Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2025;15(3):5285 1 Clinical and Trichoscopy Features in Trichorhinophalangeal Syndrome: A Multicenter Retrospective Study Daniel Fernandes Melo1, Rita Fernanda Cortez de Almeida1, Carla Jorge Machado2, Marcela Benez1, Pedro da Rocha Andrade Neto1, André Luiz Vairo Donda1, Isabela Peron Melhado3, Rogerio Nabor Kondo3, Sidney Frattini4, Giselle Pinto5, Aline Donati6 1 Department of Dermatology, Rio de Janeiro State University, Rio de Janeiro, Brazil 2 Preventive and Social Medicine Department, Federal University of Minas Gerais, Belo Horizonte, Brazil 3 Department of Dermatology, Londrina State University, Londrina, Brazil 4 General Surgery, Grand River Hospital and Saint Mary’s General Hospital, Both Kitchener-Waterloo, Ontario, Canada 5 Dermatology, Private Practice, Porto Alegre, Brazil 6 Department of Dermatology, Municipal Public Servant Hospital (HSPM), São Paulo, Brazil Key words: Trichorhinophalangeal Syndrome, Trichoscopy, Hair Disorders, Clinical Features Citation: Melo DF, Cortez de Almeida RF, Machado CJ, et al. Clinical and Trichoscopy Features in Trichorhinophalangeal Syndrome: A Multicenter Retrospective Study. Dermatol Pract Concept. 2025;15(3):5285. DOI: https://doi.org/10.5826/dpc.1503a5285 Accepted: April 2, 2025; Published: July 2025 Copyright: ©2025 Melo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: André Luiz Vairo Donda, Boulevard 28 de setembro, 77, Vila Isabel, Rio de Janeiro, RJ, Brazil. CEP: 20.551-031. Orcid ID: 0000-0002-6735-5469. E-mail: alvd@live.com Introduction: Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disor- der characterized by trichological, craniofacial, and skeletal abnormalities. To date, limited data are available on hair involvement in TRPS, especially those focusing on trichoscopy. Objective: We aimed to describe the epidemiology and the clinical and trichoscopy features of TRPS. Methods: We performed a retrospective multicenter study using chart review and images from six patients with a confirmed diagnosis of TRPS. Hair density (hair/field; field 13×1.4 mm) was classified as high (>30), medium (21-30), low (11-20), very low (5-10), or hairless (<4). The distance between follicular units, ranging from 1.0 mm to 1.4 mm, was considered normal. Results: Most patients were females, with a median age of 12 at diagnosis. Hair density ranged from very low to medium. All female patients presented a high occipital hairline. Our patients had exclu- sively non-terminal hairs and no case with high hair density, following the literature, which describes thin and sparse hairs. Hair density was related to a higher proportion of single hair units, while the distance between follicles was within normal limits. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2025;15(3):5285 Introduction Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterized by trichological, cra- niofacial, endocrinological, and skeletal abnormalities [1,2]. It is classified into three types (I-III), each exhibiting vary- ing degrees of clinical features, including a prominent nose, craniofacial dysmorphism, and limb abnormalities such as brachydactyly. Genetic studies have identified mutations in the TRPS1 gene as a key contributor to the condition [1,2]. The management of TRPS requires a multidisciplinary ap- proach, focusing on symptomatic treatment and genetic counseling for affected individuals and their families [1,2,3]. Its trichological findings include thin, sparse, or brittle hair, severe hypotrichosis, or diffuse non-scarring alopecia [1,3]. To date, limited data are available on hair involvement in TRPS, especially those focusing on trichoscopy. Objective This multicenter retrospective study aimed to describe the epidemiology, clinical features, and trichoscopy of TRPS. Methods We performed a retrospective review of chart data and im- ages from four different specialized trichology centers. Six patients with a confirmed diagnosis of TRPS were enrolled. Figure 1 provides clinical and trichoscopy pictures of TRPS patients, demonstrating our main findings. Trichoscopy had Figure 1. (A) Clinical presentation of trichorhinophalangeal syndrome (TRPS) in a female patient showing low hair density, thin hairs, and high occipital hairline. (B) An example of a male patient with TRPS presenting with reduced frontal and vertex hair density. (C) Occipital view of the same male patient with normal hair density. (D) Trichoscopic image from the