Hypertelorism Research Articles

Morphological examination of a preterm neonate with atypical Pallister-Killian syndrome

Pallister-Killian syndrome (PKS) is a rare genetic disorder which is cytogenetically characterized by a tissue limited mosaic distribution of isochromosome 12p (tetrasomy 12p). This chromosomal anomaly may be detected in fibroblasts and in bone marrow cells, in amniocytes, chorionic villus and other foetal tissues, whereas it is absent in peripheral lymphocytes. The percentage of abnormal cells in fibroblasts decreases with the ageing, so adult patients may be undiagnosed.We report on a preterm male neonate of 1320 gr of weight, born at a gestational age of 29-30 weeks. He had severe respiratory distress and died after a few hours, in spite of intensive resuscitation. The external examination showed a disproportionate large face and low-set ears, limbs of normal length, with normal hands and feet, normal genitalia. At the autopsic examination all the thoracic, abdominal and pelvic organs were normal, the palate showed a schisis in the posterior side of the arch; the external appearance of the brain was normal, with hyperaemic pial membrane. The cytogenetic analysis on skin fibroblasts showed the presence of a supernumerary metacentric chromosome, consistent with an isochromosome 12p. Subsequent interphasic FISH with a centromeric probe detected tetrasomy 12p in mosaic.The postnatal phenotype of PKS is quite severe and include coarse facies with a high forehead, sparce scalp hair, hypertelorism, broad nasal bridge, hypotonia, streaks of hypo-hyperpigmentation. Hydramnios, congenital diaphragmatic hernia and micromelia, of predominantly rhizomelic type are frequent echographic signs during the pregnancy. Hydrops fetalis, hygroma colli, increased nuchal translucency (INT), foetal overgrowth and ventriculomegaly are less frequently reported. In the present case no foetal malformations were evident during the pregnancy, and the facial dysmorphisms and congenital malformations described in PKS were absent at the morphological and autopsic examination of the newborn. This suggests that PKS could be suspected, and then verified on skin fibroblasts, even in absence of significant congenital malformations, mainly in dysmorphic patients cytogenetically normal at standard cytogenetics on peripheral lymphocytes.

Doença celíaca associada à tireoidite de Hashimoto e síndrome de Noonan

OBJETIVO: Relatar o caso clínico de uma criança portadora de doença celíaca, tireoidite de Hashimoto e síndrome de Noonan. DESCRIÇÃO DE CASO: Menina de dez anos e seis meses, branca, apresentando história de diarreia líquida há cinco meses e "aumento da barriga". Ao exame, mostrava peso de 20.580g (p<3), estatura de 114cm (p<3), hidratada, descorada 2+/4+ e consciente. Presença de fácies triangular, com hipertelorismo ocular aparente, posição antimongoloide das fendas palpebrais, orelhas em abano de baixa implantação, micrognatia, pescoço curto e pectus excavatum. O abdome mostrava-se globoso, flácido, indolor, com hérnia umbilical, fígado a 2cm do rebordo costal direito, linfedema em membro superior direito e edema de membros inferiores. Nos exames subsidiários, havia anemia microcítica e hipocrômica, déficit de proteínas totais, tireoidite de Hashimoto e atraso de cinco anos na idade óssea. Na ultrassonografia abdominal, as alças intestinais estavam levemente dilatadas. Devido ao linfedema e à diarreia crônica, a hipótese inicial foi de linfangiectasia intestinal, confirmada pela biópsia jejunal, que ainda mostrou padrão compatível de doença celíaca. O cariótipo foi 46XX com diagnóstico clínico de síndrome de Noonan. COMENTÁRIOS: As doenças autoimunes se associam; no caso apresentado, a doença celíaca se associou à tireoidite de Hashimoto, possivelmente pela presença de antígenos do sistema HLA. Já a associação de doença celíaca à síndrome de Noonan é muito rara, sendo este o terceiro relato na literatura.

UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients

We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present in patients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck.

