Yunis-Varon syndrome (YVS; MIM: 216340) is a rare autosomal recessive lysosomal storage disorder caused by biallelic mutations in FIG4, characterized by skeletal, neurological, and ectodermal abnormalities. This systematic review analyzes 15 cases with biallelic FIG4 variants and a clinical diagnosis of YVS to refine the clinical phenotype and diagnostic criteria, as well as a further 25 clinical diagnoses without FIG4 variants. Three "hand and feet" criteria were developed, identifying 1: bilateral and symmetrical thumb aphalangia with or without first metacarpal aplasia or hypoplasia, 2: aphalangia of at least one other upper limb digit, and 3: hallux absence or proximal positioning consistent with aplastic or hypoplastic first metatarsal. These limb abnormalities serve as highly characteristic diagnostic features. We also show that a significant proportion of cases without molecular confirmation in the literature are likely to be misdiagnosed. All molecularly confirmed cases with published photographs or radiographs exhibited a characteristic "1-2 digital pattern" with the first digit being most severely affected, followed by the second digit, and the remaining digits being more mildly affected. Additional consistent features included microretrognathia, short philtrum with everted upper lip, sparse hair and brows, wide fontanelles, and variable brain abnormalities including ventriculomegaly and cortical malformations. Clavicular hypoplasia or aplasia was common, but less consistent a finding than the digital abnormalities described. Median age at last follow-up or death was 669 days. This review demonstrates that YVS has a highly characteristic and recognizable phenotype, with digital abnormalities representing the most diagnostically valuable finding warranting FIG4 sequencing.

Various surgical techniques have been utilized for thumb reconstruction in the setting of aphalangia. Given abnormal proximal anatomy, nonvascularized toe phalangeal transfer has been a popular surgical technique in a subset of patients with monodactylous symbrachydactyly. However, altering the appearance of a noninvolved foot is often unappealing to many parents. Here we detail a surgical technique of thumb reconstruction utilizing the index metacarpal as a nonvascularized graft to improve thumb length and stability. This technique avoids the donor site morbidity associated with toe phalangeal transfer and has demonstrated good results at short-term follow-up.

Congenital limb deformities are very rare conditions and the knowledge about etiology, pathogenesis, clinical presentation and treatment is still poor. Moreover, many defects are still not reported in veterinary literature. This report documents clinical and radiographic findings in three dogs with congenital deformity involving the distal extremities. Case 1 was affected with bilateral aphalangia of the pedes, case 2 presented a combination of brachydactyly and syndactyly, whereas in case 3 a unilateral ectrodactyly was observed. To the authors' knowledge, brachydactyly, as well as aphalangia, are very uncommon anomalies and have been rarely documented. Moreover, association between syndactyly and brachydactyly has still not been reported.

The Yunis-Varón syndrome represents a rare autosomal recessive syndrome of easy recognition characterized by defective growth of the cranial bone along with complete or partial absence of the clavicles (cleidocranial dysplasia), absence of thumbs and halluces, distal aphalangia, ectodermal anomalies, growth retardation and poor outcome. The molecular genetic basis is unknown. Here, we report an 8 months old girl with Yunis-Varón syndrome, born to a consanguineously married, with normal parents. She had micrognathia, wide fontanels, prominent eyes, poor sucking, congenital heart diseases, asymmetric face, ambiguous genitalia, reduction anomaly in right hand including thumb, and hypoplastic distal phalanges of 3th fingers, and hypo plastic clavicles. She has glaucoma and lenses opacity. There is another similar case in her family. Karyotype is normal. She is the first Iranian known case of Yunis-Varón syndrome.

Congenital limb deformities are rarely reported in the cat. The macroscopic and radiographic features of aphalangia are described in a 2-month-old male kitten showing a shortened limb that ended, at the level of the carpus, in a stump without digits. A nail was present at the level of the first phalanx and on the palmar surface only two footpads were present. The radiographs showed an absence of phalanges. The first metacarpal and the proximal and distal phalanges of digit 1 were present. The deformed metacarpal bones were reduced in length; the carpal bones were incompletely ossified. This defect is a rare condition in many animal species. To the author's knowledge, the congenital fore limb deformity described here is the first documented case in a cat.

The Yunis-Varón syndrome (YVS) represents a rare autosomal recessive syndrome of easy recognition characterized by cleidocraneal dysplasia, absence of thumbs and halluces, distal aphalangia, ectodermal anomalies, and poor outcome. Here, we report two sisters with YVS who also had papillo-macular atrophic chorioretinopathy with "salt-and-pepper" appearance that could not be attributed to environmental or metabolic causes. Our best hypothesis is that the ocular findings in our two patients are part of the phenotypic manifestations of YVS. We suggest that an extensive ophthalmologic examination should be carried out in all children with YVS in order to define the frequency and nature of the ocular findings in these patients.

The results of 21 non-vascularized toe phalanx transfers in 13 patients were reviewed radiologically with respect to function, physeal patency, growth and donor site morbidity at a mean follow-up of 7.4 (range 2.9-13.6) years. Physeal patency was maintained in 4 of 18 surviving transfers. The length of the transferred phalanx averaged 75% of the contralateral comparable toe phalanx and 44% of the contralateral digit proximal phalanx. Most patients had good or simple use of the hand with active joint motion. There was universal shortening of the donor toe with hypoplasia of the middle and distal phalanges. This review suggests that transfer of a non-vascularized toe phalanx provides a reliable but limited means for increasing length of a digit, stabilizing soft tissue "nubbins" and improving function. Longer follow-up has shown more modest gains in growth than in some previous reports.

Many options of varying complexity are available for the management of congenital short digits resulting from aphalangia in symbrachydactyly and constriction ring syndrome. We have used non-vascularized free toe phalanx transfers for these children when a vascularized toe transfer has been contraindicated. We describe our technique and experience with 22 children who underwent a total of 64 transfers of the proximal (35) or middle (29) toe phalanges (average 3 per child). The mean age at initial surgery was 15 months, and the mean follow-up was 5 years. Duration of time until epiphyseal closure could not be determined accurately, but total digital elongation averaged 6mm. Complications of this technique include joint instability, premature epiphyseal closure and, in one patient, infection and graft loss. Donor site deformity was determined according to measured growth deficit and toe function. This technique is a simple option for digital elongation and, if performed in the appropriate age group in short fingered and monodactylous subtypes of symbrachydactyly, has the potential to allow growth and function with minimal donor site deficit.