occipital scalp showing exclusively non-terminal hairs (<90 µm) and normal dis- tance between follicles (range 1.19–1.50 mm; ×20). (E) Manual trichoscopy from the frontal scalp of a male patient showing reduced hair shaft diameter and frontal-occipital inversion. (F) Manual trichoscopy of the occipital scalp of a male patient with normal hair diameter and frontal-occipital inversion. Conclusion: TRPS is notably uncommon, with hair alterations being important for diagnosis, where trichoscopy serves as a valuable tool. Our study found a normal hair diameter relationship (frontal ≥ occipital) in females, while the male patient exhibited frontal-occipital inversion. Low hair density may result from an increased number of single hair units rather than from follicular distance. The high occipital hairline is proposed as a diagnostic pearl, warranting further studies to validate our findings. Original Article | Dermatol Pract Concept. 2025;15(3):5285 3 been obtained with manual trichoscopy and Fotofinder and then grouped into scalp areas for analysis. Hair density (hair/field; field 13X1.4mm) was classified according to de Lacharrière et al., based on Fotofinder images, as high (>30), medium (21-30), low (11-20), very low (5-10), and hairless (<4) [4]. The distance between follicular units, ranging from 1.0 mm to 1.4 mm, was considered normal. [5] Results Most patients were females (n=5), with a median age of 12 at diagnosis (9–14 years old). All clinical and demographic data can be found in Table 1. All female patients presented a higher occipital hairline (Figure 1A). Under trichoscopy, hair density ranged from very low to medium. Single hair units Table 1. Clinical and Trichoscopy Findings in Six Patients With Trichorhinophalangeal Syndrome. Patients/Disease Characteristics Categories or Statistics Obtained Values Female Male Phototype I 0 II 1 III 3 IV 2 V/ VI 0 Hair type African or Asian 0 0 Caucasian 5 1 Body mass index categories Normal 3 1 Overweight 1 0 Obese 1 0 Other comorbidities No 5 1 Yes 0 0 Age at disease diagnosis Median (interquartile range) 12 (2) 12 (0) Minimum; Maximum 9; 14 12; 12 Type of trichorhinophalangeal syndrome 1 4 0 2 0 0 3 0 0 Unknown type 1 1 Family history of androgenetic alopecia No 0 0 Yes, paternal 4 1 Unknown family history 1 0 Slow growth speed No 0 0 Yes 5 1 Yellow dots (frontal scalp) ≤ 4 per field (20x magnification) 4 1 > 4 per field 1 0 Hair density (hair/field; field 13×1.4 mm) Frontal Hairless (<4) 0 0 Very low (5-10) 1 0 Low (11-20) 2 1 Medium (21-30) 2 0 High/Very high (>30) 0 0 Occipital Hairless (<4) 0 0 Very low (5-10) 1 0 Low (11-20) 2 0 Medium (21-30) 1 1 High/very high (>30) 0 0 Unknown hair density 1 0 Table1 continues 4 Original Article | Dermatol Pract Concept. 2025;15(3):5285 Patients/Disease Characteristics Categories or Statistics Obtained Values Female Male Frontal-occipital inversion No 4 0 Yes 0 1 Unknown 1 0 Single hair unit (>20%) Frontal No 1 0 Yes 4 1 Occipital No 1 1 Yes 3 0 Unknown single hair unit 1 0 Hair shaft diameter in categories Frontal Thin (30-40 µm) 1 1 Medium/Intermediate (50-80 µm) 4 0 Terminal (90 -110 µm) 0 0 Occipital Thin (30-40 µm) 3 0 Medium/Intermediate (50-80 µm) 1 1 Terminal (90 -110 µm) 0 0 Unknown hair shaft diameter 1 0 Distance between shafts (mm) Frontal Median (Interquartile Range) 1.27 (0.11) 1.19 (0.0) Minimum; Maximum 1.15; 1.40 1.19; 1.19 Occipital Median (Interquartile Range) 1.26 (0.14) 1.50 (0.0) Minimum; Maximum 1.19; 1.40 1.50; 1.50 Note: All three continuous variables were tested, and variables were considered to be normally distributed based on Shapiro-Wilk normality test (P>0.05). Table 1. Clinical and Trichoscopy Findings in Six Patients With Trichorhinophalangeal Syndrome. (continued) predominated, especially in the frontal scalp (five out of six patients). The mean distance between shafts was 1.25 mm (range 1.19–1.40) in the frontal scalp and 1.32 mm (range 1.19–1.50) in the occipital scalp. Hair shaft diameter analy- sis showed exclusively non-terminal hairs (<90 µm), regard- less of the scalp area (Figure 1D). The mean shaft diameter of the frontal scalp was greater than of the occipital in all but one male patient, who exhibited frontal-occipital inversion (Figures B, C, E, and F). Discussion The clinical findings associated with TRPS exhibit considerable variability; however, the three recognized types (I-III) share certain manifestations. Notable skeletal abnormalities include short stature, brachydactyly, and