Elongated Face Research Articles

Sexual dimorphism in the cranium and endocast of the eastern lowland gorillas (Gorilla beringei graueri)

Sexual dimorphism of the nervous system has been reported for a wide range of vertebrates. However, understanding of sexual dimorphism in primate cranial structures and soft tissues, and more particularly the brain, remains limited. In this study, we aimed to investigate the external and internal (i.e., endocast) cranial differences between male and female eastern lowland gorillas (Gorilla beringei graueri). We examined the differences in the size, shape, and disparity with the aim to compare how sexual dimorphism can impact these two structures distinctively, with a particular focus on the endocranium. To do so, we reconstructed gorilla external crania and endocasts from CT scans and used 3D geometric morphometric techniques combined with multivariate analyses to assess the cranial and endocranial differences between the sexes. Our results highlighted sexual dimorphism for the external cranium and endocast with regard to both size and shape. In particular, males display an elongated face accompanied by a pronounced sagittal crest and an elongated endocast along the rostroposterior axis, in contrast to females who are identified by a more rounded brain case and endocast. Males also show a significantly larger external cranium and endocast size than females. In addition, we described important differences for the posterior cranial fossae (i.e., the position of the cerebellum within the brain case) and olfactory bulb between the two sexes. Particularly, our results highlighted that, relatively to males, females have larger posterior cranial fossae, whereas males have been characterized by a larger and rostrally oriented olfactory bulb.

The incidence and clinical characteristics of fragile X syndrome in China.

Fragile X syndrome (FXS) is a X-linked neurodevelopmental disorder (NDD). This study aims to investigate the incidence of FXS in Chinese children and analyze the comprehensive clinical characteristics of these FXS children. Children diagnosed with idiopathic NDD were recruited between 2016 and 2021 from the department of Child Health Care, Children's Hospital of Fudan University. We combined tetraplet-primed PCR-capillary electrophoresis and whole exome sequencing (WES)/panel or array-based comparative genomic hybridization (array-CGH) to identify the size of the CGG repeats and the mutations or copy number variations (CNVs) in the genome and in FMR1. The clinical features of FXS children were analyzed according to pediatricians' recording, parental questionnaires, the results of examinations and follow-up. The incidence of FXS in Chinese children with idiopathic NDD was 2.4% (42/1753) and in those with FXS, 2.38% had a deletion (1/42). Here, we present the clinical characteristics of 36 children with FXS. Overweight was observed in two boys. The average intelligence quotient (IQ)/development quotient (DQ) of all FXS patients was 48. The average ages of meaningful words and walking alone were 2 years and 10 months and 1 year and 7 months, respectively. The most frequent repetitive behavior was stimulated by hyperarousal to sensory stimulation. On social aspects, social withdrawal, social anxiety, and shyness accounted for 75%, 58%, and 56% of the total number of children, respectively. Approximately 60% of FXS children in this cohort were emotionally labile and prone to temper tantrums. Self-injury and aggression toward others could also be observed, at 19% and 28%, respectively. The most frequent behavioral problem was attention-deficit hyperactivity disorder (ADHD) seen in 64% and the most common facial features were a narrow and elongated face and large or prominent ears in 92% of patients. Screening of FMR1 full mutation provides the possibility for patients' further medical supports and the clinical features of FXS children obtained in this study will increase the understanding and diagnosis of FXS.

Dante Alighieri (1265-1321): an "infernal" endocrinological observation.

The year 2021 marks the 700th anniversary of Dante's death. Is it appropriate to celebrate this anniversary in a journal of endocrinology? The answer is yes-the motivation for this being found in the giants that Dante, in his Divine Comedy, places around the well that divides Circle 8 from Circle 9 of Hell. The "Supreme Poet" describes one of the giants (Nimrod, a Biblical character) as having a large and elongated face with a body of gargantuan proportions. Such a description immediately calls to mind the characteristics of acromegalic prognathism, the huge stature being the most pathognomonic aspect. Is it possible that the sharp eye of Dante had observed such a feature in people affected by actual gigantism?

