CLINICAL CHARACTERISTICS

HYAL2 deficiency is characterized by cardiac anomalies, cleft lip and palate (unilateral or bilateral), ophthalmic findings (including mild-to-severe myopia up to −16.75 diopters and increased risk of retinal detachment), hearing loss (typically conductive), and skeletal findings (including pectus excavatum and digital anomalies). Intellect is typically normal. To date, 17 individuals from seven families have been reported with HYAL2 deficiency.

DIAGNOSIS/TESTING: The diagnosis of HYAL2 deficiency is established in a proband with suggestive findings and biallelic pathogenic variants in identified by molecular genetic testing.

MANAGEMENT

There is no cure for HYAL2 deficiency. Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This can include care by specialists in pediatric cardiology and cardiac surgery and a multidisciplinary craniofacial team to coordinate timing and type of surgical interventions, manage issues with feeding and nutrition, and work with speech-language pathologists (regarding speech and communication issues) and audiologists (regarding hearing loss). Members of the multidisciplinary care team will recommend intervals to monitor existing manifestations and the individual's response to supportive care.

GENETIC COUNSELING

HYAL2 deficiency is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the pathogenic variants have been identified in an affected family member, carrier testing for relatives at risk and prenatal and preimplantation genetic testing are possible.