging from death secondary to respiratory failure during the first few years of life to survival into adulthood.

We describe a-2-year-old boy who presented with a neonatal history of thrombocytopenia associated with a constellation of limb malformations mimicking split hand/foot malformation with long bone deficiency (SHFLD) syndrome. Limb malformations consisted of unilateral monodactyly with radial aplasia, unilateral split foot and bilateral club foot. Tibial aplasia of one limb and tibial hypoplasia of the other limb were notable. Partial agenesis of the sacrum was additional skeletal malformation. Craniofacial features included dense thick scalp hair, narrow frontal area, thick eye-brows, deep-set eyes, depressed nasal bridge, and small overhanging nasal tip, full-cheeks, and large ears. Array-CGH showed duplication of the short arm of chromosome 17p13.3 in the boy and his father, respectively. The father was free from any skeletal abnormalities, though he shares similar craniofacial dysmorphic features like his son. In addition, a paternal sib (uncle of the proband) manifested a phenotype similar to that of the proband. To the best of our knowledge the overall phenotypic and genotypic characterizations were consistent but not completely compatible with the traditional type of TAR syndrome or with SHFLD syndrome. We report on what might be a novel variant of SHFLD associated with transient thrombocytopenia, dysmorphic facial features, and a constellation of bone malformations.

The orofacial characteristics of ectodermal dysplasia include anodontia or hypodontia, hypoplastic conical teeth, underdevelopment of the alveolar ridges, frontal bossing, a depressed nasal bridge, protruberant lips, and hypotrichosis. Patients with this disease often need complex prosthodontic treatment. The options for a definitive treatment plan may include fixed, removable, or implant-supported prostheses, singly or in combination. However, financial constraints and other priorities can prevent the patient from choosing the most desirable treatment. This clinical report describes the diagnosis and treatment of ectodermal dysplasia in a 33-year-old man. The treatment included endodontic, restorative and definitive removable partial dentures fabricated to establish an acceptable therapeutic occlusal vertical dimension.

PURPOSE: To present a case of Treacher Collins syndrome. METHODS: A 7 days-old girl child with eye and facial disfiguration since birth was examined and managed conservatively. RESULTS: The presenting symptom of the patient was eye and facial disfiguration .she had sunken appearance of the face, with abnormally wide fish like mouth (macrostomia), depressed nasal bridge, parrot beak nose, malar hypoplasia with an anti mongoloid slant with associated micrognathia, glossoptosis, and high arched palate with cleft palate. On ocular examination, there was notching of lower eyelid, downward slanting eyes, complete absence of lower eyelid lashes. The patient was managed conservatively with nutritional support through nasogastric tube feeding, parenteral antibiotics and eye drops. During discharge, necessary counseling was done with an advice to have a regular follow up for further treatment of hearing loss and reconstructive surgery of facial anomalies. CONCLUSION: We are reporting this case of Treacher Collins syndrome baby, with no family history

We report on a consanguineous Lebanese family in which two sibs had pre- and post-natal growth retardation, developmental delay, large anterior fontanel, prominent forehead, low-set ears, depressed nasal bridge, short nose, anteverted nares, increased nasal width, prominent abdomen, and short limbs. Radiographs disclosed the presence of wormian bones, platyspondyly, decreased interpedicular distance at the lumbar vertebrae, square iliac bones, horizontal acetabula, trident acetabula, hypoplastic ischia, partial agenesis of the sacrum, ribs with cupped ends, short long bones with abnormal modeling, slight widening of the distal femoral metaphyses, and delayed epiphyseal ossification. Both sibs had a severe cardiomegaly and died at around 24 months from a heart failure. Differential diagnosis suggests that this is a second family presenting a newly described early lethal chondrodysplasia first reported by [Megarbane et al. (2008); Am J Med Genet Part A 146A:2916–2919]. © 2014 Wiley Periodicals, Inc.

