Fraternal Twins with Likely Split Hand/Split Foot Malformation (SHFM)

1. History: A pair of dizygotic male/female twins were born at term with congenital bilateral limb abnormalities and classic "claw-like" hands and feet. A fetal ultrasound showed clubbed feet in Twin A and missing digits in Twin B. Pregnancy history is significant for gestational diabetes requiring insulin. The mother did not take any other medications during pregnancy. There is a paternal family history of limb abnormalities, including the father, who was born with clubfoot and limb length issues. Given the associated skeletal abnormalities in fraternal twins with significant family history of club feet, a genetic condition was strongly suspected.
2. Physical exam findings: Twin A (boy) was born with ectrodactyly of right hand with agenesis of the 3rd digit, lefttibial hypoplasia with malrotation at the knee and ankle, right foot ectrodactyly and left bifid foot. He was also found to have mild hypotonia on initial exam. Twin B (girl) was born with right hand ectrodactyly with agenesis of the 3rd digit, right foot syndactyly with agenesis of 2nd toe, and left foot ectrodactyly with agenesis of the 3rd digit. Neither baby showed craniofacial or spinal abnormalities.
3. Lab/Diagnostic imaging/Procedures: Cardiac ECHO and renal ultrasound showed no internal anomalies. Skeletal survey confirmed ectrodactyly and missing foot bones in both twins, and deformed tibia and absent fibula in twin A. Both twins had normal karyotype. Identical chromosomal abnormalities found on microarray confirmed SHFM type 1.
4. Final diagnosis: Split Hand Split Foot Malformation Type I
5. Discussion: 

    Split Hand/Split Foot Malformation (SHFM) is a rare condition characterized by complete/partial absence of some fingers and toes and clefts in hands and feet. SHFM can be due to autosomal dominant, X-linked recessive, or sporadic mutations. Patients with SHFM usually have normal development; however, there is rare incidence of deafness and intellectual disability.

    SHFM is even rarer in twins, demonstrated by only a few available studies. The twins are fraternal yet carry the same mutation, likely autosomal dominant transmission from their father. This genetic mutation has variable penetrance, as revealed in this case of SHFM with phenotypic differences noted between the father and even the twins themselves.

    These limb anomalies must be recognized promptly, in-utero or postnatally. SHFM may lead to normal life expectancy, but there is a risk of hearing loss, intellectual disability and need for orthopedic interventions. Ectrodactyly is associated with diseases such as ectrodactyly-ectodermal dysplasia clefting syndrome, Karsch-Neugebaeur Syndrome, or Roberts Syndrome; presenting with cleft lip/palate, orodental anomalies or multisystemic involvement, respectively. Multidisciplinary care is often needed due to effects on feeding and growth. If prenatally diagnosed, a thorough assessment must be completed postnatally to rule out other syndromes or other organ system involvement. Parents must be about immediate postnatal care and diagnostic testing as well as long term prognosis.

References:

1. Gane, B. D., & Natarajan, P. (2016). Split-hand/feet malformation: A rare syndrome. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943129/

2. Marcinowski, F. (n.d.). Roberts syndrome: Radiology Reference Article. Retrieved from https://radiopaedia.org/articles/roberts-syndrome?lang=us

3. Mathian, V. M., Sundaram, A. M., Karunakaran, R., Vijayaragavan, R., Vinod, S., & Rubini, R. (2012, August). An unusual occurrence of Karsch-Neugebauer syndrome with orodental anomalies. Retrieved August 2012, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467867/

4. Split Hand/Split Foot Malformation. (2004). Retrieved from https://rarediseases.org/rare-diseases/split-handsplit-foot-malformation/