Assessment of the dependence of the shape of the central incisors of the upper jaw on the type of structure of the body and skull

Is it true or myth that tall people with an asthenic type of complexion have an elongated face, long and narrow teeth, and low ones have a hypersthenic type of complexion, short and wide teeth. The article assesses the dependence of the forms of the central incisors of the upper jaw on the shape of the head, type of growth of the jaws and types of complexion of a person. Materials and methods. To assess the shape of the central incisors of the upper jaw, a group of 36 people was selected: 9 men and 27 women aged 15 to 45 years. On the basis of the obtained calculations, parameters were identified that assess the type of jaw growth: SGo: NMe, ML-NSL, ∠Biork (NSAr + SArGo + ArGoMe), NL-ML, ∠NGoMe, NBa/PtGn. Conclusions. The most common form of the maxillary central incisors is triangular and square. The rarest shape of the central incisors is round and oval. Counterclockwise rotation of the mandible is associated with the most common tooth shapes. Most often, the triangular shape of the central incisors of the upper jaw is combined with a neutral type of growth, and the square shape — with a horizontal one. An unambiguous relationship between the shape of the central incisors of the upper jaw and the shape of the head was not revealed. Patients with a square shape of the central incisors of the upper jaw more often corresponded to the asthenic type of build. 6. Patients with oval, rectangular and triangular shapes of the central incisors of the upper jaw more often corresponded to the normosthenic type of constitution. For patients with the vertical type of growth of the jaw bones, the hypersthenic type of constitution was more common.

1709 A Rare Case of Muscular Dystrophy in an Adult Diagnosed by Suspicion on High Resolution Esophageal Manometry

INTRODUCTION: Oropharyngeal dysphagia with severe upper esophageal sphincter (UES) dysfunction may be seen due to neuromuscular, neurodegenerative and structural diseases. However, the diagnosis of Myotonic Dystrophy based on interpretation of High Resolution Esophageal Manometry (HRM) is rare. CASE DESCRIPTION/METHODS: A 28-year-old Caucasian man presented with a history of dysphagia since childhood with choking and gasping during sleep. During meals he regurgitated frequently and drank large amounts of water to swallow food. He had dysphagia to both solids and liquids. Patient also noted coughs after most meals. He noted a weight loss of 25 pounds with a normal appetite. Patient wanted to eat but was worried about choking. No prior history of food allergies, asthma or food intolerances. No seasonal allergies. Past medical history notable for a normal upper endoscopy. On physical examination the patient was noted to have an elongated face with drooping of his eyelids bilaterally. He had thinning of his temporal area, jaw and anterior neck musculature and thenar wasting bilaterally. Weakness of both extremities was noted with normal reflexes. Review of prior testing was done. A Modified Barium Swallow study showed no evidence of aspiration or penetration and decreased hyolaryngeal excursion with impaired epiglottic inversion with decreased duration of the cricopharyngeal. Given the conflicting findings above, a HRM was performed in our motility lab. (See Figures 1 and 2). Solid swallows were unable to be performed due to the severe extent of the patient’s dysphagia and risk of aspiration. Based on our manometry results, we performed the following testing to rule out neuromuscular diseases prior to his referral to a neurologist. Several serologic testing was performed. (see Table 1) Based on testing, he had an elevated Aldolase and CPK with suspicion of a muscular disorder. For his absent contractility based on his HRM, he was started on Bethanechol, a cholinesterase inhibitor and muscarinic agonist at a dose of 25 mg prior to meals. Patient’s nutrition was supported with protein supplementation and a Gastrostomy-Jejunostomy tube was suggested due to significant oropharyngeal dysphagia. He was referred to the Myotonic Dystrophy Clinic. DISCUSSION: Patient’s presenting with oropharyngeal dysphagia who are found to have a hypotensive UES on HRM should spark concern for a myopathy or neurological etiology.

Reconstructing Denisovan Anatomy Using DNA Methylation Maps.

