Cohen Syndrome

An inherited disorder characterized by hypotonia, obesity, prominent incisors, and nonprogressive psychomotor retardation.

Norio Syndrome; Pepper Syndrome; Hypotonia-Obesity-Prominent Incisors Syndrome; Obesity-Hypotonia Syndrome.

Approximately 100 cases have been described. An increased frequency has been reported in Finland and in the Ashkenazi Jewish population. Consanguinity is a known, but not constant risk factor. No sexual predilection.

Autosomal recessive. The mutation has been mapped to 8q22-q23.

The wide clinical variability of this disorder makes the diagnosis difficult, which is primarily based on the clinical findings of nonprogressive psychomotor retardation, microcephaly with characteristic facial appearance, early hypotonia, joint hyperextensibility, clumsiness, truncal obesity, mottled retina, and myopia in patients with isolated and intermittent neutropenia (<2 × 109/mm3). Because of the highly variable features, the diagnosis often is not made until late infancy or even childhood.

Pregnancy most often is uneventful and birth occurs at term, however, poor fetal movement and growth and oligohydramnios have been described in some patients. Poor feeding in the first year of life is common. The disease involves the head and neck (microcephaly, thick scalp hair, eyebrows and eyelashes, prominent nasal bridge and beak-shaped nose, maxillary hypoplasia, prominent incisors [more the result of short and thin upper lip, which becomes even more pronounced on smiling], micrognathia [usually mild], short, upturned philtrum, high narrow palate, open mouth appearance), the heart (mitral valve prolapse is common, but rarely of clinical significance, progressive left ventricular dysfunction may occur with increasing age), the eyes (wave-shaped, downward slanting palpebral fissures, progressive pigmentary retinopathy, chorioretinal dystrophy, optic atrophy, early myopia, strabismus, vision deteriorates with age and patients are severely handicapped by the fourth to fifth decade of life), the central nervous system (mental retardation, delayed motor milestones, seizures, generalized hypotonia), and the skeleton (short stature secondary to growth hormone deficiency, kyphoscoliosis often starting after puberty, joint hyperextensibility [particularly hands, feet, knees], cubiti valgi, genua valga, narrow hands and feet with slender fingers and toes, camptodactyly, shortened metatarsals). Other features may include low birth weight, transverse palmar creases, obesity (although less common than initially thought), generally cheerful, socially interactive and cooperative personality, delayed puberty, and mild-to-moderate neutropenia (78% of patients), which does not appear to predispose the patients to infection. Stridor occurs in about one fourth of patients and most often is a result of laryngomalacia. Vocal cord paralysis was responsible for tracheostomy for more than 1 year in one patient. Lifespan appears to be normal.

A detailed cardiovascular evaluation should be performed (clinically, electrocardiography, echocardiography). Evaluate head and neck anatomy with regard to airway management because of craniofacial anomalies and prominent teeth (radiographs may be required). Evaluate neurologic status (clinically, computed tomography scans or magnetic resonance imaging, electroencephalography). Obtain a complete blood count with white cell differentiation (neutropenia).

The combination of prominent incisors, maxillary hypoplasia, and micrognathia suggests direct laryngoscopy and tracheal intubation may be difficult. Spontaneous ventilation should be maintained until the airway has been secured. Appropriate preoxygenation is recommended secondary to obesity and possible difficult airway management. Regional anesthesia is not contraindicated, but should be expected to be difficult because of obesity and orthopedic features (e.g., kyphoscoliosis). Careful intraoperative positioning must be performed. Strict asepsis is needed because of neutropenia. Vascular access can be difficult secondary to obesity.

Subacute bacterial endocarditis prophylaxis may be required. Muscle relaxants should not be used until the airway has been secured. Consider the interaction of anesthetic drugs and antiepileptic treatment in patients with seizures.

Alström Syndrome: Inherited syndrome with diabetes mellitus, cardiac, hepatic, and renal involvement, and progressive visual and hearing loss.

Bardet-Biedl Syndrome: Mental retardation, pigmentary retinopathy, polydactyly, obesity, renal anomalies, and hypogenitalism.