Noonan Syndrome : A Case Report

Noonan syndrome (NS) is a developmental disorder characterized by dysmorphic facial features in association with short stature, mental retardation and congenital heart disease. NS may be sporadic or inherited as an autosomal dominant or recessive trait. The children with NS usually have ocular hypertelorism, downslanting palpebral fissures, low-set ears and a webbed neck, chest deformity. In addition, oral features include micrognathia, high arched palate, dental malocclusion, dental anomalies and rarely, cleft palate. The phenotype of NS bears similarities to that of Turner syndrome. However, NS occurs in both males and females with a normal sex chromosome 46, XX and 46, XY constitution. This case presents the intermittent treatment of an 8-year-old girl who was referred from a local clinic for the extraction of supernumerary teeth and treatment of dental caries. The focus of this case report is the oral aspects on NS and particularities of the dental treatment in subjects affected by this genetic disease.

Ocular Manifestations of Apert and Crouzon Syndromes

There are significant differences in the ocular manifestations of Apert and Crouzon syndromes. Here, we present qualitative and quantitative data about the oculo-orbital region to demonstrate these differences. Although ocular protosis and hypertelorism characterize both disorders, the nature of the orbital dystopia differs. In Crouzon syndrome, ocular proptosis is primarily caused by retrusion of the lateral and inferior orbital margins with a very short orbital floor. In Apert syndrome, the eyeglobe actually protrudes in relation to the cranial base and to the orbit, probably resulting from marked protrusion of the lateral orbital wall. The implications account for some of the differences encountered. Asymmetry is associated with Apert syndrome frequently. Exotropia is found in Crouzon syndrome, whereas the V pattern is more characteristic in Apert syndrome with divergent upgaze and esotropic downgaze. Subluxation of the eyeglobe is found in some cases of Crouzon syndrome but is not found in Apert syndrome. Optic atrophy found in approximately 20% of Crouzon syndrome patients is not characteristic of Apert syndrome. Structural alterations of the extraocular muscles have been associated with some cases of Apert syndrome, suggesting that ocular motility disturbances in Apert syndrome may not be caused solely by mechanical factors. Absence of the superior rectus and other extraocular muscles has been recorded. Furthermore, albinoid alterations of the fundus have also been associated with Apert syndrome.

Importance of Muscle Movement for Normal Craniofacial Development

After the craniofacial structures have completed embryologic development, movement of facial muscles begins. Paraxial mesoderm of the first (mastication) and second pharyngeal (facial expression) arches gives rise to the muscles of the craniofacial area. Muscles derived from the third and fourth pharyngeal arches are involved in swallowing and vocalization. For the human newborn face to have a normal morphologic appearance, contractions of these muscles must occur to stimulate forward growth of bone, cartilage growth, and facial muscle bulk. Facial muscles begin to contract between 6 and 8 weeks of embryonic development and can be observed on prenatal ultrasound by 9 weeks after fertilization. Lack of craniofacial muscle contractions may lead to ocular hypertelorism, flat zygoma and midface, high bridge of the nose, depressed tip of the nose, small and open mouth, trismus, microretrognathia, small tongue, and abnormal palate (high arch, bifid uvula, submucous cleft, and cleft palate).

Malformations of Cortical Development in Patients with Midline Facial Defects and Ocular Hypertelorism

We studied the neuroimaging and neurophysiological aspects of 17 patients with midline facial defects with ocular hypertelorism (MFDH). The investigation protocol included a previous semistructured questionnaire about family history; gestational, neonatal, and postnatal development; and dysmorphologic and neurologic evaluation. Recognized monogenic disorders and individuals with other well-known conditions were excluded. All patients had high resolution magnetic resonance imaging (MRI) with multiplanar reconstruction (MPR) and routine electroencephalograms (EEGs). We detected abnormalities in five patients whose MRIs had been previously reported as normal. MRI showed central nervous system (CNS) structural abnormalities in all patients, which included commissural alterations in 16/17 (94%), malformations of cortical development in 10/17 (58%), disturbances of neural tube closure in 7/17 (42%), and posterior fossa anomalies in 6/17 (35%). Some patients had more than one type of malformation occurring at different stages of the embryonary process. EEGs showed epileptiform activity in 4/17 (24%) and background abnormalities in 5/17 (29%) of patients. This study clearly demonstrated the presence of structural and functional neurologic alterations related to MFDH. Therefore, the CNS anomalies cannot be considered incidental findings but an intrinsic part of this condition, which could be related to environmental effects and/or genetic mutations. These findings would provide a basis for future investigations on MFDH and should also be considered when planning rehabilitation.

