Michels syndrome (oculopalatoskeletal syndrome) was first described by Michel et al. in 1978 among four siblings exhibiting the classical triad of blepharophimosis, blepharoptosis and epicanthus inversus (BBE) in addition to a developmental anomaly of the anterior segment of the eye, a cleft lip and palate condition and some minor skeletal abnormalities. This is an autosomal recessive and can result from consanguinity. A total of 10 cases were reported by Cunnif and Jones in 1990, De La Paz et al. in 1991, Guion-Almeida and Rodini in 1995, Titomanlio et al. in 2005 and Leal and Baptista in 2007 worldwide. This is the eleventh case worldwide and the first report from India.
A 2-year, 7-month old girl was brought to our pediatric eye clinic with the complaint of inward deviation of the left eye since 6 months of age [Fig. 1 and 2]. She was the second child in a family of four, born to healthy first-degree consanguineous parents. She was a full term child with a birth weight of 3 kg. She had low APGAR scores and was hospitalized and placed in an incubator and recovered uneventfully post oxygen therapy on her first day of life. She was immediately noticed to have a cleft lip and palate (causing feeding difficulties), which were surgically repaired at 9 months. She had delayed developmental milestones evidenced by the inability to walk.
General examination at our facility revealed a child who was small for her age, weighing 10.3 kg, which was just below the 3rd centile. She had low set ears, broad hands, short fingers, and short broad feet [Fig. 3a–c].
She also had a surgically repaired cleft lip and palate with minimal scarring, mandibular hypoplasia, micrognathia, high arched brows, flattened superior orbital bridge, faint upper lid crease, a broad nasal bridge and an expressionless face [Fig. 1].
Her facial features included blepharophimosis (interpalpebral fissure height of 11 mm), blepharoptosis, epicanthus inversus and telecanthus (intercanthal distance of 35 mm and interpupillary distance of 50 mm). She had no lagophthalmos.
Her cleft lip and palate was hampering her speech. Her abdominal and other systems were normal. There were no hernias or diastases observed [Fig. 3d]. Muscle tone was normal.
Unaided visual acuity in right and left eye by Lea distance chart symbols was 20/160 and 20/200. She had pseudo-proptosis due to shallow orbits typically associated with craniosynostosis. There was esotropia of 50-55 prism diopters for both distance and near with dissociated vertical deviation (DVD) and inferior oblique muscle over action in both eyes. Her cycloplegic refraction in right and left respectively eye was +1.00 DS/−1.75 DC × 80° and + 1.00 DS/−2.50 DC × 60°.
She was diagnosed with Michels syndrome, V pattern esotropia and DVD. She was prescribed glasses and advised to undergo bilateral medial rectus recession (6 mm each eye) with inferior oblique muscle anterior transposition in both eyes. The postoperative outcome was good [Fig. 4 and 5].
The Online Mendelian Inheritance in Man (OMIM number 257920) tagged this rare disorder along with three others that are similar yet different as the Mingarelli, Malpeuch, Michels, Carnavale syndrome (3MC1 syndrome). The mutant gene called Mannan binding lectin serine protease 1 gene (MASP 1) encodes the MASP 1 enzyme to facilitate the lectin complement pathway to amplify its activation of an immune reaction in response to threatening stimuli. This gene is located on chromosome 3q27.3 and its mutation gives rise to anomalies in the embryonic craniofacial cartilage, heart, bronchi, kidney, and vertebral bodies called the 3MC1 syndrome. For the first time the fundamental role of the complement pathway in developmental processes in humans and in the origin of the 3MC1 syndrome is shown.
The main features of Michel's syndrome include the BBE triad, telecanthus and highly arched brows seen in up to 80%. Our proband shared these phenotypical traits with the other three syndromes of Malpeuch, Carnavale and Mingarelli, however she had low set ears and did not have skeletal defects as reported by Guion-Almeida and Rodini. She had neither the radioulnar synostosis nor the abdominal diastases as reported in the original Michels syndrome report. She had middle ear dysfunction indicating some hearing loss, as detailed in an audiometry test (tympanometry). Cleft lip and palate and postnatal growth deficiency are also consistent findings seen in 40-68% of cases of 3MC1. Rare features include anterior chamber defects, cardiac anomalies, accessory nipples, tuberous angioma of the thorax, caudal appendage, umbilical hernia (omphalocele) and diastasis recti seen in < 20-30% of cases of 3MC1 [Table 1]. Abdominal defects may be due to hypoplasia of parts of the abdominal muscles in these patients absent in our proband [Table 1 and Fig. 3d].
However, she shared many similar phenotypical traits with other reported cases of Michels syndrome exhibiting virtually all the reported features except for radioulnar synostosis and anterior chamber defects [Table 1]. This differentiates it from the 3MC1 syndromes. All 11 cases (including ours) consistently exhibit the BBE triad plus a cleft lip and palate. While the ears in the other three syndromes were large and fleshy, our proband exhibited low set ears. In addition in Mingarelli, the hearing is actually normal. Sometimes other skeletal defects in the form of spina bifida occulta, cranial asymmetry, abnormality of the occipital bone in addition to micrognathia are found. This was absent in our case (except for micrognathia), but has been reported in some previous reports of Michels syndrome. Some have large anterior fontanelles, severe axial dystonia poor speech, mild psychomotor retardation and a bilateral conductive hearing loss, which were all present in varying degrees in our patient. Leal and Baptista had reported a caudal appendage in three patients. Cases reported by Al Gazali et al. in 2007 can be distinguished from this case due to the presence of arachnodactyly, congenital heart disease, growth retardation, and early lethality, which is not typical in Michels syndrome. Table 2 compares all published cases, including ours. Expense was a limiting factor in conducting genetic and intelligence quotient tests, which may have helped to a great extent in making a clearer and distinct diagnosis.
This is the 11th case of Michels syndrome worldwide and the first documented case in India. Recognizing this rare condition will help ophthalmologists make a phenotypical diagnosis and will aid in the overall management of eye conditions and appropriate referral to pediatricians for systemic conditions.
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