Resident Detroit Medical Center Detroit, Michigan, United States
Case Diagnosis: Yuan-Harel-Lupski syndrome (YUHAL) Syndrome
Case Description: Yuan-Harel-Lupski (YUHAL) syndrome is a complex neurodevelopmental disorder characterized by global developmental delay and peripheral neuropathy. YUHAL syndrome is caused by a contiguous gene duplication of chromosome 17p12-p11.2 including the PMP22 and RAI1 genes. The disorder comprises a combination of features from Charcot-Marie-Tooth disease type 1A which results from duplication of the PMP22 gene on 17p12, and Potocki-Lupski syndrome, which results from duplication of the RAI1 gene on 17p11.2. The phenotypical presentation of YUHAL syndrome tends to be more severe than having either gene mutation alone and involves features of both peripheral and central neuropathy.
Discussions: The patient is a 47-year-old female who presented with concerns for an extensive history of developmental delays, congenital camptodactyly, psychiatric concerns, and unusual facial features. Her symptoms presented in infancy, specifically including weak muscle tone, inadequate weight gain, language and motor skills, strabismus, triangular face, loss of sensation and atrophy in lower extremities, and clubfoot. She also presented with severe nourishment and spastic gait hindering her ability to complete activities of daily living. Children known to have this duplication usually do not reach developmental milestones on time and may require therapies and/or additional help in school. Although behavioral concerns are common in YUHAL syndrome, its rarity led to a delay in diagnosis until adulthood when she presented to our clinic. She was misdiagnosed with schizophrenia and an intellectual disability in her past.
Conclusions: Due to the prevalence of YUHAL Syndrome being less than one in a million and only having under 30 cases ever recorded in medical literature, there are no specific clinical criteria, and any reported cases are augmentative to the current understanding of the syndrome. Similar presentations should warrant future clinicians to consider Yuan-Harel-Lupski syndrome as a differential diagnosis.
