Mesomelic Brachymelia Research Articles

Clinical and Genetic Characterization of Upper Extremity Anomalies in Robinow Syndrome

PURPOSE: Robinow syndrome (RS) is an extremely rare dwarfing syndrome manifesting as craniofacial, genital, and extremity anomalies.1 However, due to the low prevalence and phenotypic heterogeneity of this syndrome, a detailed description of associated upper extremity anomalies does not currently exist.2–5 This study seeks to characterize upper extremity anomalies in the context of known genetic defects to assist in timely and accurate diagnosis of RS. METHODS: Patients with clinically identified RS were invited to our institution for multidisciplinary evaluation. A total of 18 patients were evaluated by plastic surgery, urology, orthopedic surgery, neuropsychology, and genetics teams. Twelve patients ultimately agreed to genetic testing and were found to have a genetic variant of RS. Limb anomalies were surveyed and documented by 3 members of the plastic surgery team with particular attention to the upper extremity. Upper extremity findings were compared to individual genetic variants to elucidate any correlations. RESULTS: A total of 5 genetic variants were identified. Mesomelia (47%) was the most common skeletal dysplasia. Rhizomelia (33%) was limited to patient with variants of the DVL1 and NXN genes. Eight distinct hand anomalies were identified, the most being brachydactyly (92%), broad thumbs (83%), and clinodactyly (75%). Brachydactyly and broad thumbs in particular were evident across all genetic variants. The most common functional deficit was decreased forearm rotation (57%), which was seen in all genetic variants aside from an X-linked GPC4 variant. One patient with a mutation of the NXN gene demonstrated skeletal dysplasia without hand anomalies. CONCLUSION: A trained hand surgeon should be aware of the common findings associated with Robinow syndrome. This is the first study to correlate the genotypic and phenotypic presentation of patients with a confirmed diagnosis of RS. A thorough understanding of the breadth of RS-associated hand anomalies can aid in early identification and proactive management of sequelae. REFERENCES: 1. Robinow M, Silverman FN, Smith HD. A newly recognized dwarfing syndrome. Am J Dis Child. 1969;117:645–651. 2. Bain MD, Winter RM, Burn J. Robinow syndrome without mesomelic brachymelia: a report of five cases. J Med Genet. 1986;23:350–354. 3. Mazzeu JF, Pardono E, Vianna-Morgante AM, et al. Clinical characterization of autosomal dominant and recessive variants of Robinow syndrome. Am J Med Genet A. 2007;143:320–325. 4. Bunn KJ, Lai A, Al-Ani A, et al. An osteosclerotic form of Robinow syndrome. Am J Med Genet A. 2014;164A:2638–2642. 5. Patton MA, Afzal AR. Robinow syndrome. J Med Genet. 2002;39:305–310.

Orofacial findings and dental care management in a patient with Robinow Syndrome

Introduction: Robinow syndrome is a rare genetic disorder of skeletal development. It is characterized by short stature, facial dysmorphisms and orodental anomalies, underdeveloped genitalia, mesomelic brachymelia. Case Report: A 6 year old girl with Robinow Syndrome was referred in the Center for Formation of Human Resources Specialized in Dental Care to Special Needs Patients (Ribeirao Preto, Sao Paulo, Brazil) for evaluation. Medical history investigation and clinical examination were observed in short stature, facial dimorphism and hypoplastic genitalia. Orofacial findings showed retrognathism, a mid-line hemangiomaapproximately 1 cm wide with upturned borders, bifid tongue, ankyloglossia, general gingival hypertrophy, deep bite and mild tooth crowding. Cardiac abnormality and neuromotor developmental delay consisted of systemic manifestations present which demanded individualized dental care. The dental treatment consisted of preventive and restoratives procedures to adequate the oral health condition of the patient and orthodontic treatmentwas planned. The patient has been in follow-up for six years. Conclusion: Orofacial anomalies and other alterations found in the present case contributed to complement the orofacialfindings described in the literature and to assist in diagnosis of the syndrome. In this case, amultiprofessional team and integral treatment were essential to rescue oral health and improvelife quality of the patient.

