Comparison of hair manifestations in cardio‐facio‐cutaneous and Costello syndromes highlights the influence of the RAS pathway on hair growth

Abstract

Background Abnormal hair growth is a defining feature of RASopathies, syndromes caused by germline mutations in the RAS pathway. However, detailed hair manifestations and the mechanisms of altered hair growth in RASopathies are poorly delineated. Objectives To identify distinguishing clinical features and investigate how the RAS pathway influences hair growth by performing a systematic and detailed side‐by‐side comparison of hair manifestations in cardio‐facio‐cutaneous syndrome (CFCS) and Costello syndrome (CS), two RASopathies caused by mutations in the downstream and upstream elements of the RAS pathway, respectively. Methods Sixteen individuals with CFCS and 23 individuals with CS were enrolled. Mutation data were recorded. Scalp hair, eyebrows and eyelashes of individuals with CFCS or CS were examined for texture, colour, density and morphology. Scalp hairs were examined by light microscopy. Results While both syndromes displayed abnormal hair, striking differences were observed, including darker and thicker scalp hair and sparse eyebrows and eyelashes in CFCS. By contrast, synophrys, trichomegaly and abnormalities of the scalp hair shafts were observed in CS. Possible correlation with straight hair and genotype was observed in CS. Conclusion The results emphasize the role of the RAS pathway in hair growth, improve accuracy of clinical diagnosis of CFCS and CS and provide a foundation for identification of therapeutic targets.

Eyelash trichomegaly: a systematic review of acquired and congenital aetiologies of lengthened lashes

“…In addition, eyelash trichomegaly was noted in a female infant with tetralogy of Fallot 150 . Similarly, a case series identified eyelash trichomegaly in 36% of patients with Costello syndrome, which is associated with hypertrophic cardiomyopathy 151 . Other reports of Costello syndrome note extremely long lashes requiring trimming in children as young as three years old 152 .…”

“…Of note, minoxidil, an agonist of the ABCC9 related potassium channel commonly used to stimulate scalp hair growth, may produce a similar phenotype 121 . Though this offers insight into potential mechanisms behind eyelash growth, high quality evidence supporting a direct link between eyelash trichomegaly and congenital heart disease is currently lacking 151,155 …”

The seventh international RASopathies symposium: Pathways to a cure—expanding knowledge, enhancing research, and therapeutic discovery

“…However, there are also clear differences. For instance, absent or sparse eyebrows, darker and thicker scalp hair, and keratin‐clogged hair follicles and sweat ducts are typically only observed in CFCS (Urban et al, 2020). Conversely, papillomas on the nose and face and deep acral creases are more typical in CS.…”

Current controversies in trichology: a European expert consensus statement

“…Forty-six experts from 10 different countries were invited to participate as panellists in the modified Delphi questionnaire; 45 of them participated in both rounds. Their nationalities included Spain (31) Portugal (3), Bulgaria (2), Poland (2), Russia (2), Belgium (1), India (1), Nigeria (1), Ukraine (1) and Georgia (1). They were selected given their expertise and interest in trichology.…”

“…Hair disorders, especially hair loss, are one of the most common conditions within dermatology practice that can significantly affect the patient’s quality of life 1 . In recent years, new diagnostic tools and therapeutic options have been suggested, but whether they are effective and safe to treat hair disorders still remains controversial in some cases, as available evidence is limited.…”