Denisovans are an extinct group of humans whose morphology remains unknown. Here, we present a method for reconstructing skeletal morphology using DNA methylation patterns. Our method is based on linking unidirectional methylation changes to loss-of-function phenotypes. We tested performance by reconstructing Neanderthal and chimpanzee skeletal morphologies and obtained >85% precision in identifying divergent traits. We then applied this method to the Denisovan and offer a putative morphological profile. We suggest that Denisovans likely shared with Neanderthals traits such as an elongated face and a wide pelvis. We also identify Denisovan-derived changes, such as an increased dental arch and lateral cranial expansion. Our predictions match the only morphologically informative Denisovan bone to date, as well as the Xuchang skull, which was suggested by some to be a Denisovan. We conclude that DNA methylation can be used to reconstruct anatomical features, including some that do not survive in the fossil record.

Cutis Tricolor

AbstractCutis tricolor is a skin abnormality consisting in a combination of congenital hyper- and hypopigmented skin lesions (in the form of paired macules, patches, or streaks) in close proximity to each other in a background of normal skin. It is currently regarded as a twin-spotting (mosaic) phenomenon. This phenomenon has been reported so far as a purely cutaneous trait, as a part of a complex malformation phenotype (Ruggieri–Happle syndrome), which includes distinct facial features, cataract, skull and vertebral defects, long bones dysplasia, corpus callosum, cerebellar and white matter anomalies, cavum vergae and holoprosencephaly, and other systemic abnormalities. Cutis tricolor has been also reported as a distinct type with multiple, disseminated smaller skin macules (cutis tricolor parvimaculata) or in association with other skin disturbances (e.g., phacomatosis achromico-melano-marmorata) or in the context of other neurocutaneous phenotypes (e.g., ataxia-telangiectasia and phacomatosis pigmentovascularis) or as a sign of complex malformation phenotypes (e.g., microcephaly and dwarfism). More than 20 studies reporting 40 cases are present in the literature with pure cutaneous or syndromic cutis tricolor phenomena and are analyzed in the present study, confirming and expanding the overall phenotype of cutis tricolor. In particular, (1) the skin abnormalities of the cutis tricolor do not evolve over time; (2) there is a typical facial phenotype with long, elongated face, thick and brushy eyebrows, hypertelorism, deep nasal bridge with large bulbous nose, and anteverted nostrils; (3) the skeletal defects are mild-to-moderate and do not progress or cause relevant orthopedic complications; (4) the neurological/behavioral phenotype does not progress and the paroxysmal events (if present) tend to decrease over time; (5) only three patients developed early onset (treatable) cataracts. Different pathologic hypotheses have been postulated, including, early or late postzygotic mutations involving the same gene loci (in the context of the so-called dydymotic theory): such mechanisms can explain the overall skin, bone, lens, and nervous system phenomena of migration of different streaks of clones in the different tissues.

Secular trend of head and face shape in adult population of Vojvodina (Serbia)

Background: Different populations show variation in the pattern of change in craniofacial dimensions over time. Earlier studies of craniofacial traits in the Republic of Serbia were carried out, without any particular reference to secular changes.Aim: The aim of the study is to determine possible changes in craniofacial dimensions among the adult population of Vojvodina (Serbia) during a 33 year period.Subjects and methods: The findings of the study are based on the comparison of data from two cross-sectional surveys. The earlier research was conducted in 1975 (n = 2600) and the second from 2001–2006 (n = 4504). Four craniofacial dimensions and body height were analysed.Results: In terms of the head dimensions, head length in males has increased substantially, while head breadth has decreased in both sexes. The total change in the cephalic index is 0.58 (males) and 0.48 (females) units per decade. Morphological face height has substantially increased, while face breadth has decreased in both sexes over this period. The total change in the facial index per decade is 0.75 units in males and 0.98 in females.Conclusion: The results point to a trend of head and face shape remodelling toward a narrower head and more elongated face, consistent with ongoing dolichocephalisation.

Duplication of 19p13.3 in 11-Year-Old Male Patient with Dysmorphic Features and Intellectual Disability: A Review.

