¹Department of Dermatology, Faculty of Medicine and Medical Sciences, Sana’a University, Yemen
²Department of Conservative Dentistry, Faculty of Dentistry, Sana’a University, Yemen

*Address for Correspondence:Mohammad Ali Alshami, Department of Dermatology, Faculty of Medicine and Medical Sciences, Sana’a University, Sana’a 1064, Yemen. E-mail Id: Mohammadalshami62@gmail.com

Submission: 13 April, 2026 Accepted: 15 May, 2026 Published: 19 May, 2026

Copyright: © 2026 Alshami MA, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords:Skin; Hair; Nail; Ectodermal Dysplasia

Background: Pure hair–nail ectodermal dysplasia (PHNED) is a rare subtype of ectodermal dysplasia characterized by congenital hair and nail involvement, with teeth, sweating, and other ectodermal structures remaining unaffected when the disorder is fully phenotypically assessed. Only a limited number of PHNED cases have been reported, and the present father–son presentation adds to this rare clinical literature. PHNED has been associated with pathogenic variants in KRT74, KRT85, and HOXC13. Reported patients with HOXC13- associated PHNED often show severe hypotrichosis or complete alopecia with nail dystrophy; in the present family, the phenotype included congenital alopecia of the scalp, eyebrows, and eyelashes and dystrophy of all 20 nails.
Case presentation: A 27-year-old Yemeni man and his 7-monthold son presented with congenital total alopecia involving the scalp, eyebrows, and eyelashes, along with dystrophy of all 20 nails. Genetic testing identified an HOXC13 variant in the father; the son was clinically affected but was not genetically tested.
Conclusion: This father–son presentation is clinically consistent with PHNED and, in the genetically tested father, supports the association between HOXC13 variants and PHNED; it adds to the limited literature on HOXC13-associated hair–nail ectodermal dysplasia.

ED: Ectodermal dysplasia; HOXC13: homeobox C13 gene; HOXC13: homeobox C13 protein; KRTHB5: Keratin, hair, basic, 5 (hair matrix and cuticle keratin gene); KRT74: keratin 74 gene; KRT74: keratin 74 protein; KRT85: keratin 85 gene; KRT85: keratin 85 protein; PHNED: Pure hair-nail ectodermal dysplasia

Pure hair–nail ectodermal dysplasia (PHNED) is an extremely rare subtype of ectodermal dysplasia (ED) limited to the hair and nails, while other ectodermal structures, such as the teeth and sweat glands, remain unaffected. The first case of ED was described by Thurnam in 1848, and the term “ectodermal dysplasia” was later coined by Weech in 1929 [1,2]. PHNED was first described by Hofmann in 1908 and subsequently defined by Pinheiro in 1992; since then, only approximately 70 cases of PHNED have been reported worldwide.
Compared with some reported KRT74- or KRT85-associated phenotypes, HOXC13-associated PHNED has frequently been described with severe hypotrichosis or complete alopecia. Nail dystrophy in PHNED may involve all digits and can present with irregular, fragile, or dystrophic nails; in the present father, all 20 nails were affected and showed distal dystrophy with marked downward curvature.

A 27-year-old Yemeni man presented with congenital total alopecia affecting the scalp, eyebrows, and eyelashes, accompanied by dystrophy of all 20 nails [Figure 1]. On close examination, sparse short black hairs were visible within some scalp follicles despite clinically apparent total scalp alopecia [Figure 2]. All 20 nails were distally dystrophic, with marked downward curvature [Figure 3]. The patient had normal dentition and reported normal sweating. Scalp biopsy from the father showed marked follicular hypoplasia, with a substantially reduced number of structurally disorganized hair follicles. The patient was otherwise healthy, with no associated systemic abnormalities. The presence of similarly affected siblings with reportedly unaffected parents raises the possibility of autosomal recessive inheritance in the father’s sibship. Although the affected father and son suggest vertical transmission, the unaffected parents and affected siblings of the father also raise the possibility of autosomal recessive inheritance; definitive assessment of inheritance would require segregation analysis, including testing of the son and relevant relatives. [Figure 4].

The patient’s 7-month-old son showed congenital alopecia of the scalp, eyebrows, and eyelashes and dystrophy of all 20 nails, closely resembling the father’s phenotype; genetic testing was not performed [Figure 5].

EDs are a rare group of genodermatoses that affect tissues derived from the ectoderm, including the hair, nails, teeth, and sweat glands. The first classification system for EDs was proposed by Freire-Maia and Pinheiro in 1982 and was subsequently updated in 1994 and 2001, when PHNED was included [3,4]. PHNED is a rare subtype of ED with genetic heterogeneity and reported autosomal recessive and autosomal dominant inheritance patterns [5,6]. A summary of the clinical and genetic features of previously reported cases is provided in [Table 1]. Congenital absence or marked reduction of scalp, eyebrow, and eyelash hair can overlap clinically with other genodermatoses, including atrichia with papular lesions; however, the combination of congenital alopecia with generalized nail dystrophy favors

PHNED in the present family. Hypohidrotic ectodermal dysplasia may present with hypotrichosis, but it is usually distinguished by abnormal sweating and dental anomalies, features not documented in the father in the present report. Alopecia totalis or universalis may rarely occur early in life and can be associated with nail changes, but the congenital onset, familial pattern, and generalized dystrophy of all nails in this family are more consistent with PHNED. In the present father, all fingernails and toenails were distally dystrophic with marked downward curvature.. Congenital hyponychia or micronychia may also be considered, but these conditions primarily involve nail hypoplasia and do not usually account for the combined congenital alopecia and generalized onychodystrophy seen in this family. Our literature review identified a limited number of reported PHNED cases, including two Yemeni siblings previously reported by the first author (Table 1). Pathogenic variants in KRT85, HOXC13, and KRT74 have been reported in patients with PHNED or closely related hair–nail phenotypes [7,8]. KRT85 and KRT74 encode type II keratins, whereas HOXC13 encodes a transcription factor involved in regulating keratin and keratin-associated protein genes. Keratins are major intermediate filaments within hair and nail keratinocytes, where they maintain structural integrity and confer mechanical resilience. They are classified into two types: type I keratins, encoded by genes on chromosome 17, and type II keratins, encoded by genes on chromosome 12.

The clinical features observed in the present father and son resemble those in the previously reported Yemeni siblings and in the phenotype described by Naeem et al., who reported a pathogenic variant in the hair keratin gene now referred to as KRT85 [8,9]. The histopathologic findings of the scalp biopsy were similar to those reported by Lin et al. [7]. Genetic testing of the son was not performed because of financial constraints.

The father and son showed clinical features consistent with previously reported PHNED cases, and the father’s scalp histopathology was comparable to findings described in earlier HOXC13-associated PHNED reports. To the best of our knowledge, the father represents the first genetically confirmed case of PHNED reported from Yemen, while the son represents a clinically affected familial case without molecular confirmation.

Permission was obtained from the patients to publish their data in the study.

Alshami MA, Alshami AM, Alshami HM, Lutf RM. Familial Pure Hair–Nail Ectodermal Dysplasia in Yemen: A Father–Son Case Report with Clinical Correlation. J Clin Investigat Dermatol. 2026;14(1): 1