Investigation of the 22q11.2 candidate region in patients with midline facial defects with hypertelorism

Midline facial defects with hypertelorism (MFDH) are mainly characterized by ocular hypertelorism and bifid nose. They are often associated with structural and functional anomalies of the central nervous system similar to those found in 22q11.2 deletion syndromes. In addition, there are some isolated reports of MFDH and 22q11.2 deletion. These findings suggest that MFDH may be part of the spectrum of 22q11.2 deletion syndromes. To test this hypothesis, 10 individuals with MFDH were analyzed by fluorescent in situ hybridization (FISH), but no 22q11.2 deletion was detected. In view of this result, the TBX1 gene located within the 22q11.2 candidate region was screened. A new sequence variant (1132GA) was identified in one patient. This variant was not found in 110 control individuals genotyped. Considering the rarity of this condition and results of this study, the involvement of the 22q11.2 chromosomal region in the pathogenesis of MFDH could not be excluded.

Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome

Generation of reprogrammed induced pluripotent stem cells (iPSC) from patients with defined genetic disorders promises important avenues to understand the etiologies of complex diseases, and the development of novel therapeutic interventions. We have generated iPSC from patients with LEOPARD syndrome (LS; acronym of its main features: Lentigines, Electrocardiographic abnormalities, Ocular hypertelorism, Pulmonary valve stenosis, Abnormal genitalia, Retardation of growth and Deafness), an autosomal dominant developmental disorder belonging to a relatively prevalent class of inherited RAS-MAPK signaling diseases, which also includes Noonan syndrome (NS), with pleiomorphic effects on several tissues and organ systems1,2. The patient-derived cells have a mutation in the PTPN11 gene, which encodes the SHP2 phosphatase. The iPSC have been extensively characterized and produce multiple differentiated cell lineages. A major disease phenotype in patients with LEOPARD syndrome is hypertrophic cardiomyopathy. We show that in vitro-derived cardiomyocytes from LS-iPSC are larger, have a higher degree of sarcomeric organization and preferential localization of NFATc4 in the nucleus when compared to cardiomyocytes derived from human embryonic stem cells (HESC) or wild type (wt) iPSC derived from a healthy brother of one of the LS patients. These features correlate with a potential hypertrophic state. We also provide molecular insights into signaling pathways that may promote the disease phenotype.

Novel deletion at Xq24 including the UBE2A gene in a patient with X-linked mental retardation

By using an in-house bacterial artificial chromosome-based X-tilling array, we detected a 0.4 Mb novel deletion at Xq24 that included UBE2A in a 4-year-old and 10-month-old boy with mental retardation and various other characteristics inherited from his mother; for example, marked developmental delay, synophrys, ocular hypertelorism, esotropia, low nasal bridge, marked generalized hirsutism and seizure. Although additional nine transcripts around UBE2A were also defective, a phenotypic similarity with a recently reported X-linked familial case involving a novel X-linked mental retardation syndrome and a nonsense mutation of UBE2A indicates a functional defect of UBE2A to be responsible for most of the abnormalities in these cases. Because some characteristics, such as congenital heart disease and proximal placement of the thumb, were not described in the family reported previously, suggesting genes other than UBE2A within the deleted region to be responsible for those abnormalities.

Acute Motor and Sensory Axonal Neuropathy in LEOPARD Syndrome

A case of acute predominantly axonal motor and sensory neuropathy (AMSAN) is reported in a 16-year-old boy with LEOPARD syndrome (the acronym represents lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness). The presentation was atypical for acute motor and sensory axonal neuropathy, in that this patient had progression of symptoms of more than 4 weeks and there were signs of reinnervation in the acute phase. Treatment response to intravenous immunoglobulins was excellent. In patients with LEOPARD syndrome and acute neuropathies, treatment with intravenous immunoglobulins should be considered.