Background: Leprosy is primarily a disease of developmental countries. About 4 million people have or are disabled by leprosy. Eighty-six percent of leprosy patients reside in Southeast Asia and Brazil. India accounts for up to 70% of total cases. Aim: To evaluate the incidence of orofacial lesions in treated leprosy patients. Materials and Methods: Thirty treated leprosy patients were examined clinically and the percentage of orofacial lesions were evaluated. Results: On evaluating the orofacial lesions, incidence of hypopigmentation on face and oral mucosa were highest (63%) followed by depressed nasal bridge and fissured tongue (33%). The incidence of crenated tongue was seen to be the lowest (3.3%). Conclusion: Orofacial lesions in leprosy patients develop insidiously, generally are asymptomatic and are secondary to nasal changes. Oral lesions may contribute to the diagnosis of the disease and be attributed to involvement of Mycobacterium leprae.

Diagnostic exome sequencing yields a single genetic diagnosis in ∼30% of cases, and according to recent studies the prevalence of identifying two genetic conditions in a single individual range between 4.6% and 7%. We present a patient diagnosed with three different rare conditions, each explained by a pathogenic variant in a different gene. A 17-yr-old female was evaluated for a history of motor and speech delay, scoliosis, distinctive craniofacial features, and dry skin in the Department of Clinical Genomics at Mayo Clinic. Her distinctive features included prominent forehead, epicanthus, depressed nasal bridge, narrow mouth, prognathism, malar flattening, and oligodontia. Family history was notable for dry skin in her mother and missing teeth in the paternal grandmother. Previous diagnostic testing was unrevealing including biochemical testing, echocardiogram, abdominal ultrasound, and electroencephalogram. Previous genetic testing included a microarray-based comparative genomic hybridization that was reported normal. Three pathogenic loss-of-function heterozygous variants were identified by exome trio sequencing, each linked to different genetic conditions: SIN3A (Witteveen–Kolk syndrome), FLG (dermatitis), and EDAR (ectodermal dysplasia). Together, these three genetic alterations could explain the patient's overall phenotype. This patient demonstrates the importance of performing a thorough curation of exome data when presented with a complex phenotype. Although phenotypic variability can explain some of these situations, the hypothesis of multiple diseases coexisting in a single patient should never be disregarded completely.

Weissenbacher-Zweymuller syndrome is a very rare syndrome that comprises the association of PierreRobin sequence with rhizomelia and characteristic x-ray findings. We report the first case diagnosed in a Jordanian newborn. This male newborn presented with cleft palate, micrognathia, glossoptosis, depressed nasal bridge, upturned nose, low set ears and rhizomelia. Radiographically, there was dumbbell appearance of the long bones of the limbs and coronal clefts of the vertebrae.

