Clinical characteristics: ROR2-related Robinow syndrome is characterized by distinctive craniofacial features, skeletal abnormalities, and other anomalies. Craniofacial features include macrocephaly, broad prominent forehead, low-set ears, ocular hypertelorism, prominent eyes, midface hypoplasia, short upturned nose with depressed nasal bridge and flared nostrils, large and triangular mouth with exposed incisors and upper gums, gum hypertrophy, misaligned teeth, ankyloglossia, and micrognathia. Skeletal abnormalities include short stature, mesomelic or acromesomelic limb shortening, hemivertebrae with fusion of thoracic vertebrae, and brachydactyly. Other common features include micropenis with or without cryptorchidism in males and reduced clitoral size and hypoplasia of the labia majora in females, renal tract abnormalities, and nail hypoplasia or dystrophy. The disorder is recognizable at birth or in early childhood.
Diagnosis/testing: The diagnosis of ROR2-related Robinow syndrome is established in a proband with typical suggestive findings and biallelic ROR2 pathogenic variants identified on molecular genetic testing.
Management: Treatment of manifestations: Corrective surgery for limb and spine defects and for facial abnormalities; orthodontic treatment as needed; surgery for males with scrotal transposition as needed; hormone therapy as needed for the treatment of micropenis.
Genetic counseling: ROR2-related Robinow syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected with Robinow syndrome, a 50% chance of being a heterozygote (carrier) and usually asymptomatic, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members, prenatal diagnosis for pregnancies at increased risk, and preimplantation genetic testing are possible when the ROR2 pathogenic variants have been identified in the family.
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