Teebi-Hypertelorismus syndrome Q87.-

Teebi 1987

Teebi hypertelorism syndrome (THS; OMIM 145420) is a very rare autosomal dominant dysplasia syndrome characterized by a prominent forehead, possibly with a frontal tapered hairline (see below pointed hairline), hypertelorism, exophthalmos, downward sloping palpebral fissures, a flat nasal bridge, a broad nasal tip, a long philtrum, milk teeth, a thin upper lip, an inverted lower lip, a small possibly notched chin, low-set ears, preauricular fistulas, a short neck, a slightly hollow back, an umbilical hernia, clinodactyly of the fifth finger with slight radial deviation of the distal phalanges of the middle fingers, a slight pes adductus, an ectopic kidney, and normal psychomotor development.

Some cases of THS can be traced back to SPECC1L variants.

Other cases leading to the THS phenotype are characterized by a heterozygous CDH11 missense variant. An immunohistochemical study shows that CDH11 is highly expressed in human facial mesenchyme. Characteristic features of this cohort include a flat nasal root and heart and umbilical cord defects. These features differentiated the CDH11 phenotype from the SPECC1L-related hypertelorism syndrome observed.

These results indicate that heterozygous variants in CDH11 that decrease cell-cell adhesion and increase cell migration behavior cause a form of THS termed CDH11-related THS. The symptoms of this variant in detail:

All patients of the CDH11 phenotype showed typical craniofacial features of DBS in a larger collective (Li D et al. 2021). The defining feature of ocular hypertelorism was observed in all affected individuals, with a broad or high forehead in 95%; (some with a large anterior fontanel), thick and/or broad eyebrows in 89%, a flat nasal root in 68%, a broad nasal tip in 95% and a short nose in 79% of affected individuals. Similarly, a thin upper lip was frequently observed in 84%, a small chin with horizontal crease in 84% and a high palate or cleft palate in 68%, while some facial dysmorphisms were less common, including proptosis (26%), ptosis (26%), an inverted lower lip (37%), small teeth (16%) and delayed tooth eruption (16%). Occasional limb anomalies, including tapered fingers, short terminal phalanges, broad thumbs/large toes, small hands/feet, long/short toes, bulbous toe tips, broad feet and clinodactyly of the fifth finger/toe, were observed in about 50% of affected individuals. Developmental delay and intellectual disability varied in 37% of those affected, ranging from a very mild speech delay in five individuals to a global delay. Behavioral disorders, i.e. autism and attention-deficit/hyperactivity disorder (ADHD), were only diagnosed in some relatives. 63% of those affected showed normal overall development (Li D et al. 2021)

1. Han XD et al (2006) Atrioventricular block and wiry hair in Teebi hypertelorism syndrome. Am J Med Genet A 140:1960-1964.
2. Li D et al. (2021) Pathogenic variants in CDH11 impair cell adhesion and cause Teebi hypertelorism syndrome. Hum Genet 140:1061-1076.
3. Teebi AS (1987) New autosomal dominant syndrome resembling craniofrontonasal dysplasia. Am J Med Genet 28:581-591
4. Tsai AC et al. (2002) Teebi hypertelorism syndrome: report of a family with previously unrecognized findings. Am J Med Genet 113:302-306.