CASE A 21-year-old woman in her second pregnancy was referred to our Maternal-Fetal Unit for abnormal fetal growth detected during a 23-week routine scan. Her husband was 29 years old and this baby was his first. There was neither consanguinity nor any family history of congenital anomalies. Fetal detailed ultrasound findings (Accuvix V10, Medison, Seoul, Korea) were cranial suture diastasis (Figure 1a), nasal bone hypoplasia (Figure 1b), cranial bones and clavicles hypomineralization (Figures 1b and c), maxillary hypoplasia (Figure 1d), cerebellar vermis hypoplasia (Figure 2a) and low-set ears (Figure 2b). With this prenatal information the first diagnosis proposal was cleidocranial dysplasia. Karyotype analysis was suggested but impossible to realize due to administrative red tape. In prenatal ultrasound follow-up an intrauterine growth restriction was identified. At 32 weeks new central nervous system findings were detected: hypoechoic frontal cortex images suggestive of bilateral porencephalic cysts (Figure 2c) and first cervical vertebra dysraphism with dura mater bulging (Figure 2d). At 35 weeks intrauterine growth restriction and Doppler evaluation defined cesarean section. A male baby of 1410 g and 44 cm height was born. Apgar score was 8 at 1min and 9 at 5min. Minor respiratory distress was solved with cephalic oxygen chamber. Anthropometric measurements were cephalic perimeter 29 cm (Po5), 44 cm height (P 10 to 25), inner canthal distance 1.6 cm (P 3), interpupillary distance 3 cm (Po3), outer canthal distance 4.6 cm (P 3 to 50), palpebral fissures 1.2 cm (Po3), labial intercommissure 1.8 cm (Po3), total ear length 2.4 cm (Po3), total hand length 6 cm (P 50 to 97) and middle finger length 2.5 cm (P 50 to 97); lower segment length 19.6 cm, upper segment length 24.4 cm and upper/lower segments ratio 1.24 (normal range 1.65 to 1.70); feet length 7 cm (P 50 to 75) and penis length 1.6 cm (Po3). Physical examination showed pseudohydrocephalus, hypotricosis, scalp collateral venous system visible, triangular face (Figure 3a), widened fontanelles, biparietal prominence, low-set ears, upper oblique palpebral fissure, depressed nasal bridge with beaked nose profile (Figure 3b). Labial commissures had a downward orientation; two central natal teeth were visible, micrognathia and thin neck were evident. The cardiac evaluation demonstrated a systolic murmur grade II/IV. External genitalia agreed with male condition except for bilateral criptorquidia. Limbs presented general hypotrophy and with imitated articular movements (Figure 3c). Hands and feet were longer than normal (Figure 3d and e). Reduced subcutaneous fat was evident. Neurological examination reported general hypertonic condition and poor suction. Echocardiogram showed persistent ductus arteriosus 2.4 mm with mild pulmonary hypertension, without cardiac structural anomalies. Transfontanellar scan demonstrated hypoechoic collection associated with bilateral frontal porencephalic cysts and a wider cisterna magna and a dysraphism of the first cervical vertebra with dura mater bulging. Axial computerized tomography reported hypodense lines suggestive of bilateral frontal porencephalic cysts. All these findings permite to conclude that this case correspond to the Wiedemann–Rautenstrauch syndrome (WRS; online mendelian inheritance in man: 264090) or neonatal progeroid syndrome. Neonatal respiratory distress was successfully resolved after 24 h. Indirect hiperbilirrubinemia was treated with phototherapy. The baby was discharged once adecuate suction level was reached 40 days after birth weighing 1925 g. At 3 weeks buttocks upper fat was evident.

Disruption of normal ciliary function results in a range of diseases collectively referred to as ciliopathies. Here we report a child with a phenotype that overlapped with Joubert, oral–facial–digital, and Pallister–Hall syndromes including brain, limb, and craniofacial anomalies. We performed exome-sequence analysis on a proband and both parents, filtered for putative causative variants, and Sanger-verified variants of interest. Identified variants in CLUAP1 were functionally analyzed in a Xenopus system to determine their effect on ciliary function. Two variants in CLUAP1 were identified through exome-sequence analysis, Chr16:g.3558407T>G, c.338T>G, p.(Met113Arg) and Chr16:g.3570011C>T, c.688C>T, p.(Arg230Ter). These variants were rare in the Exome Aggregation Consortium (ExAC) data set of 65,000 individuals (one and two occurrences, respectively). Transfection of mutant CLUAP1 constructs into Xenopus embryos showed reduced protein levels p.(Arg230Ter) and reduced intraflagellar transport p.(Met113Arg). The genetic data show that these variants are present in an affected child, are rare in the population, and result in reduced, but not absent, intraflagellar transport. We conclude that biallelic mutations in CLUAP1 resulted in this novel ciliopathy syndrome in the proband.

Neonatal diabetes and hypothyroidism (NDH) syndrome was first described in 2003 in a consanguineous Saudi Arabian family where two out of four siblings were reported to have presented with proportionate IUGR, neonatal non-autoimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by enlarged kidneys and multiple small cysts with deficient cortico-medullary junction differentiation and normal kidney function. There was minor facial dysmorphism (depressed nasal bridge, large anterior fontanelle, long philtrum) reported but no facial photographs were published. Mutations in the transcription factor GLI-similar 3 (GLIS3) gene in the original family and two other families were subsequently reported in 2006. All affected individuals had neonatal diabetes, congenital hypothyroidism but glaucoma and liver and kidney involvement were less consistent features. Detailed descriptions of the facial dysmorphism have not been reported previously. In this report, we describe the common facial dysmorphism consisting of bilateral low-set ears, depressed nasal bridge with overhanging columella, elongated, upslanted palpebral fissures, persistent long philtrum with a thin vermilion border of the upper lip in a cohort of seven patients with GLIS3 mutations and report the emergence of a distinct, probably recognizable facial gestalt in this group which evolves with age. © 2016 Wiley Periodicals, Inc.