We present a clinical report of an 11-year-old male patient with an interstitial duplication of 19p13.3 (829 kb in size) at genomic coordinates 3,804,495-4,033,722 bp (hg19) identified by chromosomal microarray analysis and review the literature from nine published reports adding knowledge regarding this chromosomal anomaly and clinical outcomes. The size of the duplication ranged from 0.83 to 8.9 Mb in the nine individuals. The young boy in our report was dysmorphic with microcephaly, abnormal craniofacial features, intellectual disability, aggression, and a heart murmur. All patients were found to have a psychomotor developmental delay and/or intellectual disability with the majority having microcephaly, intrauterine growth retardation, and hypotonia. Common craniofacial findings included a tall, prominent forehead, an elongated face, epicanthal folds, hypertelorism, prominent low-set ears, philtrum anomaly, and a small mouth. Other less common features included abnormal digits, sparse hair, and cardiac defects. Clinical features, chromosome duplication sizes, locations, and the number of genes will be summarized in a tabular form.

Cutis tricolor: a literature review and report of five new cases.

Cutis tricolor is a skin abnormality consisting in a combination of congenital hyper- and hypopigmented skin lesions (in the form of paired macules, patches or streaks) in close proximity to each other in a background of normal skin. It is currently regarded as a twin-spotting (mosaic) phenomenon and today is clear that not all cases of cutis tricolor represent one single entity. This phenomenon has been reported so far either: (I) as an purely cutaneous trait; (II) as a part of a complex malformation phenotype (Ruggieri-Happle syndrome, RHS) including distinct facial features, eye (cataract), skeletal (skull and vertebral defects, and long bones dysplasia), nervous system (corpus callosum, cerebellar and white matter anomalies, cavum vergae and holoprosencephaly) and systemic abnormalities; (III) as a distinct type with multiple, disseminated smaller skin macules (cutis tricolor parvimaculata); and (IV) in association with other skin disturbances [e.g., cutis marmorata telangectasica congenita (phacomatosis achromico-melano-marmorata)] or in the context of other skin (e.g., ataxia-telangiectasia and phacomatosis pigmentovascularis, PPV) or complex malformation phenotypes (e.g., microcephaly and dwarfism). (I) Review of the existing literature; and (II) information on our personal experience (clinical, laboratory and imaging data) on new cases with cutis tricolor seen and followed-up at our institutions during years 2010-2016. The existing literature revealed 19 previous studies (35 cases) with pure cutaneous or syndromic cutis tricolor phenomena. Our personal experience included 5 unpublished patients (3 boys; 2 girls; currently aged 2 to 14 years) seen and followed-up at our Institutions in Italy who had: (I) skin manifestations of the cutis tricolor type (N=5); (II) skeletal abnormalities including small skull (n=2), obtuse angle of mandible (n=3), mild to moderate scoliosis (n=3), vertebral defects (n=3), and long bones bowing (n=3); mild psychomotor delay (n=3); epilepsy (n=2); anomalies of the corpus callosum (n=3); and cavum vergae (n =2). This study further confirms and expands the overall phenotype of cutis tricolor. By literature review and personal experience we conclude that the skin abnormalities of the cutis tricolor type are stable over time; the skeletal defects are mild to moderate and do not progress or cause relevant orthopaedic complications; the neurological/behavioural phenotype does not progress and the paroxysmal events (when present) tend to decrease over time; there is a typical facial phenotype in some patients (long, elongated face, thick and brushy eyebrows, hypertelorism, deep nasal bridge with large bulbous nose and anteverted nostrils), which characterizes a somewhat distinct syndromic phenotype; some patients may develop early onset cataracts. The allelic dydymotic hypothesis of post-zygotic mutations likely involving the same gene loci could well explain the overall skin, bone, lens and nervous system phenomena of migration of different streaks of clones in the different tissues.