Molecular and clinical analysis ofRAF1in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation

Noonan syndrome (NS) and related disorders are autosomal dominant disorders characterized by heart defects, facial dysmorphism, ectodermal abnormalities, and mental retardation. The dysregulation of the RAS/MAPK pathway appears to be a common molecular pathogenesis of these disorders: mutations in PTPN11, KRAS, and SOS1 have been identified in patients with NS, those in KRAS, BRAF, MAP2K1, and MAP2K2 in patients with CFC syndrome, and those in HRAS mutations in Costello syndrome patients. Recently, mutations in RAF1 have been also identified in patients with NS and two patients with LEOPARD (multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) syndrome. In the current study, we identified eight RAF1 mutations in 18 of 119 patients with NS and related conditions without mutations in known genes. We summarized clinical manifestations in patients with RAF1 mutations as well as those in NS patients withPTPN11, SOS1, or KRAS mutations previously reported. Hypertrophic cardiomyopathy and short stature were found to be more frequently observed in patients with RAF1 mutations. Mutations in RAF1 were clustered in the conserved region 2 (CR2) domain, which carries an inhibitory phosphorylation site (serine at position 259; S259). Functional studies revealed that the RAF1 mutants located in the CR2 domain resulted in the decreased phosphorylation of S259, and that mutant RAF1 then dissociated from 14-3-3, leading to a partial ERK activation. Our results suggest that the dephosphorylation of S259 is the primary pathogenic mechanism in the activation of RAF1 mutants located in the CR2 domain as well as of downstream ERK.

A Korean Family with the Muenke Syndrome

The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. The birth prevalence is approximately one in 10,000 live births, accounting for 8-10% of patients with coronal synostosis. Although MS is a relatively common diagnosis in patients with craniosynostosis syndromes, with autosomal dominant inheritance, there has been no report of MS, in an affected Korean family with typical cephalo-facial morphology that has been confirmed by molecular studies. Here, we report a familial case of MS in a female patient with a Pro250Arg mutation in exon 7 (IgII-IGIII linker domain) of the FGFR3 gene. This patient had mild midfacial hypoplasia, hypertelorism, downslanting palpebral fissures, a beak shaped nose, plagio-brachycephaly, and mild neurodevelopmental delay. The same mutation was confirmed in the patient's mother, two of the mother's sisters and the maternal grandfather. The severity of the cephalo-facial anomalies was variable among these family members.

A new autosomal recessive syndrome characterized by ocular hypertelorism, distinctive face, mental retardation, brachydactyly, and genital abnormalities

We report on three individuals of Muslim Arab origin from a village located in Northern Israel affected by an apparent autosomal recessive syndrome characterized by distinctive facial phenotype of which the most prominent feature is ocular hypertelorism. The other clinical features of the syndrome include variable degree of mental retardation, genital abnormalities dominated by short penis, and skeletal abnormalities including chest deformity (combination of upper pectus carinatum with lower pectus excavatum), and short palms with broad short fingers. Affected individuals displayed distinctive facial features including upslanting palpebral fissures, thick eyebrows, long philtrum, wide mouth with thin upper lip and upturned corners of the mouth, widow's peak, broad nasal bridge, and simple ears with fleshy overfolded helices. This phenotype does not fully meet typical diagnostic features of any known condition.

Pseudoaminopterin syndrome: Clinical report with new characteristics

Fetuses exposed to aminopterin during the 8th-9th week of development may show aminopterin embryophathy (AE). Surviving children have a specific phenotype that includes unusual face, skull, and skeletal abnormalities. Fraser et al. [Fraser et al. (1987); Clin Genet 32:28-34] described two children with multiple malformations characteristic of the aminopterin syndrome but without history of exposure to aminopterin in the mothers and suggested that this represents a new syndrome, the aminopterin syndrome-like sine aminopterin (ASSA) syndrome. Here we describe a 9-year-old girl, born to unaffected first cousin parents. She has short stature, microcephaly, broad forehead with high hair implantation; sparse and fine hair, areas of alopecia; arched eyebrows with upturned hair, synophris; ocular hypertelorism, epicanthal folds, palpebral ptosis; oligodontia; low-set and small ears with hypoplasia of antihelices; brachydactyly, clinodactyly of both 4th and 5th fingers; hypoplasia of the 4th metacarpal and clinodactyly of the 4th and 5th toes; overlap of the second over the third toe; bilateral hip luxation; patent foramen ovale; left posterior diaphragmatic hernia, absence of spleen and horseshoe kidney. She, her mother and her brother have a karyotype of 46,XX, with an inv(9)(p12q13) polymorphism. Although this patient has some characteristics did not described before in patients with ASSA such as, palpebral ptosis, oligodontia, left posterior diaphragmatic hernia, absence of spleen, and horseshoe kidney, her phenotype strongly suggest she has the pseudoaminopterin syndrome. However, we do not exclude the possibility that this is a different condition not described previously.

