Mobius Syndrome Clinical Presentation

Because of the early age at which Möbius syndrome becomes obvious, parents or other caretakers generally bring infant patients to medical attention. Facial and ocular symptoms are usually the presenting problems. ^[22]

Facial paralysis

Facial diplegia is the most noticeable symptom. This may be observed soon after birth, with incomplete eyelid closure during sleep, drooling, and difficulty sucking. ^[23] On occasion, the facial paralysis is not noticed for a few weeks or months, until the infant's inability to smile or the lack of facial movement with crying arouses the parents' concern.

Because of the patient’s facial and forehead immobility, the skin appears to be devoid of wrinkles. In some cases, only a slight diminution in the width of the palpebral fissures during sleep may be noted.

An inability to close the mouth is the rule. Undue prominence of the upper lip is a striking feature. In adults, the lower lip is usually everted and prominent. Food is apt to lodge in the cheeks when the patient eats.

Speech problems are reported in 76-90% of patients with Möbius syndrome. ^[24] Speech is usually indistinct because of the patient's inability to close his or her lips and make labial sounds. In some cases, speech impairment may be severe.

Hypogonadism

The association of Möbius syndrome with anosmia and hypogonadotrophic hypogonadism (Kallmann syndrome) or with hypogonadism alone has been reported. ^[25]

Autism

Möbius syndrome has been associated with autistic behavior. In 1989, Gillberg and Steffenburg reported that autistic symptoms are present in 30–40% of children and young adults with Möbius syndrome. ^[26] This has been confirmed in other series. ^[27]

Intelligence

The patient’s intelligence is usually normal, but mild mental retardation is thought to occur in approximately 10–15% of patients. ^[24] Many authors report that without formal testing, intelligence may be underestimated because of the patient’s facial appearance.

In a study involving extensive neuropsychological testing, Verzijl et al found no diminishment in intellect, attention span, or memory in 12 adults with Möbius syndrome, compared with the healthy population. ^[28] However, because none of the patients in the study had autism, these results could not be extrapolated to patients with a combination of Möbius syndrome and autism.

Other Abnormalities

Among the less common anomalies in Möbius syndrome are dextrocardia, arthrogryposis multiplex congenita, and the Klippel-Feil anomaly. A case of Möbius syndrome presenting with congenital bilateral vocal cord paralysis was reported by Kanemoto in 2007. ^[21]

Physical findings entirely depend on the case definition of Möbius syndrome. By using the most commonly accepted definition, the typical phenotypic appearance is an immobile facial appearance with various gaze palsies.

Facial nerve palsy is usually bilateral and incomplete, involving either the upper or the lower portion of the face. The resulting masklike face makes this diagnosis obvious upon initial inspection. The flattened facial expression, which deprives patients of the ability to convey emotions, causes patients to have difficulties in relating to other persons.

External ocular palsies, including ptosis, accompany the facial diplegia in approximately 80% of patients. These extraocular abnormalities may be single or multiple.

Secondary to the feebleness of blinking and the incomplete closure of the eyelids during sleep, the cornea and conjunctiva are poorly protected. Recurrent or chronic conjunctivitis frequently occurs. Corneal opacities are unusual but sometimes are observed in adults.

Bulbar weakness may be mild or severe. Dysphagia, caused by paresis of CNs IX and X, is common.

Skin abnormalities have been associated with the Möbius syndrome, including café-au-lait pigmentation, webbing of the axilla, and an absence of subcutaneous tissue.

Masticatory muscles are rarely affected. Instances of bilateral paresis of the soft palate and scattered instances of dysphagia (some of which resolve in infancy) have been reported. Infantile nasal regurgitation has been described in the literature.

In one study, the majority of 17 patients with Möbius syndrome had hearing in the normal range, with no consistent abnormal pattern present in the remaining patients. ^[29]

Abducens nerve palsies

Abducens nerve palsies are reported in approximately 75% of patients and are some of the most characteristic features of the syndrome. These palsies are characterized as follows in Möbius syndrome:

• Most are bilateral and usually complete

• Abducens paralysis is the only ocular palsy in approximately 50% of patients

• Affected children may be born with marked internal strabismus

• Ophthalmoplegia may be partial or complete

• Lateral gaze paralysis, which indicates medial longitudinal fascicular involvement, is often present

Hypoglossal nerve involvement

The hypoglossal nerve is the third most commonly affected cranial nerve (CN) and is involved in approximately 25% of reported cases. ^[23] Involvement of the hypoglossal nerves often leads to atrophy of the tongue. Patients may be unable to protrude their tongue beyond their lips because of this weakness. This involvement may result in paralysis and hypoplasia of the tongue, or fasciculations may be seen as a result of hypoglossal denervation. The ocular muscles are always involved when the tongue is affected.

Brachial malformation

Brachial malformation is common and can involve the following:

• It occasionally involves the arm, whereas the hand is always affected

• Reports include congenital amputation of the hand and clubhand

• In some cases, the affected hand is smaller than the other hand

• Syndactyly is not uncommon, and brachydactyly is frequently reported

• Other abnormalities in the upper extremities include finger webbing and an absence or hypoplasia of the radius, ulna, metacarpal, or phalanx

• Clubfoot, frequently bilateral, occurs in almost one third of patients; the deformity is usually correctable with surgery

Musculoskeletal abnormalities

Musculoskeletal abnormalities occur in one third or more of patients with Möbius syndrome. These anomalies may include the following:

• Talipes equinovarus

• Brachydactyly

• Syndactyly

• Congenital amputations (see the image below)

• Arthrogryposis

• Smallness of limbs

• Occasionally, hypoplasia or absence of the pectoralis major muscles (Poland anomaly)

  Autopsy photograph of a 3-month-old child with Möbius syndrome who died unexpectedly demonstrates congenital amputation of the left hand at the wrist.

  View Media Gallery

The Poland anomaly, first associated with Möbius syndrome in 1973, ^[5] is generally unilateral and is associated with mammary hypoplasia of the same side.

An estimated 15% of patients with Möbius syndrome have missing truncal muscle groups, including the pectoralis or trapezius muscles. Other muscle groups that may be aplastic or hypoplastic include the latissimus dorsi, external abdominal muscles, serratus anterior, and intercostal muscles.

Orofacial abnormalities

Numerous orofacial abnormalities are present in Möbius syndrome. In several cases, the root of the nose has been described as broad and rather flat. Bilateral epicanthus has been reported, and scattered instances of ear deformities have been described (usually bilateral and confined to the lobe). An arched palate and a bifid uvula have been described, as have microglossia, microstomia, micrognathia, teeth and jaw malformations, and hypertelorism.

Complications include facial movement, speech difficulties, musculoskeletal and orthopedic manifestations, swallowing/feeding, visual tracking, and chronic conjunctivitis.