Report of a Turkish girl with Andersen-Tawil syndrome

The case is a 9-year-old girl with a history of syncope attacks for 6 years and recurrent paraplegia attacks for 1.5 years. She was diagnosed with epilepsy and was given valproate for the attacks, but no improvement was noted. Because of her paraplegia attacks, lasting between a few hours and 3 days, abnormal findings she was diagnosed with conversion. Her prenatal, natal and postnatal history was unremarkable, and her school performance was high. There was a close consanguinity between the parents. She had four healthy sibs. Her mother, maternal uncle and maternal grandmother had intermittent fatigue, numbness on the extremities. On physical examination, she had mild elongated face and dysmorphic changes on the hands. Muscle strength was normal on the upper extremities, but no muscle activity was noted on the lower extremities. She also had no response to touch and pain stimuli on the lower extremities. On laboratory investigation, serum electrolytes including potassium level, renal and liver function tests were normal. Glomerul filtration rate was 59 mL/min/m 2 . QTc interval was mild prolonged (0.45 seconds). Electromyographic examination was unremarkable. On DNA mutation analysis, no mutation of KCJN2 gene coding for Kir 2.1 protein was diagnosed. Her mother had normal serum electrolytes, but had prolonged QTc interval (0.46 seconds). Her father was completely normal for serum electrolytes and electrocardiographic examination. Unfortunately, maternal uncle and grandmother could not be examined. Based on the clinical and laboratory abnormalities she was diagnosed with Andersen-Tawil syndrome and given potassium supplementation. Her paraplegia and syncope attacks were markedly decreased after initiating potassium therapy. Now, she is in the 3rd year of follow-up. She is continued to use potassium and her paraplegia and syncope attacks noted only one attack a 2-3 months.

That’s Pretty Hard to Swallow: A Rare Case of Dysphagia Due to Myasthenia Gravis

Introduction: An 89-year-old woman with GERD and hypothyroidism presented with a 7-month history of dysphagia and odynophagia to both solids and liquids. She was admitted 1 month prior to this admission for similar symptoms and underwent an EGD, which revealed a hiatal hernia. Despite compliance with omeprazole 40 mg daily, she returned to the emergency room with worsening symptoms. She denied abdominal pain, nausea, vomiting, diarrhea, constipation, dark stools, blood per rectum, or jaundice. Physical exam revealed an elongated face with bitemporal wasting, bilateral partial ptosis, and dysarthria. Motor strength was 4/5 in both upper and lower extremities. The abdominal exam was benign. Evaluation for gastrointestinal causes of dysphagia included a video esophagram showing decreased peristalsis and a repeat EGD revealing no resistance to a balloon dilator nor evidence of stricture, rings, or masses. Due to negative GI imaging, evaluation for neurological causes of dysphagia was completed. This included MRI brain and MRA of the head & neck which were negative for infarction or stenosis of vessels. CT scan of the neck was negative for right recurrent laryngeal nerve paralysis. By hospital admission day 4, she was intubated for inability to swallow her secretions and given an NG tube for feeds. Labs revealed elevated aldolase level of 7.9. Due to suspicion for neuromuscular causes of dysphagia, electromyography was completed, revealing a neuromuscular junction abnormality. Voltage-gated Ca-channel antigen and anti-MuSK antibody were negative while acetylcholine receptor-binding antibody level was 5.63 (high), acetylcholine receptor-modulating antibody level was 30 (high), and acetylcholine receptor-blocking antibody was 83 (high), thus confirming the diagnosis of myasthenia gravis as the cause of dysphagia. Repetitive nerve stimulation showed a decremental response further solidifying the diagnosis. CT scan of the chest did not reveal presence of a thymoma. She was started on IV immunoglobulins for 5 days, prednisone 50 mg daily, and pyridostigmine 60 mg three times a day with improvement in her muscle weakness, ptosis, and dysphagia. Dysphagia as the primary presenting symptom of myasthenia gravis is very rare and has only been reported in 6-15% of cases of myasthenia gravis. Myasthenia gravis is more commonly reported as a paraneoplastic phenomenon associated with a thymoma/thymic tumor, which was absent in our case. Late-onset myasthenia gravis is more common in men and is often acetylcholine-receptor antibody negative. The age of onset along with the gender and antibody profile of our patient makes this case very unique. Our case truly increases awareness of nongastrointestinal causes of dysphagia. Disclosure - 1. Dr. Kumkum Patel--no financial relationships. 2. Dr. Jacqueline Forman--no financial relationships. 3. Dr. Bhawna Halwan--no financial relationships. 3. Dr. James Grendell-Consultant: NPS Pharmaceuticals Advisory Board.

