Manitoba Oculotrichoanal (MOTA) Syndrome
Ocular abnormalities include ipsilateral colobomas of the upper eyelid (sometimes referred to as a Tessier number 10 cleft), corneopalpebral synechiae (i.e., adhesions between the eyelids and the cornea, also known as abortive cryptophthalmos), and microphthalmia/anophthalmia and/or cryptophthalmos. Anomalies may be unilateral or bilateral; the severity may differ between the two eyes.
Visual impairment may result directly from the ocular malformations or indirectly from exposure keratopathy. The long-term visual outcome depends on the severity of the ocular malformations and is poor for individuals with bilateral complete cryptophthalmos. In those with milder ocular malformations, such as upper eyelid colobomas, vision is typically intact.
Corneal clouding was described in one individual.
Anal anomalies include anal stenosis and/or anteriorly placed anus. No associated anomalies of the sacrum, vertebrae, or tethered cord have been reported. No affected individuals have had refractory constipation, fecal incontinence, or procedure-related stenosis or fistula.
Characteristic facial features include widely spaced eyes; an aberrant anterior hairline extending down to the ipsilateral eye (unilateral or bilateral) that is often wedge-shaped but may also resemble a thin stripe or appear tongue-shaped; ipsilateral absent or interrupted eyebrow; and a broad nose or notched or bifid nasal tip.
Omphalocele or umbilical hernia has been reported in approximately one third of affected individuals. Conservative management or surgical intervention for omphalocele or umbilical hernia is usually well tolerated, and outcomes are excellent. Long-term intestinal complications have not been described.
Other. Additional findings have been reported: renal pelviectasis, renal dysplasia, hydrometrocolpos and vaginal atresia, cutaneous syndactyly, and additional dysmorphic features (e.g., high forehead with a frontal upsweep of hair, dysplastic ears, maxillary hypoplasia, underdeveloped ala nasi, short philtrum, thin upper lip, and relative microstomia) [Slavotinek et al 2011, Mitter et al 2012, Nathanson et al 2013]. One infant born with right unilateral dysplastic kidney had Cohen grade IV anterior glottic web (75% occlusion), grade I subglottic stenosis (40% stenosis), and aphonia [Dahlquist et al 2024].
Growth and development. Individuals with MOTA syndrome assessed at various ages appear generally healthy with age-appropriate growth and cognition. Motor, social, and speech-language skills are typically normal, although development may be influenced by the presence of severe eye defects that lead to visual impairment.
The manifestations and degree of severity vary even among affected members of the same family.
Bifid Nose with or without Anorectal and Renal Anomalies (BNAR) Syndrome
BNAR syndrome was described in ten individuals from three consanguineous families of Egyptian, Afghani, and Pakistani origin [Al-Gazali et al 2002, Alazami et al 2009]. Subsequently, biallelic FREM1 pathogenic variants have been reported in several additional individuals with this phenotype [Brischoux-Boucher et al 2020, Berrada et al 2023, Chen et al 2023].
Craniofacial features include broad and/or bifid nose (100%), widely spaced eyes, aberrant hairlines, and short and thick oral frenula. Some individuals have only been found to have a broad and/or bifid nose [Brischoux-Boucher et al 2020, Chen et al 2023]. Colobomas similar to MOTA syndrome have been described [Berrada et al 2023], but typically the eye manifestations of MOTA syndrome are absent.
Kidney malformations (e.g., bilateral renal agenesis, unilateral renal agenesis) have been found in around two thirds (8/12) of individuals evaluated, although not all individuals have had kidney ultrasound examination. Unilateral renal agenesis is the most common kidney malformation [Chen et al 2023].
Anorectal malformations (e.g., anteriorly placed anus, anal stenosis) is comparatively rare, found in 2/13 individuals evaluated.
Airway malformations have been reported in 2/8 individuals evaluated.