Split hand/foot malformation with long bone deficiency associated with BHLHA9 gene duplication: a case report and review of literature

Chamara Sampath PaththinigeEmail author View ORCID ID profile,
Nirmala Dushyanthi Sirisena,
Fabienne Escande,
Sylvie Manouvrier,
Florence Petit and
Vajira Harshadeva Weerabaddana Dissanayake

BMC Medical Genetics201920:108

https://doi.org/10.1186/s12881-019-0839-2

Received: 11 February 2019
Accepted: 3 June 2019
Published: 14 June 2019

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Abstract

Background

Split hand/foot malformation (SHFM) is a group of congenital skeletal disorders which may occur either as an isolated abnormality or in syndromic forms with extra-limb manifestations. Chromosomal micro-duplication or micro-triplication involving 17p13.3 region has been described as the most common cause of split hand/foot malformation with long bone deficiency (SHFLD) in several different Caucasian and Asian populations. Gene dosage effect of the extra copies of BHLHA9 gene at this locus has been implicated in the pathogenesis of SHFLD.

Case presentation

The proband was a female child born to non-consanguineous parents. She was referred for genetic evaluation of bilateral asymmetric ectrodactyly involving both hands and right foot along with right tibial hemimelia. The right foot had fixed clubfoot deformity with only 2 toes. The mother had bilateral ectrodactyly involving both hands, but the rest of the upper limbs and both lower limbs were normal. Neither of them had any other congenital malformations or neurodevelopmental abnormalities. Genetic testing for rearrangement of BHLHA9 gene by quantitative polymerase chain reaction confirmed the duplication of the BHLHA9 gene in both the proband and the mother.

Conclusions

We report the first Sri Lankan family with genetic diagnosis of BHLHA9duplication causing SHFLD. This report along with the previously reported cases corroborate the possible etiopathogenic role of BHLHA9 gene dosage imbalances in SHFM and SHFLD across different populations.