Schilbach-Rott Syndrome

Description

Schilbach-Rott syndrome is an autosomal dominant disorder characterized by hypotelorism, epicanthal folds, cleft palate, dysmorphic facies, and hypospadias in males. The phenotype is variable; mild mental retardation has been reported (summary by Shkalim et al., 2009).

Clinical Features

In 10 persons over 5 generations of a family, Schilbach and Rott (1988) found ocular hypotelorism, submucosal cleft palate, and, in males, hypospadias. Other anomalies were blepharophimosis, upslant of palpebral fissures, and a tendency to cutaneous syndactyly of fingers 3 and 4 and toes 2 and 3. One instance of male-to-male transmission was reported in earlier generations in which hypotelorism was said to have been present but was not documented by examination or by photographs.

Joss et al. (2002) described 2 brothers with cleft palate and facial appearance closely resembling the cases described by Schilbach and Rott (1988). One had hypospadias and learning disability and, like his mother, was of short stature.

Becerra-Solano et al. (2007) reported a Mexican father and son with Schilbach-Rott syndrome. The 3.5-year-old son had low Apgar scores at birth along with central cleft palate, hypospadias, and inguinal hernia. He later exhibited delayed psychomotor development. Dysmorphic features included brachycephaly with prominent metopic ridge, right ptosis, blepharophimosis, epicanthal folds, hypotelorism, small nose with high bridge, anteverted small ears with attached lobules, and short neck. His father had similar features without hypospadias. Both individuals also had microcephaly. Becerra-Solano et al. (2007) suggested autosomal dominant inheritance.

De Carvalho et al. (2008) reported a 4-year-old Brazilian girl with blepharophimosis, long face, broad forehead with a high anterior hairline, anteverted and prominent ears, malar hypoplasia, a broad nasal tip and columella, deeply grooved philtrum, small mouth, thin lips, and a long chin. She also had a broad thorax with a pectus carinatum, long and tapering fingers and toes, bilateral clinodactyly of the fourth and fifth fingers, and long, narrow great toes. Expressive language development was delayed. De Carvalho et al. (2008) concluded that the disorder was most similar to that described by Schilbach and Rott (1988), which could also be referred to as the blepharofacioskeletal syndrome (BRSS).

Shkalim et al. (2009) reported a Jewish family of Turkish-Libyan descent in which a father and his 2 offspring, a boy and a girl, had features most reminiscent of Schilbach-Rott syndrome. The proband was a 20-year-old woman, 1 of triplets, who had mild mental retardation with attention deficit-hyperactivity disorder and a distinctive facial appearance. Features included marked hypotelorism, small downslanting palpebral fissures, epicanthal folds, asymmetric facies, low-set, posteriorly angulated, and 'crumpled' small ears, high nasal bridge, elongated and asymmetric nose, elongated midface, small mouth, crowded teeth, and cleft palate. Brain MRI was normal. Her similarly affected brother, 1 of the triplets, had a similar facial appearance and mild cognitive defects. Their father left school after sixth grade and was a factory worker. He had facial asymmetry, hypotelorism, posterior angulation of the ears, high nasal bridge, prominent asymmetric nose, long columella, small mouth, and high-arched palate. Shkalim et al. (2009) commented on the phenotypic similarities to holoprosencephaly (HPE; 236100), but concluded that the disorder most resembled Schilbach-Rott syndrome. Array CGH did not reveal any putative pathogenic changes, and molecular analysis excluded mutations in the SEPT9 (604061), SHH (600725), and TWIST (601622) genes.

Inheritance

The families described by Schilbach and Rott (1988) and Shkalim et al. (2009) supported autosomal dominant inheritance.