Orofacial manifestations of Robinow’s Syndrome: a case report in a pediatric patient

Robinow's syndrome (Online Mendelian Inheritance in Man [OMIM] 268310), or fetal facies syndrome, is a rare genetic disorder causing autosomal dominant and recessive forms. This syndrome includes a series of anomalies such as short stature, characteristic facial dysmorphism (fetal facies), genital hypoplasia, and mesomelic brachymelia. The purpose of the present case is to describe the orofacial manifestations of the syndrome in a pediatric patient: craniofacial features, triangular mouth and a long upper lip philtrum, ankyloglossia, a shortened tongue devoid of tongue tip, a geographic tongue, arched palate, gingival hyperplasia, dental abnormalities (misaligned and crowded teeth), and delayed tooth eruption.

Midline cleft of the lower lip associated with Robinow syndrome

Robinow syndrome (also named "fetal face syndrome") includes a series of anomalies including mesomelic brachymelia, bifid terminal phalanges of the hands and feet, abnormalities of vertebrae and ribs, and hypoplastic external genitalia. A midline cleft of the lower lip and mandible is an extremely rare maxillofacial deformity. Seventy cases have so far been described to our knowledge. We report a patient with Robinow syndrome and midline cleft of the lower lip and mandible and describe the reconstruction of these anomalies. We propose that this anomaly should be added to the range of malformations associated with the syndrome.

A lethal osteochondrodysplasia with mesomelic brachymelia, round pelvis, and congenital hepatic fibrosis: two siblings born to consanguineous parents

We report a hitherto unknown, lethal osteochondrodysplasia in two Japanese siblings born to consanguineous parents. The skeletal abnormalities are characterised by mesomelic brachymelia with bowed forearms, a round pelvis with shortened greater sciatic notches, an ossification defect of the pubic bones, and absence of ossification centers in the cervical vertebral bodies. The associated visceral anomalies comprised periportal fibrosis and cystic dysplasia of the intrahepatic bile ducts, pancreatic ductal ectasia, a simple renal cyst, microcephaly with multifocal laminar necrosis and ectopic gray matter, dysplastic tracheobronchial cartilage, abnormal lobulation of the lung, diaphragmatic hernia, and stenotic pulmonary valve. Thrombocytopenia was present but megakaryocytes were slightly increased in the bone marrow. The patients showed various dysmorphic features including aniridia, a long palpebral fissure, prominent nasal bridge, beaked nose, flat philtrum, low-set fleshy ears, micrognathia with submucosal cleft palate, and multiple joint contractures.

Redefining the Genital Abnormality in the Robinow Syndrome

Purpose We defined the anatomical structure of the male genital abnormality in the Robinow syndrome. Features of this syndrome include mesomelic brachymelia of the arms, bifid terminal phalanges of the hands and feet, characteristic facies, skeletal anomalies and hypoplastic external genitalia. Materials and Methods Penile anatomy of 3 patients with the Robinow syndrome was assessed using computerized tomography and magnetic resonance imaging. Results were compared to those of 4 controls who underwent imaging for pelvic malignancies. Results Cross-sectional imaging showed that normal penile crura were inserted onto the anteromedial aspect of the pubic bone. In contrast, in the Robinow syndrome they were inserted inferiorly and posteriorly onto the medial aspect of the ischial tuberosity. In addition, the crura in the Robinow syndrome extended posterior to a line intersecting both femoral shafts. Compared to controls, there was a significant gap between the symphysis pubis and dorsal aspect of the penis. Conclusions The penile anomaly in the Robinow syndrome is due to abnormal insertion of the penile crura, resulting in a penis that appears shorter and more inferiorly placed between the legs.

