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A rare syndrome with craniofacial anomalies and complex multiple malformations, including cardiac, digestive, and respiratory malformations.

Rubinstein Syndrome; Broad Thumbs and Great Toes, Characteristic Facies, and Mental Retardation Syndrome; Broad Thumbs-Hallux Syndrome.

First described in 1963 by Jack Herbert Rubinstein, an American pediatrician and Hooshang Taybi, an American pediatric radiologist.

Rare (less than 600 cases have been described); usually sporadic; 1:125,000 live births. More frequent in patients with mental retardation.

Autosomal dominant; however, most cases are sporadic.

Caused by mutation in the gene encoding the transcriptional coactivator CREB-binding protein located on 16p13.3. Involved in transcription regulation, chromatin remodeling, and the integration of several signal transduction pathways.

Clinical: association of mental retardation (100%), characteristic facies (100%), broad thumbs (100%), hallux (50%), and other malformations.

Progressive onset of the disease is usual and characteristic facies is observed later in infancy. Other clinical features include short stature (94%), microcephaly (84%) with micrognathia (100%), and various defects: cranial (frontal bossing, large fontanel, narrow mouth and palate, choanal atresia), ear (low-set ears, hearing loss), eyes (heavy eyebrows, long eyelashes, ptosis, glaucoma, coloboma, cataract epicanthal folds), heart (33%) (patent ductus arteriosus, atrial or ventricular defect), genitourinary (cryptorchism, hypospadias and renal defect), skin (keloid scars, hemangioma, café-au-lait spots, hirsutism, nevus flammeus), neurological (corpus callosum agenesis, hypotonia, hyperreflexia, seizures), and orthopedic (scoliosis, spina occulta, pes planus, patellar dislocation, clinodactyly, syndactyly). Swallowing troubles and feeding difficulties are frequent, as are respiratory infection and asthma. There is an increased risk of tumor, mainly of neurological origin (neuroblastoma, meningioma).

Evaluate cardiac function (clinical, chest radiograph, echocardiography) and airway for the potential of difficult tracheal intubation (clinical, radiograph).

Pulmonary aspiration risks are significant as a consequence of gastrointestinal anomalies. Direct laryngoscopy and tracheal intubation may be difficult because of facial malformations. It is recommended to maintain spontaneous ventilation until the trachea is intubated and lung ventilation confirmed. A laryngeal mask airway and fiberoptic equipment might be required. Careful intraoperative positioning is necessary because of skeletal deformation. Nasal intubation and nasogastric tube should be performed with caution because of the presence of choanal atresia. Specific consideration will be directed by the cardiorespiratory problems.

Avoid cardiodepressive drugs and use prophylactic antibiotics in case of cardiopathy. Avoid parasympatholytic medications in patient with glaucoma. Aminoglycoside agents can be used, however the dose must be calculated according to the renal function. Various problems have been described with anesthetic drugs such as atropine, neostigmine, succinylcholine (arrhythmias), propofol, and isoflurane (delayed awakening). However, these problems are isolated cases.

Trisomy 13 syndrome: Characterized by central nervous system and craniofacial abnormalities, polydactyly, severe mental retardation, and congenital heart defects. Some clinical features include microcephaly, forehead bossing, microphthalmia, cleft lip/palate, camptodactyly, and capillary hemangiomas. Eighty percent of individual affected with this medical condition present with congenital heart defects.

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