Costello Syndrome

A syndrome characterized by postnatal growth deficiency, coarse facies, redundant skin on the neck, acanthosis nigricans, developmental delay, and papillomata.

(Figure)

Fasciocutaneoskeletal Syndrome; Mental Retardation Papillomata Syndrome.

Approximately 50 cases have been described in the literature.

Most likely autosomal dominant.

The abnormalities stem from abnormal development of ectodermal tissue, the mechanism of which is not understood. The responsible gene is located on 22q13.1. The etiology of Costello syndrome is unclear. Fibroblasts show increased proliferation, normal elastin gene expression, produce normal amounts of tropoelastin, and properly deposit an extracellular microfibrillar scaffold; however, the assembly of elastic fibers is defective secondary to rapid shedding of elastin binding proteins. This finding has been suggested to result from accumulation of chondroitin sulfate moieties, a phenomenon also found in Mucopolysaccharidosis.

Clinical recognition of the peculiar course of the disease, typical facies, and ectodermal involvement (loose and hyperpigmented skin).

Pregnancy is frequently complicated by polyhydramnios. Respiratory distress immediately after birth has been reported in a few patients. Characteristically, patients are born with increased birth weight and macrocephaly, which is followed by postnatal growth retardation and failure to thrive. Patients often require an enteral feeding tube because of oral motor apraxia and swallowing problems. This period is called the marasmic phase, which is followed by the pseudo-thesaurismotic phase that is characterized by a storage disease-like picture with macrocephaly, full cheeks, large mouth with thick lips, macroglossia, and gingival hyperplasia. The disease involves the head and neck (macrocephaly, coarse facies, strabismus, keratoconus, chorioretinal dystrophy, hypertelorism, epicanthal folds, downslanting palpebral fissures, low-set ears with fleshy earlobes and helices, depressed nasal bridge with bulbous nose and anteverted nostrils, full cheeks, micrognathia, retrognathia, large mouth with macroglossia, high arched palate, bifid uvula, abnormal teeth, short neck), the skeleton (short stature with adult height between 118 and 148 cm, barrel chest, pectus excavatum/ carinatum, scoliosis, broad hands and feet, limited extension in elbow and wrist, pes equinovarus, subluxation of hip and elbow, osteoporosis), the skin (redundant skin on hands and feet leading to deep palmar and plantar creases and ridges, acanthosis nigricans, hyperkeratosis, fine hair, papillomata [facial, laryngeal, axillary, abdominal, cubital, popliteal, anal], multiple pigmented nevi, capillary hemangiomata on the forehead), the central nervous system (developmental delay with an IQ between 47 and 85, speech development delay, seizures, mild brain atrophy, cerebellar atrophy, generalized ventricular dilatation [occasionally requiring ventriculoperitoneal shunting], muscular hypotonia or hypertonia), and the genital region (cryptorchidism, inguinal hernia). Cardiac abnormalities including hypertrophic cardiomyopathy, pulmonary stenosis, atrial and ventricular septal defects, and dysrhythmias have been described. Hepatosplenomegaly and umbilical hernias have been described in some patients. These patients have an increased risk for malignant solid tumors (up to 17% of patients), including neuroblastoma, rhabdomyosarcoma, and bladder carcinoma. Laryngeal web, crumpled vocal cords, and tracheoesophageal fistula have been described in one patient each. Abnormal glucose metabolism occurs occasionally. A study found low levels of growth hormone and reported good response to growth hormone therapy. Cardiac problems, failure to thrive, and pneumonia are the main reasons for early death.

Assess cardiac function and obtain an echocardiogram to exclude cardiac anomalies. Anticipate difficult airway management secondary to macroglossia, abnormal teeth, laryngeal anomalies, and short neck. Regular checks of perioperative glucose levels are recommended. Because these patients should undergo regular tumor screening, check the date and results of the last follow-up.

In one published case report, preoperative multiple atrial ectopic beats, gastrointestinal reflux, and thickened arytenoid folds were encountered. On the one hand, a rapid-sequence induction may be indicated because of gastroesophageal reflux. On the other hand, airway management may be difficult, so spontaneous ventilation should be maintained until the airway has been secured. It will therefore depend on the clinical situation, which problem will receive preference. Tracheobronchial secretions appear to be abundant and require repeated suctioning. Careful intraoperative positioning is needed because of limb deformities, osteoporosis, and a tendency to subluxations.

Subacute bacterial endocarditis prophylaxis may be required. Avoid neuromuscular blockers until the airway has been secured (except for rapid sequence induction).

Cantu Syndrome: A congenital multisystem syndrome involving neonatal macrosomia, cardiomegaly, osteodysplasia, and hypertrichosis.

Noonan Syndrome: A rare genetic disorder present at birth. Characterized by distinctive facial appearance, a broad or webbed neck, a low posterior hairline, and short stature. Micrognathia, kyphosis and/or scoliosis, and cardiac defects are present. Other features include coagulation disorders, platelet deficiencies, mild mental retardation, and cryptorchidism.

Reynolds Neri Hermann Syndrome: A rare syndrome characterized by postnatal growth retardation with cardiac defects (atrial septal defect, pulmonic stenosis) and craniofacial anomalies (facial features similar to Noonan syndrome). Other features include relative macrocephaly, micrognathia, high arched palate, splenomegaly, hypotonia or hypertonia, hydrocephalus and raised intracranial pressure, and brainstem atrophy (gait ataxia).

De Barsy Moens Diercks Syndrome (De Barsy Syndrome; Progeroid Syndrome of De Barsy; Corneal Clouding Cutis Laxa Mental Retardation Syndrome): Extremely rare disorder inherited as an autosomal recessive trait. The main characteristics are frontal bossing and large, prominent ears, athetosis, cornea clouding, hypotonia, hyperlaxity of the small joints, and/or short stature.