Congenital hydrocephalus in an Egyptian baby with trisomy 18: a case report

IntroductionTrisomy 18 is the second most common autosomal trisomy after Down syndrome (trisomy 21). A variety of anomalies of the central nervous system are observed in cases of trisomy 18. The association between trisomy 18 and congenital hydrocephalus is very rare.Case presentationA 4-month-old male Egyptian baby boy was referred to Assiut University hospital for evaluation of his large-sized head. The initial clinical examination revealed facial dysmorphism including a prominent wide forehead, wide anterior fontanel, bushy eyebrows, synophrosis, small palpebral fissures, ocular hypertelorism, high arched palate, depressed nasal bridge, low-set ears, micrognathia, bilateral clenched hands with over lapping fingers, rocker-bottom feet and penile hypospadius. A computed tomography scan of the patient's head showed a dilatation of all the ventricular systems of the brain that suggested hydrocephalus. A chromosome analysis of his peripheral blood confirmed a trisomy of chromosome 18 (47, XX+18). The hydrocephalus was treated with a ventriculoperitoneal shunt because of the abnormal increase in his head circumference. He was discharged home on nasogastric feeds at the age of 5 months. Despite the advice of the medical team, his parents did not bring him for further follow up. He died at the age of 7 months due to a sudden cardiorespiratory arrest at home.ConclusionMicrocephaly is not mandatory for the diagnosis of trisomy 18 syndrome because some cases of trisomy 18 can be associated with other anomalies of the central nervous system, including hydrocephalus. There is no proven explanation for this association, and the management of hydrocephalus in such a situation is not different from the usual course of management.

Malformations of cortical development in patients with midline facial defects and ocular hypertelorism

Malformations of cortical development in patients with midline facial defects and ocular hypertelorism

LEOPARD syndrome with recurrent PTPN11 mutation Y279C and different cutaneous manifestations: two case reports and a review of the literature

LEOPARD syndrome (LS) is a heterogeneous disease characterised mainly by cutaneous manifestations. LEOPARD is the acronym for its major features-multiple lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis, abnormalities of (male) genitalia, retardation of growth and sensorineural deafness. As clinical manifestations are variable, molecular testing is supportive in the diagnosis of LS. We describe two unrelated LS cases with a common PTPN11 mutation Y279C and with completely different clinical features including distinct changes in skin pigmentation. In patient 1, the first complaint was hyperactive behaviour. First lentigines were presented at birth, but intensive growth began at the age of 2-4 years. Multiple dark lentigines were located mainly on the face and the upper part of the trunk, but the oral mucosa was spared. Patient 2 was born from induced labour due to polyhydramnion, and in the second week of life, mitral valve insufficiency and hypertrophic cardiomyopathy were diagnosed. Rapid growth of lentigines began at the age of 3 years. These are mostly located in the joint areas in the lower extremities; the face and upper trunk are spared from lentigines. In both cases, the rapid growth of lentigines made it possible to shift the diagnosis towards LS. Clinicians should give more consideration to rare genetic syndromes, especially in the case of symptoms from different clinical areas.

