Nail-patella syndrome (NPS) is an uncommon autosomal dominant condition marked by nail dysplasia, skeletal abnormalities, and variable renal manifestations, resulting from mutations in the LMX1B gene. We report a rare case of a 23-year-old male presenting with nephrotic-range proteinuria, characteristic skeletal manifestations of NPS, and a family history of renal failure. Genetic testing identified a previously unreported heterozygous missense variant in the homeodomain of LMX1B (c.791A>C; p.Gln264Pro), supporting its pathogenicity. The absence of patellar hypoplasia in our patient highlights the phenotypic variability of NPS. This case reinforces the importance of detailed physical examination and targeted genetic testing in diagnosing nephrotic syndromes.

Congenital hyponychia and anonychia are extremely rare nail disorders characterized by the partial or complete absence of nails. These conditions may be inherited or associated with in utero exposure to teratogenic substances. A full-term male neonate underwent routine head-to-toe examination in the labor room. The baby was noted to have both incomplete (hyponychia) and complete (anonychia) absence of fingernails and toenails. No other systemic abnormalities were identified. Isolated congenital hyponychia and anonychia are uncommon findings in neonates. In the absence of syndromic features, the condition generally carries an excellent prognosis.

Autoimmune polyendocrinopathy syndrome type 1 (APS-1) is a rare autosomal recessive disorder caused by pathogenic variants in the AIRE gene and classically characterized by the triad of hypoparathyroidism, chronic mucocutaneous candidiasis, and adrenal insufficiency. Although hypoparathyroidism is often the earliest manifestation, isolated and prolonged monosymptomatic presentations remain uncommon and may delay recognition of the syndrome. We report the case of a child who was first presented at four years of age with severe hypocalcemia in the setting of acute gastroenteritis and was diagnosed with hypoparathyroidism. Apart from hypomagnesemia and hyperphosphatemia, extensive workup revealed no additional autoimmune or endocrine abnormalities. Genetic testing subsequently identified a homozygous likely pathogenic stop-loss AIRE gene mutation, confirming APS-1. Over a three-year follow-up period, the patient remained clinically stable with well-controlled hypoparathyroidism, except for hypocalcemic episodes during diarrheal illnesses, and persistently normal adrenal, thyroid, pancreatic, and celiac screening. The first additional disease feature emerged three years after the initial presentation, at the age of seven years, when a fungal nail infection consistent with mucocutaneous candidiasis was noted. This case highlights the marked phenotypic variability with delayed evolution of APS-1 and underscores that isolated hypoparathyroidism, even when severe, may precede other disease components by several years. Early genetic testing in children with apparently isolated hypoparathyroidism allows anticipatory guidance, structured surveillance, and timely recognition of evolving autoimmune manifestations.

A 15-year-old girl presented with isolated anterolateral tibial bowing without fracture, an unusual manifestation. The deformity was initially corrected with a double-level osteotomy sparing the apex and intramedullary nail fixation. A second corrective procedure was performed for residual deformity, resulting in satisfactory alignment and union. Congenital tibial pseudarthrosis most often progresses to fracture in early childhood, but this rare presentation without fracture highlights the variability of the condition. Successful correction was achieved through staged, apex-preserving, double-level osteotomies and intramedullary fixation, providing a potential strategy for atypical cases.

Ectodermal dysplasias are clinically and genetically heterogeneous congenital disorders characterized by abnormal development of at least two of the four ectodermal tissues: teeth, hair, nails, and sweat glands. In this study, we summarized the clinical and molecular characteristics of the patients and contributed to the genotype-phenotype correlation. For genetic diagnosis, single-gene testing, clinical exome sequencing, whole-exome sequencing, and variant confirmation analyses were performed. In this study, 30 ectodermal dysplasia patients from 18 families and six patients with isolated ectodermal anomalies from three families were analyzed. A total of 21 unique variants were identified, five of which were novel. Of these, seven were classified as pathogenic, 11 as likely pathogenic, and three as variants of uncertain significance (LIPH, TSPEAR, HR). Hypohidrotic ectodermal dysplasia was the most frequently identified subtype, with variants in the EDAR gene found in 10 patients and in the EDA gene in seven patients. Two patients harbored WNT10A variants. Variants in the CDH3 gene were identified in six patients with macular degeneration. Additionally, variants in the LIPH and LPAR6 genes were detected in three patients presenting with woolly hair. In the remaining eight patients, variants were identified in the HR, TSPEAR, TP63, DSG1, and CST6 genes. Microcephaly was observed in 47% (8/17) of patients in the hypohidrotic ectodermal dysplasia group (EDA, EDAR) and in 66% (4/6) of patients carrying CDH3 variants. The patient with a TSPEAR variant also had Beckwith-Wiedemann syndrome. Our clinical findings, together with the identification of novel variants in EDAR, LIPH, LPAR6, HR, and TP63, expand the clinical and molecular spectrum of ectodermal dysplasias. A potential association between microcephaly and ectodermal dysplasia is discussed. This study highlights the genetic heterogeneity of ectodermal dysplasias and emphasizes the importance of combining detailed clinical evaluation with molecular diagnostics. • Ectodermal dysplasias (EDs) are congenital disorders characterized by abnormal development of at least two of four ectodermal structures, such as hair, nails, teeth, and sweat glands. EDs represent a clinically and genetically heterogeneous group of disorders with over 200 distinct types described. • In the current study, we report the clinical and molecular genetic analysis of 36 patients and contribute to the genotype-phenotype correlation. Five novel variants were identified. Microcephaly was observed in 47% of patients in the hypohidrotic ectodermal dysplasia group and in 66% of patients carrying CDH3 variants. The patient with a TSPEAR variant also had Beckwith-Wiedemann syndrome.