case_images: PMC11288940_01
case_images: Phenotypic characteristics of the proband P. (A) Hyperkeratotic nodule on the skin of right shin. (B) Skin area with growth of an exophytic mass, epidermis with marked hyperkeratosis, verrucous papillomatosis and acanthosis, linear lichenoid lymphocytic infiltration (hematoxylin and eosin), x80. (C) Invasive complexes of neoplastic epithelium in the dermis, with dense lymphocytic infiltration, x200. (D) Concentric aggregations of the neoplastic epithelium with central keratinization, impaired maturation, moderate cytologic atypia, x350. (E) Surrent state of the area of operation. (F) Dermatoscopy reveals Wickham streae (left) and pseudo follicular openings surrounded by violaceous halo (right), typical for hypertrophic lichen ruber planus. (G,H) First days of life. (G) Erythematous rush. (H) Vesicles and erosions on the patient skin. (I-K) Present state. (I) Overview. (J,K) Areas of hyperpigmentation involving inner leg and armpit. (L) Homogenous brown pigmentation is visible under dermoscopy (Dermlite 4, polarized mode). (M) Confocal microscopy reveals uneven melanin accumalation in hyperpigmented spots. (N) Parietal hair thinning, brownish discoloration of the scalp in previously affected areas. (O) Areas of scarring alopecia, single hairs predominate (Dermlite x 10, polarized mode). (P) Dental malformations.
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case_images: PMC11288940_01_fmed-11-1402577-g001.jpg
case_images: fig1
case_images: Histological examination revealed invasive well-differentiated keratinizing SCC (Figures 1A-D). In vivo confocal laser scanning microscopy confirmed lichen planus with partial disruption of the epidermis, dyskeratosis and hyperkeratosis, irregular acanthosis, inflammatory infiltration, hypergranulosis, dilated vessels, and fibrosis (Figures 1E,F). Detailed phenotypic characteristics of P are presented on Figures 1G-P.
case_images: PMC11288940_02
case_images: Phenotypic characteristics of the proband's mother M (A-F) and sister S1 (G-J). (A-C) Areas of irregular pigmentation in M. (D) Parietal zone with hair thinning. (E) Dental malocclusion (adentia of both upper lateral insicors and also two molars on the lower jaw are missing). (F) Orthopantomogram shows anomalies in the positioning of individual teeth, adentia of both maxillary lateral insicors and two molars on the lower jaw. (G,H) Areas of hyperpigmentation on the trunk and legs in S1. (I) Parietal zone with sparse hair growth. (J) Mild dental malformations.
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case_images: fig2
case_images: At present, the parietal zone with sparse hair growth and mild dental malformations were observed (Figures 2G-J).
case_images: PMC11288940_03
case_images: Phenotypic characteristics of the proband's mother M (A-F) and sister S1 (G-J). (A-C) Areas of irregular pigmentation in M. (D) Parietal zone with hair thinning. (E) Dental malocclusion (adentia of both upper lateral insicors and also two molars on the lower jaw are missing). (F) Orthopantomogram shows anomalies in the positioning of individual teeth, adentia of both maxillary lateral insicors and two molars on the lower jaw. (G,H) Areas of hyperpigmentation on the trunk and legs in S1. (I) Parietal zone with sparse hair growth. (J) Mild dental malformations.
case_images: fmed-11-1402577-g002.jpg
case_images: PMC11288940_03_fmed-11-1402577-g002.jpg
case_images: fig2
case_images: At present, the parietal zone with sparse hair growth and mild dental malformations were observed (Figures 2G-J).
case_images: PMC11288940_04
case_images: Phenotypic characteristics of proband's sister S2 (A-G) and trichoscopic hair evaluation of family members (H-K). (A) Overall view. (B) Light brown linear, curved and "star-like" macules are preserved on the trunk. (C) Severe alopecia in parietal zone. (D) Compensatory tilt of the head to the left, corners of the mouth downwards, lips are not closed in the resting position. (E) Laying of the tongue between the teeth on the right side in the area of missing teeth. (F) The smile is asymmetrical, the tongue is inserted between the teeth on the right side. (G) Orthopantomogram reveals multiple tooth adentia. (H) Trichoscopy of the scalp of S1 and S2 demonstrates growth of mostly single hair, white peripilar dots (blue arrows), honeycomb-shaped pigmentation (green oval), and scalp discoloration (red arrows). (I) Keratinous perifollicular desquamation (purple arrow). (J) Boomerang-type hair bending in the proximal zone of growing single hair (shown by arrows). (K) A large number of single growing hair (brown arrows) and the presence of vellus hair (black arrows) on the scalp of M.
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case_images: PMC11288940_04_fmed-11-1402577-g003.jpg
case_images: fig3
case_images: Orthopantomogram reveled the absence of several deciduous teeth (lactodentia; Figures 3A-G). Discoloration, honeycomb pigmentation, and single hair growth were characteristic for all females; M had an increased number of vellus hairs on the vertex, indicating miniaturization of hair follicles, possibly due to their own sensitivity to androgens (Figures 3H-K).
case_images: Molecular-genetic analysis. (A) Long-range PCR with IKBKG primer pair In2/JF3R revealed IP-specific 2.6-kb band in patient samples (M - mother, P - proband, S1 - sister 1, S2 -sister 2) and the absence of PCR-product in healthy people (F - father of the family and (-) - negative control). (B) In contrast, bands amplified with primers specific for IKBKGP (JF3R/Rev2) showed no appreciable specificity between patients and controls. (C) Fragment analysis of PCR products amplified from undigested HPAII (-) and digested HPA (+) DNA of F, M and S2. In the F DNA, one major peak decreases significantly after HpaII digestion. In the undigested M DNA, the two major peaks represent two alleles with different numbers of short tandem repeats at the AR locus, after digestion the short allele is practically disappeared (red arrow). The S2 DNA displays the preferential loss of the active father's (F) allele (red arrow), while the inactivated M allele is preserved.
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case_images: PMC11288940_04_fmed-11-1402577-g004.jpg
case_images: fig4
case_images: The deletion of exon 4-10 of IKBKG gene was present in mother and three daughters, while absent in father and healthy control (Figures 4A,B). AR gene was investigated in the affected females using a HUMARA assay. All females had unbalanced inactivation of the X chromosome (> 90%) in peripheral blood leukocytes with the following values: P and M had 98%, S1 had 96%, and S2 had 99% of skewing (Figure 4C).