Möbius syndrome associated with neurofibromatosis Type 1: A rare co-occurrence.

Möbius syndrome is a rare congenital disorder presenting with facial diplegia and horizontal gaze disturbance. Patients can have additional cranial nerve palsies and musculoskeletal deformities. Neurofibromatosis Type 1 is an uncommon neurocutaneous disorder. The only plausible link between these two disorders is autosomal dominant pattern of inheritance. Simultaneous occurrence of these two uncommon disorders has not been yet reported in literature, and it is the first case report to the best of our knowledge.

Introduction

Möbius syndrome is a rare congenital disorder and was first reported in 1888. Patients with Möbius syndrome have facial diplegia, horizontal gaze disturbance and may have additional cranial nerve palsies. Neurofibromatosis Type 1 (NF1) or von Recklinghausen disease is the most common neurocutaneous syndrome, occurring nearly in 1 in 3500 people. NF1 is characterized by the development of multiple café-au-lait spots, neurofibromas and axillary freckling. To the best of our knowledge, this rare concurrent occurrence of Möbius and NF1 has not been yet reported in literature.

Case Report

An 11-year-old boy presented to us with inward deviation of both eyes since birth and incomplete closure of eyelids during sleep. There was no history of diplopia, dysarthria or dysphagia. He was first in birth order, born out of nonconsanguineous marriage with normal developmental milestones. There was no history suggestive of birth asphyxia. No history of intake of any drugs during pregnancy by the mother except for iron and folic acid tablets. His father had multiple café-au-lait spots, axillary/inguinal freckling and hypertension. His other two siblings were normal. His physical examination showed multiple café-au-lait spots [Figure 1a–c] and axillary freckling. The patient didn’t have Lisch nodules or any musculoskeletal abnormalities. Neurologic examination revealed bilaterally normal fundi, bilaterally medially deviated eye balls, facial diplegia and tongue atrophy [Figure 2a and b]. Rest of the cranial nerves were normal. His motor and sensory systems examination were within normal limits. His cranial magnetic resonance imaging didn’t show any abnormality of brainstem [Figure 3].

Figure 1

Café-au-lait spots on shoulder (a), thigh (b), ankle (c)

Figure 2

Bilaterally medially deviated eyeballs (a), and tongue atrophy (b)

Figure 3

Cranial magnetic resonance imaging (a) Axial T2, (b) Axial FLAIR, (c) Sagittal T1 showing normal brainstem

Discussion

Möbius syndrome is a rare congenital disorder and was first reported in 1888 by Paul Julius Möbius. The definition was extended by Henderson who also included patients with congenital unilateral facial palsy.[1] Patients with Möbius syndrome have facial diplegia, horizontal gaze disturbance and may have additional cranial nerve palsies. Möbius syndrome results from an underdevelopment of VI and VII cranial nerves. People with Möbius syndrome are born with facial paralysis and inability to move their eyes laterally. Multiple cranial nerves can get affected with cranial nerves VI, VII, and XII being affected more commonly. It has been estimated that the incidence of Möbius syndrome would be between 2 and 20 per million live births.[2] Most of the cases are sporadic, but a few cases with autosomal dominant, autosomal recessive, and X-linked recessive inheritance pattern have also been reported.[3456] It is an uncommon disorder with many unanswered questions regarding its etiology and pathogenesis. It has been associated with multifactorial causative factors including vascular compromise in the brain during prenatal period and agenesis or hypoplasia of the cranial nerve nuclei during the process of fetal development.[7] A higher frequency of occurrence is seen with the use of cocaine, thalidomide and prostaglandins during pregnancy.[8]

In our patient in addition to Möbius syndrome, he also had NF1 meeting diagnostic criteria. NF1 is known as von Recklinghausen disease. It has autosomal dominant inheritance with complete penetrance and variable expression. It has an incidence of 1 in 3500 live births. Diagnostic criteria include neurofibromas, café-au-lait spots, skinfold freckling, skeletal dysplasia, lisch nodules, and optic gliomas.

Both, NF1 and Möbius syndromes are uncommon disorders. The only common thread linking the two is an autosomal dominant pattern of inheritance. To the best of our knowledge, it is a rare co-occurrence of two rare and varied disorders.