Autosomal recessive disease. Severe midfacial and limb defects and birth length less than 37cm associated with stillborn or early infant death. Likely allelic with SC phocomelia syndrome (MIM.269000).

The rare, autosomal recessive Roberts syndrome (RBS) is characterized by tetraphocomelia, profound growth deficiency of prenatal onset, craniofacial anomalies, microcephaly, and mental deficiency.

Synopsis

 low birth weight
 birth length less than 40cm
 birth weight 1.5-2.2 kg
 severe prenatal growth deficiency
 failure to thrive
 mild-severe postnatal growth deficiency

 craniofacial anomalies

• microcephaly
• brachycephaly
• micrognathia
• malformed ears
• lobeless ears
• low-set ears
• posteriorly-angulated ears
• hypertelorism
• shallow orbits
• prominent eyes or exophtalmy
• bluish sclerae
• corneal clouding
• microphthalmia
• cataract
• lid coloboma
• thin nares
• hypoplastic nasal alae
• widened nasal bridge
• cleft lip
• cleft palate
• short neck
• nuchal cystic hygroma

 cardiovascular malformations

• atrial septal defect
• ventricular septal defect
• patent ductus arteriosus

 rudimentary gallbladder
 genitourinary anomalies

• accessory spleen
• hypospadias
• enlarged penis
• enlarged clitoris
• enlarged labia minora
• cryptorchidism
• bicornuate uterus
• multicystic kidneys
• horseshoe kidney

 skeletal and limb anomalies

• craniosynostosis
• hypomelia (more severe in upper limbs)
• phocomelia (tetraphocomelia)
• elbow contracture
• absence or reduction in length of humerus, radius, or ulna
• knee contracture
• absence or reduction in length of femur, tibia, or fibula
• wrist contracture
• syndactyly
• clinodactyly
• oligodactyly (ectrodactyly)
• ankle contracture
• talipes equinovalgus
• reduction in number of toes

 midfacial capillary hemangioma
 sparse hair
 silvery blonde scalp hair

 cerbral anomalies

• mental retardation
• frontal encephalocele
• hydrocephalus
• cranial nerve paralysis

 polyhydramnios

Cytogenetics

 premature separation of centromeric heterochromatin
 normal karyotype
 abnormal nuclear morphology

Etiology

 Roberts syndrome is caused by mutation in the ESCO2 gene (cohesion 1 homolog 2 gene) (MIM.609353)

• The protein product of the ESCO2 gene is required for the establishment of sister chromatid cohesion during S phase.

See also

 SC phocomelia