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At a glance

A rare syndrome with craniofacial anomalies (hypoplastic maxilla, slanted palpebral fissures), hirsutism and complex multiple malformations which affect limbs (broad thumbs and toes), cardiac, genitourinary and respiratory system. Intellectual disability and growth retardation.

Synonyms

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

History

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

Incidence

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

Genetic inheritance

Autosomal dominant; however, most cases are sporadic.

Pathophysiology

The gene most frequently involved is cyclic-AMP-regulated enhancer binding protein (CREBBP) located on chromosome 16p13.3. Alterations in the E1A-binding protein p300 (EP300) have also been detected.

Diagnosis

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

Clinical aspects

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 defects), 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) but also leukemia. Children survive well into adulthood (>90%).

Precautions before anesthesia

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

Anesthetic considerations

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 is 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.

Pharmacological implications

Avoid cardiodepressive drugs and use prophylactic antibiotics in case of cardiac disease. Avoid parasympatholytic medications in patient with glaucoma. Aminoglycoside agents can be used; however, the dose must be calculated according to ...

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