shortened phalanges or feet. Physical examination plays a crucial role in the diagnostic process, particularly as many of the abnormalities presented are dermatological in nature. Additionally, affected individu- als may exhibit facial dysmorphism, typically characterized by midline features. While hair and nail abnormalities are nonspe- cific, they have been documented in the literature [2]. An interesting finding that might be a clue to the clini- cal diagnosis of the syndrome in female TRPS patients is a higher occipital hairline, also observed by Seitz et al [1]. On trichoscopy, our patients had exclusively non-terminal hairs and no case with high hair density, following the literature, which describes thin and sparse hairs [2]. Lower thickness of hairs may be explained by the smaller duration of the an- agen phase of the hair cycle, which is the syndrome’s hall- mark [3]. The differential diagnosis should encompass other genetic disorders characterized by abnormalities of the hair, nose, and limbs. In terms of dermatological findings, condi- tions such as monilethrix, ectodermal dysplasia, early-onset androgenetic alopecia, and hypotrichosis must be consid- ered [6,7]. Based on our findings regarding hair density, we hypoth- esize that the lower hair density observed in TRPS patients is due to a higher proportion of single hair units rather than to a sparse distribution, since the distance between follicles remains within normal limits [5]. There was no increase in yellow dots in most cases. Future studies with scalp biopsy may confirm whether the low hair density derives from a decline in follicular density. Original Article | Dermatol Pract Concept. 2025;15(3):5285 5 characterization of 3 members of a family and 1 sporadic case. Arch Dermatol. 2001;137(11):1437-42. DOI: 10.1001/arch- derm.137.11.1437. PMID: 11708946. 2. Simonetti O, Radi G, Molinelli E, Diotallevi F, Offidani A. Trichorhi- nophalangeal syndrome: a case report and brief literature review. Acta Dermatovenerol Alp Pannonica Adriat. 2022;31(1):43-46. DOI: 10.15570/actaapa.2022.6. PMID: 35339132. 3. García-García SC, Herz-Ruelas ME, Gomez-Flores M, Vázquez-Herrera NE, Misciali C, Tosti A, Chavez-Alvarez S, Ocampo-Candiani J, Villarreal-Martinez A. Association of Trichorhinophalangeal Syndrome and Loose Anagen Syndrome: A Case Report. Skin Appendage Disord. 2020;6(3):162-167. DOI: 10.1159/000506524. PMID: 32656236. 4. de Lacharrière O, Deloche C, Misciali C, Piraccini BM, Vincenzi C, Bastien P, et al. Hair diameter diversity: a clinical sign reflecting the follicle miniaturization. Arch Dermatol. 2001; 137(5):641-6. PMID: 11346342. 5. Jimenez F, Ruifernández JM. Distribution of human hair in fol- licular units. A mathematical model for estimating the donor size in follicular unit transplantation. Dermatol Surg. 1999; 25(4):294-8. DOI: 10.1046/j.1524-4725.1999.08114.x. PMID: 10417585. 6. Piccolo V, Argenziano G. Monilethrix. JAMA Dermatol. 2024;160(12):1353-1354. DOI: 10.1001/jamadermatol.2024 .3892. PMID: 39441615. 7. Santos T.S., Frattini S.C.M., Fernandes de Almeida Pinto K., Llerena jr. J.C., Melo D.F. Early-onset androgenetic alopecia: a clue to the diagnosis of tricho-rhino-phalangeal syndrome. Eur. J. Pediat. Dermatol.  2016;26(2):75-8. DOI:10.26326/2281-9649 .26.2.1220. Limitations Limitations of this study include the small sample size, lack of standardization of videodermoscopy images, and the ab- sence of an age-matched control group. Conclusion Trichorhinophalangeal syndrome is notably uncommon, and hair alterations play an important role in its diagnosis, with trichoscopy identified as a helpful diagnostic tool. Our study revealed a normal hair diameter relationship (frontal ≥ occip- ital) in all female patients, while the male patient exhibited frontal-occipital inversion. We further emphasize that the ob- served low hair density in TRPS patients may be attributed to an increased number of single hair units rather than to the dis- tance between follicular units. Notably, the high occipital hair- line emerged as a diagnostic pearl that could assist clinicians in identifying this condition more effectively. This case series detailed the trichoscopic features of TRPS, including hair den- sity, thickness, and the distance between shafts, while high- lighting the need for further studies to confirm our findings. References 1. Seitz CS, Lüdecke HJ, Wagner N, Bröcker EB, Hamm H. Trichorhinophalangeal syndrome type I: clinical and molecular