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To date 46 cases have been described, less than half of which were molecularly confirmed as carrying a heterozygous pathogenic variation in ASXL1.

Bohring-Opitz syndrome (BOS) is characterized by IUGR, severe neonatal feeding difficulties, and microcephaly/trigonocephaly, cleft lip/palate and hirsutism. Facial dysmorphism is characterized by glabellar/frontal nevus flammeus, synophrys, proptosis, hypertelorism, depressed wide nasal bridge, anteverted nares, full cheeks, and micrognathia. The posture of upper limbs, common in all patients at birth, is characterized by internal rotation of the shoulders, flexion of the elbows, ulnar deviation of wrists and/or metacarpophalangeal joints. Most patients exhibit truncal hypotonia and hypertonic extremities at birth. Seizures and obstructive sleep apnea/sleep disturbances can occur during infancy. Other abnormalities can involve the following organs: brain (corpus callosum defects), eyes (retinal and optic nerve abnormalities, high myopia), heart (bradycardia, septal defect), gastrointestinal tract (cycling emesis, gastroesophageal reflux disease) as well as the joints (contractures, congenital hip/radial head dislocations).

BOS is due to a heterozygous pathogenic variation in ASXL1 (20q11.21), which acts as a chromatin modulator.

Clinical diagnosis can be confirmed by sequencing of ASXL1 or by intellectual disability-related next generation sequencing panel including the gene. If sequencing is negative, multiplex ligation-dependent probe amplification may be used.

A BOS-like phenotype related to KLHL7 has been described which has several features in common with BOS (including a similar upper limb posture) but is clinically distinguished by the absence of trigonocephaly, synophrys, high myopia and cycling emesis. Other diseases sharing several features with BOS but lacking the BOS posture include C syndrome, Shashi-Pena syndrome, Bainbridge-Ropers syndrome and Cornelia de Lange syndrome.

Prenatal diagnosis is possible on chorionic villi or amniotic fluid where the pathogenic variant has been previously identified in the family. Prenatal genetic counseling should therefore be offered to parents of patients with ASXL1 variants to discuss the genetic risks and reproductive options.

The disorder is autosomal dominant; however, most cases are de novo. Genetic counseling should be offered to all at-risk couples since germinal mosaicism may occur.

Management requires an early multidisciplinary approach. Seizures are drug-responsive. An increased risk of Wilms tumor is reported. An abdominal ultrasound every 3-4 months is suggested in the first 8 years of life.

The rate of infant mortality is high. In patients who survive infancy, feeding difficulties and recurrent infections become less severe. Older patients may have some purposeful limb movements, however, their resting state returns to BOS posture. Intellectual disability ranges from severe to profound.