Dystonia, autoimmune disease and cerebral white matter abnormalities in a patient with 18p deletion

Dystonia is a clinically and genetically heterogeneous disorder of movement characterized by involuntary and sustained muscle contractions and rigid postures affecting one or more sites of the body. It can be classified according to the distribution of affected body parts, age of onset and etiology 1 . Up to now, at least 15 different loci (DYT1–DYT15) have been described in this condition 1,2 . Adult-onset idiopathic torsion dystonia affecting specific parts of the body, such as the eye (blepharospasm), neck (cervical dystonia), and hand (writer’s cramp) has been associated with the DYT7 locus, located in the short arm of chromosome 18 1-3 . Autoimmune diseases have been considered conditions associated with reactions of the immune system against selfantigens or body systems. They are disorders often associated with severe and chronic morbidity. In spite of recent advances, much of their etiology is still unknown 4 . We describe a rare case of a patient with 18p deletion syndrome presenting focal dystonia, Hashimoto thyroiditis, vitiligo and cerebral white matter abnormalities. CaSe The patient is a 30 year old white woman, the fourth child of a non-consanguineous couple, without any history of similar cases in the family. The patient was born full-term, with a Cesarean section, after a pregnancy without intercurrences. During her first year of life, she had several episodes of infection (oti tis and tonsillitis) as well as constipation where laxative use was needed. At 3 months, she had a convulsive crisis during fever. In relation to her neuropsychomotor development, the mother recalls she supported her own head at 6 months and pronounced her first words at the age of three. The patient was also unable to accompany normal school, failing several grades. After a long period without intercurrences, she began with blepharospasm together with cervical dystonia. She presented telarche at the age of 12 and menarche at 13, and at around 20 she began with menstrual irregularity. The hormonal evaluation conducted later diagnosed hypothyroidism due to Hashimoto thyroiditis. During the physical exam at the age of 30, she presented obesity (weighing 70 kg, between the 90–97 percentiles), short stature (149 cm, under the 3 percentile), brachycephaly, but without microcephalia (head circumference of 53 cm – between the 2–50 percentiles), rounded face, ocular hypertelorism (interpupillary distance higher than the 97 percentile), ptosis, blepharospasm, corneal opacification, hypoplasia of the middle third of the face, broad nasal bridge, high palate, short and broad neck, low posterior hairline, broad thorax and accentuated cervical kyphosis (Figs 1A and B). She also had dextroconvex thoracic scoliosis, small hands and feet with hyperconvex nails (Figs 1C and D) and achromic spots of different sizes, spread about the body (thorax, dorsum and members), and vitiligo was diagnosed. The face remained in a fixed position, always turned to the right and downwards (Figs 1A and B). Nuclear magnetic resonance of the skull revealed a dilated ventricular system, with the presence of multiple hypersinal foci at T2 and DP in the semi-oval centers, without gadolinium impregnation, suggestive of demyeliminating lesions, and around the lateral ventricles and third ventricle, suggestive of periependimal leukomalacia (Fig 2A). Electroencephalograph assessment was normal. The thorax radiograph revealed hyperkyphosis with a reduction in body height at the seventh thoracic vertebra and dextroconvex thoracic scoliosis. Ophthalmological evaluation verified the presence of intense photophobia, bilateral keratocone with lower conjunctival pannus in the right eye and the entire left eye. Chromosomal analysis through GTG banding karyotype revealed a deletion involving the short arm of chromosome 18: 46,XX,del(18)(p11.1) (Figs 2B and 2C). The karyotype of the parents was normal.

Craniometaphyseal dysplasia: A case report

Craniometaphyseal dysplasia (CMD) is a rare genetically transmitted bone dysplasia characterized by alterations in the development of the craniofacial bones with abnormal remodeling of the metaphyses. Sclerosis of the skull bones can lead to cranial nerve compression that finally may result in hearing loss and facial palsy. CMD occurs in an autosomal dominant (AD) (MIM 123000) and an autosomal recessive (AR) form (MIM 218400). Sclerosis of cranial bones is usually much more severe in the AR form. We present a 36-year-old male with a previous diagnosis of Paget disease. The examination reveals prognathism, ocular hypertelorism, mixed bilateral hypoacusia, nasal bossing, a class III malocclusion and a narrow palatal vault. The patient necessitated several dental extractions, surgical procedures were conducted, and a biopsy of the alveolus was performed and the sample underwent histological examination. The histological report led to an exclusion of the previous diagnosis of Paget disease. The final diagnosis of autosomal dominant CMD was confirmed by the molecular testing of the CMD gene (ANKH).