Velo‐facio‐skeletal syndrome in a mother and daughter

We present a woman and her daughter with an apparently new short stature syndrome associated with facial and skeletal anomalies and hypernasality. Manifestations included hypertelorism with broad and high nasal bridge, epicanthal folds, narrow and high arched palate, mild mesomelic brachymelia, short broad hands, prominent finger pads, hyperextensibility of hand joints, small feet, nasal voice, and normal intelligence. The mother had short stubby thumbs and the daughter had posteriorly angulated ears and delayed bone age. The morphology of the nose and the hypernasality are reminiscent to those in the velo-cardio-facial syndrome. High resolution banding and fluorescent in situ hybridization studies showed no evidence of 22q11 deletions. Differentiation from Aarskog syndrome and Robinow syndrome is discussed.

Sirengomyelisi Olan Bir Robinow Sendromu

Robinow syndrome is a rare autosomal dominant or recessive genetic disorder characterized by typical facial appearence fetal face mesomelic brachymelia and genital hypoplasia An 8 month old girl admitted with short stature and brachydactylia was diagnosed as Robinow syndrome on the grounds of the following findings: fetal face appearence consisting of macrocephalia hypertelorism facial hypoplasia small upturned nose triangular mouth and micrognathia mesomelic brachymelia arch anomalies in all thoracic vertebrae and ribs with fusion anomalies and genital hypoplasia Magnetic resonance imaging of the spine revealed syringomyelia Key words: nbsp;Robinow Syndrome Fetal Face Syndrome Syringomyelia Autosomal Recessive Inheritance Costo Vertebral Anomalies

Autosomal recessive Robinow‐like syndrome with anterior chamber cleavage anomalies

We describe 2 sisters with short stature, mesomelic brachymelia, macrocephaly, hypoplastic genitalia, and anterior chamber cleavage anomalies. Many of their manifestations have been described in individuals with Robinow syndrome; however, the anterior chamber cleavage anomalies seen in both girls, hydrocephalus seen in the younger sister, and apparent autosomal recessive inheritance do not characterize the Robinow syndrome. The syndrome present in these sisters most likely represents a previously undescribed autosomal recessive syndrome.

THE MOHR AND MAJEWSKI SYNDROMES: OVERLAPPING PHENOTYPES

The Mohr syndrome (oral-facial-digital syndrome, type II) and the Majewski syndrome (a form of short rib-polydactyly) are currently described as separate dysmorphic syndromes with autosonal recessive inheritance. The Mohr syndrome is characterized by median cleft of the upper lip, cleft tongue, oral hamartomas, bimanual polydactyly, hallucal reduplication and a normal lifespan. The Majewski syndrome is characterized by cleft lip, hypoplastic epiglottis, short ribs, genitourinary anomalies, mesomelic brachymelia, pre- and postaxial polydactyly and death in infancy.We studied two unrelated female infants with features common to both syndromes. One had median pseudocleft of the upper lip, lingual nodules, short ribs, urogenital sinus, hydrometrocolpos, short tibias and hallucal reduplication. She failed to thrive and died at 4 months of age. The second infant had median pseudocleft of the upper lip, lingual nodules, micrognathia, epiglottic hypoplasia, pre- and postaxial polydactyly and hallucal reduplication. Despite tracheostomy, she died at 11 months of age. On post-mortem exam a single atrium and ventricular septal defect were found. Both infants had orofacial and digital features typical of the Mohr syndrome. However, one had the skeletal and genitourinary abnormalities and the other, the hypoplastic epiglottis of the Majewski syndrome. The presence in our patients of anomalies typical of the Mohr and Majewski syndromes may indicate that these syndromes represent two extremes of the same disorder.

Mesomelic dwarfism with hemivertebrae and small genitalia (the Robinow syndrome).

Three families are presented in which four children have mesomelic brachymelia, hemivertebrae, short digits, and genital hypoplasia along with peculiar facies characterized by a flat profile, mild ocular hypertelorism, a short, broad upturned nose, and a small midline cleft in the lower lip. This condition should be suspected in any newborn male who has no visible penis or a micropenis. The children had normal birth weights and normal results for endocrine, biochemical, and chromosome studies. Available evidence suggests that the condition is heritable, but the mode of transmission is not clear. In view of the complex vertebral, extremity, and genital changes, the defective gene probably exerts its effect between the 8th and 12th weeks of gestation.