Ecogeographical and phylogenetic effects on craniofacial variation in macaques

The widespread and complex ecogeographical diversity of macaques may have caused adaptive morphological convergence among four phylogenetic subgroups, making their phylogenetic relationships unclear. We used geometric morphometrics and multivariate analyses to test the null hypothesis that craniofacial morphology does not vary with ecogeographical and phylogenetic factors. As predicted by Bergmann's rule, size was larger for the fascicularis and sinica groups in colder environments. No clear size cline was observed in the silenus and sylvanus groups. An allometric pattern was observed across macaques, indicating that as size increases, rounded faces become more elongated. However, the elevation was differentiated within each of the former two groups and between the silenus and sylvanus groups, and the slope decreased in each of the two northern species of the fascicularis group. All allometric changes resulted in the similar situation of the face being more rounded in animals inhabiting colder zones and/or in animals having a larger body size than that predicted from the overarching allometric pattern. For non-allometric components, variations in prognathism were significantly correlated with dietary differences; variations in localized shape components in zygomatics and muzzles were significantly correlated with phylogenetic differences among the subgroups. The common allometric pattern was probably influenced directly or indirectly by climate-related factors, which are pressures favoring a more rounded face in colder environments and/or a more elongated face in warmer environments. Allometric dissociation could have occurred several times in Macaca even within a subgroup because of their wide latitudinal distributions, critically impairing the taxonomic utility of craniofacial elongation.

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion.

BackgroundTo alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD).ObjectiveTo describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS.MethodsThe study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed.ResultsCHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients.ConclusionSuspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.

Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans

New broad and potent neutralizing HIV-1 antibodies have recently been described that are largely dependent on the gp120 N332 glycan for Env recognition. Members of the PGT121 family of antibodies, isolated from an African donor, neutralize ∼70% of circulating isolates with a median IC50 less than 0.05 µg ml−1. Here, we show that three family members, PGT121, PGT122 and PGT123, have very similar crystal structures. A long 24-residue HCDR3 divides the antibody binding site into two functional surfaces, consisting of an open face, formed by the heavy chain CDRs, and an elongated face, formed by LCDR1, LCDR3 and the tip of the HCDR3. Alanine scanning mutagenesis of the antibody paratope reveals a crucial role in neutralization for residues on the elongated face, whereas the open face, which accommodates a complex biantennary glycan in the PGT121 structure, appears to play a more secondary role. Negative-stain EM reconstructions of an engineered recombinant Env gp140 trimer (SOSIP.664) reveal that PGT122 interacts with the gp120 outer domain at a more vertical angle with respect to the top surface of the spike than the previously characterized antibody PGT128, which is also dependent on the N332 glycan. We then used ITC and FACS to demonstrate that the PGT121 antibodies inhibit CD4 binding to gp120 despite the epitope being distal from the CD4 binding site. Together, these structural, functional and biophysical results suggest that the PGT121 antibodies may interfere with Env receptor engagement by an allosteric mechanism in which key structural elements, such as the V3 base, the N332 oligomannose glycan and surrounding glycans, including a putative V1/V2 complex biantennary glycan, are conformationally constrained.

Increased Vertical Dimension of Occlusion: Signs, Symptoms, Diagnosis, Treatment and Options

During the planning of oral rehabilitation, the vertical dimension of occlusion (VDO) is one of the first parameters to be measured since its improper restoration can lead to the failure of any prosthetic rehabilitation. A decreased VDO can lead to the appearance of lesions, such as angular cheilitis, facial disharmony, and temporomandibular disorders; meanwhile, an increased VDO may lead to the onset of joint and muscle pain, tension in functional speech, difficulty in swallowing, impaired chewing, tooth sensitivity due to traumatogenic forces, pathologic bone resorption, abnormal wearing of teeth, the appearance of an elongated face, and a facial expression of fatigue. Most scientific articles deal with methods and techniques for re-establishing VDO in edentulous patients or those who have lost their tooth reference due to prosthetic preparations. However, patients with increased VDO are also found in everyday practice. One treatment option for these patients is occlusal adjustment by selective tooth wear; it is still possible to perform orthodontic intrusion and/or orthognathic surgery in severe cases. The aim of this study was to discuss signs, symptoms, diagnosis, and treatment, and to report a clinical case of a patient with increased VDO.

