Atypical presentation of a case with Noonan syndrome with multiple lentigines

We present the case of a 25-year-old man experiencing severe pain in his feet and hands, accompanied by hypermobility in small and ankle joints, as well as hyperelastic skin with atypical scarring. Papular nodes were observed on his hands, with multiple lentigines scattered across his body and face. Recurrent leg edema was also reported. Additionally, the patient had keratoconus and congenital cataract, along with a childhood history of motor delay, dyslexia, and ADHD, without intellectual disability. He is the only child of a Gambian father and an Eastern-European mother, the latter sharing the hypermobility trait and suffering from hypertrophic cardiomyopathy.
Exome sequencing revealed a pathogenic heterozygous variant in PTPN11, consistent with Noonan syndrome with multiple lentigines, formerly known as Leopard syndrome. However, while lentigines supported this diagnosis, some symptoms such as hypermobility, keratoconus, and cataract are uncommon in this syndrome. Moreover, the patient lacked typical facial features associated with Noonan syndrome (hypertelorism, downslanting palpebral fissures, low set ears) but exhibited upslanting palpebral fissures and hypotelorism. Facial image analysis using GestaltMatcher surprisingly still suggested Noonan syndrome on the 12th rank.
In summary, this patient's presentation is clinically atypical. While lentigines and the mother's hypertrophic cardiomyopathy align with the diagnosis, other typical features are absent, and there are additional symptoms unusual for Noonan syndrome with multiple lentigines. The discrepancy in facial features may be attributed to mixed ethnicity, or suggesting a potential dual diagnosis. This case emphasizes the necessity of a comprehensive, multidisciplinary approach, integrating molecular genetics and cutting-edge technologies like AI, and highlights the challenge of ethnic variation in symptomatology.