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Roberts Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Roberts syndrome (RBS) is an autosomal recessive disorder characterized by pre/postnatal growth retardation (mild to severe), limb malformations (e.g., bilateral symmetric tetraphocomelia or hypomelia due to mesomelic shortening), and craniofacial findings (e.g., microcephaly and cleft lip and/or palate), along with predisposition to cutaneous hemangioma, possibly cavernous hemangioma, cutaneous melanoma, and rhabdomyosarcoma. The pathogenesis of RBS relates to homozygous or compound heterozygous germline mutations in the ESCO2 gene, which eliminate the acetyltransferase activity of ESCO2 required for buildup and maintenance of the cohesin complex, leading to impaired gene expression, ribosomal RNA production, nucleolar form and function, phosphorylation of S6K1, S6, and 4EBP1 (which causes mTOR signaling inhibition and p53 pathway activation). Diagnosis of RBS is based on observation of a combination of clinical features (including growth retardation, symmetric mesomelic shortening of the limbs, and characteristic facies with microcephaly), cytogenetic analysis (for characteristic chromosomal abnormality of PCS and separation of the HR), and molecular identification of ESCO2 pathogenic variants. Treatment of RBS involves surgery and other standard procedures.
Disorders of bone and connective tissue
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Limb reduction defects may be extremely difficult to distinguish from each other. Some, in particular asymmetrical amputation defects associated with ‘amniotic constriction bands’, are likely to be non-genetic. Other asymmetrical defects may be associated with oesophageal, anal, cardiac, renal and vertebral abnormalities (the VATER or VACTERL association); again, the recurrence risk is low. Thalidomide was previously a major cause, but no other definite drug-induced defects of this type are known. The severe symmetrical limb reduction disorder Roberts syndrome, which shows a characteristic abnormality of chromosomal division, is autosomal recessive. Limb changes in Holt-Oram syndrome (autosomal dominant mutations in TBX5) can be very similar to those caused by thalidomide and may occur without accompanying cardiac defect.
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Differential diagnosis:Roberts syndrome (p. 467); Acheiropody: absence of hands and feet; can show more extensive reduction defects, involving forearm, elbow joint, fibula and distal third of the tibia; due to a deletion in the gene C7ORF2. Grebe dysplasia (p. 232); DK phocomelia syndrome (p. 519); femur-fibula-ulna syndrome (p. 488). Tetra-amelia: also shows multiple malformations, including cleft palate, aplasia of the peripheral pulmonary vessels, anal atresia, diaphragmatic defect, hypoplasia or aplasia of lung, kidneys, spleen, adrenal gland, uterus and ovaries. Recessive mutations in the gene WNT3 gene have been found. Fuhrmann syndrome: milder disorder which shows bowed femora, aplastic or hypoplastic fibulae, poly/oligo/syndactyly, dystrophic nails. Autosomal recessive, mutations in WNT7A have been found.
Emerging strategies to target the dysfunctional cohesin complex in cancer
Published in Expert Opinion on Therapeutic Targets, 2019
Konstantinos Mintzas, Michael Heuser
A series of developmental disorders, termed cohesinopathies, have been attributed to mutations in cohesin genes or their regulators. The Cornelia de Lange syndrome is a clinically heterogeneous disease typically associated with microcephaly, short stature, hypertrichosis, bone malformations and mental retardation with mutations described in the regulatory protein NIPBL and core proteins SMC1A, SMC3, RAD21 and STAG1 [23–27]. The pathology of the disease has been suggested to be linked to aberrant gene regulation attributed to dysfunctional cohesin. Roberts Syndrome, characterized by limb and facial abnormalities, and Warsaw breakage syndrome, characterized by intellectual disability, impaired growth, and heart malformations, are two other cohesinopathies attributed to mutations on the regulatory proteins ESCO2 and DDX11, respectively[28].
Severe Craniofacial Involvement due to Amniotic Band Sequence
Published in Fetal and Pediatric Pathology, 2018
Luis Eduardo Becerra-Solano, Gema Castañeda-Cisneros, Jorge Roman Corona-Rivera, Manuel Díaz-Rodríguez, Luis Eduardo Figuera, Eunice López-Muñoz, José Antonio Nastasi-Catanese, José Jesús Toscano-Flores, María de Lourdes Ramírez-Dueñas, José Elias García-Ortíz
In the differential diagnosis of DABS with craniofacial defects, Adams-Oliver syndrome (OMIM 100300, gene ARHGAP31; OMIM 616028, gene NOTCH1; OMIM 614219, gene DOCK6) must be considered and ruled out; this condition is a heterogeneous entity characterized by aplasia cutis, bilateral involvement in the upper and lower limbs and autosomal dominant inheritance. Roberts syndrome (OMIM 268300) characterized by long-bone deficiency, cleft lip and palate, with autosomal recessive inheritance caused by mutation of the ESCO2 gene must also be considered and ruled out. Neither of these syndromes presents with the typical ring scar in the limbs.
Acute Transient Oculomotor Nerve Palsy from Presumed Cavernous Angioma in an Infant
Published in Neuro-Ophthalmology, 2018
Sonya T. Blizzard, Megan E. Collins, Neil R. Miller
This is the first published report of a presumed cavernous angioma involving the subarachnoid portion of the oculomotor nerve in an infant. Cavernous angiomas of the cranial nerves, especially those involving the ocular motor nerves, are extremely rare. In a review of 58 cranial nerve angiomas,1 21 were located within one of the optic nerves or chiasm, 26 involved the facial or auditory nerves, five cases involved the oculomotor nerve, three cases involved the trochlear nerve, one case involved the trigeminal nerve, and one case involved the hypoglossal nerve. There are a total of nine cases involving the oculomotor nerve in the literature. Five presented with sudden onset of a third nerve paresis and occurred without precipitating factors in adolescent or adult males (Table 1).2,3,5,8 The acute clinical presentation of these cases was thought to be due to hemorrhage within the lesion. The remaining four cases presented with slowly progressive symptoms and signs. One of these cases was a young man who experienced progressive third nerve dysfunction over a 6-month period.6 Another patient was a young woman with galactorrhea, amenorrhea, and a visual field defect from compression of the pituitary stalk and optic chiasm by the lesion.4 The third patient presented with chronic facial pain that had no clear relationship to the lesion.7 The final patient was a 71-year-old man with a 2-month history of a progressive oculomotor nerve paresis.9 Interestingly, two of the reported cases occurred in patients with Roberts Syndrome,2,5 a rare genetic condition associated with craniofacial and ocular anomalies, mental retardation and phocomyelia of the limbs.