Anonychia Congenita - Rare Inheritance of a Rare Disorder.

Non syndromic Anonychia congenita or congenital absence of finger and toe nails is a rare disorder known to occur due to autosomal recessive inheritance of mutation in the R-spondin-4 gene. We present a case of a 32 year old female born of a non-consanguineous marriage presenting with complete absence of finger and toe nails since birth and similar presentation in family members over four generations, suggesting an autosomal dominant inheritance.

Zimmermann-Laband syndrome in monozygotic twins with a mild neurobehavioral phenotype lacking gingival overgrowth-A case report of a novel KCNN3 gene variant.

Zimmermann-Laband syndrome is a rare, heterogeneous disorder characterized by gingival hypertrophy or fibromatosis, aplastic/hypoplastic nails, hypoplasia of the distal phalanges, hypertrichosis, various degrees of intellectual disability, and distinctive facial features. Three genes are considered causative for ZLS: KCNH1, KCNN3, and ATP6V1B2. We report on a pair of female concordant monozygotic twins, both carrying a novel pathogenic variant in the KCNN3 gene, identified using exome sequencing. Only six ZLS patients with the KCNN3 pathogenic variant have been reported so far. The twins show facial dysmorphism, hypoplastic distal phalanges, aplasia or hypoplasia of nails, and hypertrichosis. During infancy, they showed mild developmental delays, mainly speech. They successfully completed secondary school education and are socio-economically independent. Gingival overgrowth is absent in both individuals. Our patients exhibited an unusually mild phenotype compared to published cases, which is an important diagnostic finding for proper genetic counseling for Zimmermann-Laband syndrome patients and their families.

Further phenotypic features and two novel POC1A variants in a patient with SOFT syndrome: A case report.

Short stature, onychodysplasia, facial dysmorphism and hypotrichosis (SOFT) syndrome is a rare autosomal recessive disease caused by POC1 centriolar protein A (POC1A) pathogenic variants. However, knowledge of genotypic and phenotypic features of SOFT syndrome remain limited as few families have been examined; therefore, the clinical identification of SOFT syndrome remains a challenge. The aim of the present case report was to investigate the genetic cause of this syndrome in a patient with a short stature, unusual facial appearance, skeletal dysplasia and sparse body hair. Giemsa banding and exome sequencing were performed to investigate the genetic background of the family. Spiral computed tomography and magnetic resonance imaging were used for investigating further phenotypic features of the patient. Exome sequencing identified that POC1A had two compound heterozygous variants, namely c.850_851insG and c.593_605delGTGGGACGTGCAT, which, to the best of our knowledge, have not been reported elsewhere. Novel phenotypes were also identified as follows: i) Metaphyseal dysplasia was alleviated (and/or even disappeared) with age; ii) the density of the femoral neck was uneven and the hyperintensity signal of the metaphysis was stripe­like. Thus, the present case report expands the knowledge regarding phenotypic and genotypic features of SOFT syndrome.

A 17q24.3 duplication identified in a large Chinese family with brachydactyly-anonychia.

BACKGROUND: Brachydactyly (BD) is a rare autosomal dominant inherited disease characterized by shortness of the fingers and/or toes, which has been classified into the subtypes A-E. However, the exact cause and mechanism of BD remain to be illuminated. Here, we aim to reveal the clinical and genetic characteristics of a subtype of BD, brachydactyly-anonychia. METHODS: In this study, a large Chinese family with three members affected by brachydactyly-anonychia was investigated. Both whole-exome sequencing and microarray-based comparative genomic hybridization (CGH) were performed on this family and the results of copy number variation (CNV) were verified by quantitative real-time PCR (qPCR). RESULTS: All the affected individuals showed short fingers and toes as well as missing nails; and the absence of middle phalanges in figure II-V of the upper and lower extremities was observed by X-ray examination. A duplication involving in the region of 17q24.3 was detected by CGH. The results of qPCR also represented this duplication in 17q24.3 in all the patients. CONCLUSION: In summary, our findings suggest that 17q24.3 duplication is the genetic cause of brachydactyly-anonychia in this family, which support the prior report that brachydactyly-anonychia is associated with 17q24.3 duplication, and further indicates the pathogenic correlation between BD and CNVs.

Anonychia congenita in different generations of a single Saudi family.

Anonychia refers to the absence of nail plates owing to an autosomal dominant or recessive inheritance. Congenital anonychia is a rare condition that may be associated with other ectodermal or mesodermal malformations like epidermolysis bullosa, (deafness, onychodystrophy, osteodystrophy, and mental retardation) syndrome and Iso-Kikuchi syndrome. Here, we report 3 cases with anonychia congenita appearing in different generations of a single family in Kingdom of Saudi Arabia.

Onychodystrophy as the only sign of congenital candidiasis.

Congenital candidiasis infection often presents as a skin rash with variable involvement of nails and mucous membranes. Isolated nail involvement is rare, may present late, and can often be managed with topical antifungal medication. We report a case of congenital candidiasis limited to the fingernails that resolved completely within 3 months with topical treatment.

Distal Dorsal Dimelia: A Disturbance of Dorsal-Ventral Digit Development.

PURPOSE: Congenital palmar nail (distal dorsal dimelia [dDD]) of the hand is a rare malformation most commonly affecting the little finger. The purpose of this report was to review the features and associations of this rare disorder and discuss the suspected underlying etiology in light of our current understanding of developmental biology. METHODS: In this retrospective cohort study from 3 practices, we describe our collective experience and review the reported literature on this disorder both as an isolated condition and in conjunction with other anomalies. RESULTS: We examined 15 fingers with dDD, 5 of which involved little fingers. We also found dDD in 6 cases with radial polydactyly (preaxial polydactyl type II [PPD2]) and in 1 case of cleft hand involving digits adjacent to the clefted web space (the index and middle fingers). Cases of little finger dDD were also associated with prominent clefting of the adjacent web space in 4 of 5 cases. All cases had stiffness of the interphalangeal joints and loss of palmar creases consistent with dorsalization of the palmar aspect of the digit. When combined with 63 fingers reported in the literature with dDD, 3 patterns were evident. The most common form occurred in little fingers (n = 50; 64%; dDDu). The next most common form was reported in association with cleft hands (n = 16; 21%; dDDc). Radial digits in association with either radial polydactyly (PPD2) or radial longitudinal deficiency were also susceptible to dDD (n = 12; 15%; dDDr). CONCLUSIONS: Congenital dDD is a disturbance of terminal dorsal-ventral digit patterning. The distribution of this condition with little fingers, clefting, and altered radial digit formation (PPD2 or radial longitudinal deficiency), as well as recent genetic and animal studies, suggests that dDD and altered dorsal-ventral patterning are linked to abnormal apical ectodermal ridge boundary formation. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

Progressive reticulate skin pigmentation and anonychia in a patient with bone marrow failure.

KEY TEACHING POINTS.

A novel mutation in the RSPO4 gene in a patient with autosomal recessive anonychia.

The Wnt signalling pathway is a major pathway involved in the embryogenic development of the various organs of the body. Appropriate signalling in this pathway relies on the proper functioning of several proteins including the R-spondin family of proteins. Deactivating mutations in R-spondin 4 are associated with anonychia. We present the case of a 26-year-old man presenting with anonychia of the 20 nails, which had been present since birth. Using genetic studies, we identified a novel nonsense mutation, c.164-165TC>AA, characterized by two consecutive mismatch bases. To our knowledge, this mutation is the first to be reported in R-spondin 4 in a Lebanese population. Evaluating new patients with anonychia provides fruitful clinical and molecular findings.