Congenital anonychia can occur either as an isolated abnormality or as part of the following syndromes: nail–patella syndrome, ankyloblepharon, ectodermal defects, cleft lip/palate (AEC), and ectrodactyly–ectodermal dysplasia clefting syndrome. The occurrence of brachydactyly with congenital anonychia/hypoplasia can also be a part of well-known syndromes such as aplasia cutis congenita; Cooks syndrome; Robinow syndrome; Coffin–Siris syndrome; Zimmermann–Laband syndrome; and deafness, onycho-osteodystrophy, and mental retardation syndrome.
A 2-year, 9-month-old girl child born out of a nonconsanguineous marriage came with the complaints of the absence of few nails involving both the hands and feet since birth with fever and pain when passing urine for 1 week. Her antenatal history was significant only for high maternal age. The child has been immunized for age and has no history of delayed milestones. No similar complaint was present in any other family members. There was no history of abnormality in gait or stature or any hearing impairment and difficulty in speech.
General physical examination and anthropometric evaluation were normal.
Cutaneous examination revealed the absence of the nails and shortening of digits involving the right middle and ring fingers along with the left middle, ring, and little fingers [Figure 1a.] The toe nails were also absent affecting the right great and 3rd toe and the left great toe and 2nd and 4th toes when shortening of only the left 4th toe [Figure 1b].
Oral examination showed heart-shaped tongue and deviation to the right side [Figure 2]. No abnormal dentition, hearing impairment, facial deformity, and ocular or skeletal abnormality was seen.
The ultrasonography (USG) of the knees showed the presence of both patellas (unossified). The radiographs of the hands showed the absence of the distal phalanx of the right middle and ring fingers including the left middle, ring fingers, and the left 4th toe including hypoplastic distal phalanx of the left great toe [Figure 3]. Magnetic resonance imaging (MRI) of the brain revealed no abnormality. X-ray of the kidney, urethra, and bladder (KUB) showed staghorn calculi in the left kidney. USG KUB revealed no congenital abnormality. Urine examination was suggestive of urinary tract infection and culture was positive for Klebsiella pneumoniae and Enterococci. Urine metabolic workup and serum parathyroid hormone level were normal.
Anonychia can be acquired or congenital. Acquired causes of anonychia include trauma, psoriasis, severe lichen planus, epidermolysis bullosa, and Stevens–Johnson syndrome and can potentially reverse with the treatment of the underlying pathology. Congenital anonychia can occur either as an isolated entity or as a part of other well-defined syndromes. Syndromic congenital anonychia is inherited as an autosomal dominant and is characterized by the presence of other malformations such as neurological, skeletal, or ectodermal dysplasias. On the other hand, nonsyndromic congenital anonychia (simple anonychia) exists as an isolated abnormality of the nail plate with either an autosomal dominant/recessive inheritance or can occur as sporadic phenomena. The autosomal recessive inheritance is linked to mutation in the R-spondin-4 gene (RSPO4) on chromosome 20p13. RSPO4 is a member of the R-spondin family of secreted proteins that play a major role in activating the Wnt/beta-catenin signaling pathway which also play a role for bone-dependent nail formation.
Exposure to certain drugs such as carbamazepine, phenytoin, warfarin, morphine, and trimethadione taken by the mother during the first and second trimesters of pregnancy can lead to congenital absence of nails.
Brachydactyly can either exist as an isolated phenomena or in association with other syndromes. Anonychia and hyponychia are closely associated with underlying bone deformities and proper distal and/or middle phalanx is mandatory for nail development. One of the most commonly used classifications for isolated form of brachydactyly provided by Bell and further elaborated by Temtamy et al. includes 11 distinct types (Type A1-A5, Type B, C, D E brachydactyly, Sugarman brachydactyly and Kirner deformity). However, syndromic forms have been associated with the different types of brachydactyly as seen in following syndromes: Albright hereditary osteodystrophy syndrome, Feingold syndrome (oculo-digito-esophageal-duodenal syndrome), Robinow syndrome, Rubinstein–Taybi syndrome, and Turner syndrome.
The association of congenital anonychia with brachydactyly without any other malformation, although a rare occurrence, has been frequently reported in the literature most commonly as classical Cook’s syndrome or with some clinical heterogeneity of the disease. In 1985, Cooks et al. reported the association of congenital anonychia/hyponychia in a kindred with a consistent finding of absent distal phalanges in the 5th fingers of both hands with concomitant hypoplasia of distal phalanges in the second to the fourth digits, and either digitilization and/or bulbous thumb. In addition, they also reported hypoplasia and absent distal phalanges in the toes. Subsequently, in 1986, Kumar and Levick also described a family with nail dysplasia and/or absent nails and long and broad finger-like thumbs with hypoplastic distal phalanges similar to Cook et al. However, absent or hypoplastic metacarpals as distinctive features along with the above changes were identified in this group of family members. In addition, the thumbs may show flattening, splitting, or duplication of the distal phalanges and there may be shortening of metacarpals and/or metatarsals, of which both features were absent in our case. Transmission of this type of brachydactyly is autosomal dominant. It is caused by mutations in the ROR2 gene located on chromosome 9 on 9q22.
Besides the association of anonychia with type B brachydactyly, our patient also had neurological manifestations of a heart-shaped tongue with atrophy and deviation of the tongue to the right side, for which a neurological assessment was made and unilateral congenital hypoglossal nerve palsy was considered after MRI brain ruled out the presence of any secondary cause of the nerve palsy. Unilateral congenital hypoglossal nerve palsy is extremely rare and its association with brachydactyly and anonychia has never been described before. The other neurological associations reported with anonychia are choreoathetosis and epilepsy, which are absent in our case.
Another unique association in our patient was the presence of a renal calculi. Staghorn calculi in a child can either be attributed to congenital anomalies of the kidney and urinary tract anatomy, metabolic diseases such as cystinuria, and alterations such as hypercalciuria and hyperuricosuria. Urinary tract infection can predispose to stone formation in toddlers, where fecal organisms of low virulence such as Escherichia coli and enterococci are known to form the periurethral flora. Stone resulting from infection can mold easily into the renal calyces to form staghorn calculi. In our case, ultrasonogram revealed no obvious renal anomalies and the metabolic workup was also negative.
The association of renal calculus with proteinuria and anonychia has been described in nail–patella syndrome. However, our case had shown the presence of unossified patellae in USG and also the brachydactyly present in our patient is not a feature of nail–patella syndrome.
Table 1 describes the various differential diagnoses of syndromic congenital anonychia and congenital brachydactyly with anonychia versus the findings in our patient.
Our patient had unique features of congenital brachydactyly with other congenital anomalies, thereby raising a possibility of syndromic forms of brachydactyly with anonychia. However, even after extensive review of literature, we could not classify her into any known syndromes. Genetic testing would have enabled us to determine the basis of her condition, but it could not be done due to limited resources. This case is interesting as it teaches us that there may be more unidentified syndromes that can be considered in the future. Moreover, a thorough neurological examination and X-ray for the detection of renal stones may be essential besides the skeletal survey.
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The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s) of the patient. In the form the parent(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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