Craniofacial characteristics of fragile X syndrome in mouse and man

For a disorder as common as fragile X syndrome, the most common hereditary form of cognitive impairment, the facial features are relatively ill defined. An elongated face and prominent ears are the most commonly accepted dysmorphic hallmarks. We analysed 3D facial photographs of 51 males and 15 females with full FMR1 mutations and 9 females with a premutation using dense-surface modelling techniques and a new technique that forms a directed graph with normalized face shapes as nodes and edges linking those with closest dysmorphism. In addition to reconfirming known features, we confirmed the occurrence of some at an earlier age than previously recorded. We also identified as yet unrecorded facial characteristics such as reduced facial depth, hypoplasticity of the nasal bone-cartilage interface and narrow mid-facial width exaggerating ear prominence. As no consistent craniofacial abnormalities had been reported in animal models, we analysed micro-CT images of the fragile X mouse model. Results indicated altered dimensions in the mandible and both outer and inner skull, with the latter potentially reflecting differences in neuroanatomy. We extrapolated the mouse results to face shape differences of the human fragile X face.

Contouring of Long Face Deformity by Structure Lipofilling

Long face may be a part of craniofacial syndrome, which can be corrected by reduction osteotomies. However, nonsyndromic long face appearance or elongated face is a common compliant that usually results from loss of the facial fat foundation due to weight loss in some individuals or familial traits in others. In this study, lipofilling or structure fat grafting of the different aesthetic zones of the face was used to contour and create well-balanced facial dimensions. The study included 84 female patients with nonsyndromic long face deformity. Structure lipofilling was performed according to the standard technique of Coleman. The width of the face was measured at 3 transverse dimensions: transzygomatic, transtemporal, and transbuccal. With an average follow-up period of 1 year, there was an increase in the transverse facial dimensions, with increased width/height facial index. More than 91% of the patients were satisfied with the results. The study concluded that long face deformity due to volume deficiency after weight loss can be corrected by lipofilling, which restores the contour with balanced facial dimensions.

Fragile X Syndrome

Recent data from a national survey highlighted a significant difference in obesity rates in young fragile X males (31%) compared to age matched controls (18%). Fragile X syndrome (FXS) is the most common cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (>200) on the promotor region of the fragile X mental retardation 1 gene (FMR1). As a result, the promotor region often becomes methylated which leads to a deficiency or absence of the FMR1 protein (FMRP). Common characteristics of FXS include mild to severe cognitive impairments in males but less severe cognitive impairment in females. Physical features of FXS include an elongated face, prominent ears, and post-pubertal macroorchidism. Severe obesity in full mutation males is often associated with the Prader-Willi phenotype (PWP) which includes hyperphagia, lack of satiation after meals, and hypogonadism or delayed puberty; however, there is no deletion at 15q11-q13 nor uniparental maternal disomy. Herein, we discuss the molecular mechanisms leading to FXS and the Prader-Willi phenotype with an emphasis on mouse FMR1 knockout studies that have shown the reversal of weight increase through mGluR antagonists. Finally, we review the current medications used in treatment of FXS including the atypical antipsychotics that can lead to weight gain and the research regarding the use of targeted treatments in FXS that will hopefully have a significantly beneficial effect on cognition and behavior without weight gain.

The phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than autosomal recessive cutis laxa type 2

Geroderma osteodysplasticum is a rare autosomal recessive disorder characterized by wrinkled skin on the dorsum of the hands and feet, osteopenia, prognathism, and an elongated and lax face. The mutated gene was identified as GORAB (SCYL1BP1). As well, the PYCR1 gene also was shown to be mutated in a similar disease, designated cutis laxa, autosomal recessive, type IIB (ARCL2B) or cutis laxa with progeroid features. We describe here the clinical findings in four affected individuals in a family with geroderma osteodysplasticum with mental retardation and a homozygous mutation in PYCR1. Although the disease resulting from recessive mutations in that gene has been recently designated ARCL2B, some clinical features, such as prognathism, elongated and lax face, osteopenia and limitation of skin wrinkling to the dorsum of hands and feet, in the patients reported here as well as in others reported with PYCR1 mutations, are generally more common in geroderma osteodysplasticum resulting from recessive GORAB mutations. While the patients with GORAB mutations have severe osteopenia, the patients with PYCR1 mutations have severe mental retardation. In conclusion, the phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than ARCL2B.