A 22-year-old, female patient reported with complaint of poor esthetics. Her past medical, dental, personal as well as family histories were non-contributory. After performing thorough general and extra oral clinical examination under aseptic precautions, various orofacial abnormalities were noted down which included brachydactyly of a thumb and an index finger of upper extremities on right side [Table/Fig-1] and hypertelorism with frontal bossing and depressed nasal bridge [Table/Fig-2]. Intra oral examination revealed hyperplastic frenula [Table/Fig-3], high lingual frenal attachment with lobed tongue [Table/Fig-4], multiple supernumerary teeth and fused teeth [Table/Fig-5]. Moreover, radiographic investigations were done which showed supernumerary teeth, fusion of two teeth and alveolar clefts in OPG and IOPA [Table/Fig-6,​,7].7]. A hand and wrist radiograph showed defect in phalanges [Table/Fig-8]. Review of literature shows that the diagnosis is based on clinical findings [Table/Fig-9] [1]. There are total 13 types of Oro-Facial Digital Syndrome (OFDS) out of which clinical features of Type 1 and Type 2 must be ruled out properly.

We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12 (p12-pter) transmitted from a maternal reciprocal translocation 6;12. Genetic analysis of umbilical cord blood of a 27-year-old woman, gravida 4, para 1 at 35 weeks' gestation due to a tricuspid regurgitation and orbital hypertelorism by sonography revealed an unusual karyotype of 46, XY, der (6) t (6;12) (p24;p12) mat. The pregnancy was terminated at 37 gestational weeks. The proband postnatally displayed by dysmorphic features of a round flat face with prominent cheeks and high forehead, hypertelorism, a short nose, a broad and depressed nasal bridge, anteverted nares, a deformed philtrum, an open mouth, thin upper vermilion and broad everted lower lip, low-set ears and aural atresia, broad hands with simian creases, and a short neck. By anatomy, the fetal was found to have right artery catheter vagus, congenital cataract, no turbinate and external auditory canal. Through the karoytpye-phynotpye analysis on the present patient and a review of other reported cases, we believed that the case was the first report, which expanded the database of partial trisomy 12p, and was of benefit for future clinical genetic counseling. At the same time, this study supported the viewpoint that phenotypic variability depends on the type and extent of the associated partial monosomy.

Achondroplasia is the most common form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of dental interest because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control require special precautions during dental management. Craniofacial manifestations and considerations in dental management are presented in 11-year-old female patient with achondroplasia. Keyword: Achondroplasia

Background: Down syndrome (DS) is a common chromosomal disorder associated with congenital heart disease (CHD) which could lead to severe morbidity or mortality. Objective: To determine the frequency and spectrum of clinical features, CHD and other comorbidities in children with DS in a tertiary care centre in Nigeria. Method : Consecutive children with clinical features of DS were recruited. The frequency of clinical features and co-morbidities were noted. All the children had echocardiographic evaluation to identify those with CHD. Results : A total of 64 children was recruited of which 36 (56%) were male. Fifty one (80%) had CHD of which atrio-ventricular septal defect (AVSD) was the commonest, being found in 20 (39%) children. Common clinical features present were oblique eyes in 64 (100%), depressed nasal bridge in 60 (94%) low set ears in 53 (83%) and epicanthal folds in 50 (78%). Conclusions : Prevalence of CHD amongst DS children in this study was 80% with AVSD being the commonest. The most prevalent clinical features seen in these children were oblique eyes, epicanthal fold, depressed nasal bridge, low set ears, hypertelorism and hypotonia. Sri Lanka Journal of Child Health , 2018; 47 (1): 50-55