ABSTRACT
We describe a male patient with dual genetic diagnoses of atypical hand-foot-genital syndrome (HFGS) and developmental delay. The proband had features of HFGS that included bilateral vesicoureteric junction obstruction with ectopic ureters, brachydactyly of various fingers and toes, hypoplastic thenar eminences, and absent nails on both 4th toes and right 5th toe. The atypical features of HFGS present were bilateral hallux valgus malformations and bilateral preaxial polydactyly of the hands. Chromosomal microarray analysis identified a de novo 0.5 Mb deletion at 2p16.3, including the first four exons of the NRXN1 gene. Whole exome sequencing and subsequent Sanger sequencing identified a de novo missense mutation (c.1123G>T, p.Val375Phe) in exon 2 of the HOXA13 gene, predicted to be damaging and located in the homeobox domain. The intragenic NRXN1 deletion is thought to explain his developmental delay via a separate genetic mechanism.
Subject(s)
Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Cell Adhesion Molecules, Neuronal/genetics , Developmental Disabilities/diagnosis , Developmental Disabilities/genetics , Foot Deformities, Congenital/diagnosis , Foot Deformities, Congenital/genetics , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/genetics , Homeodomain Proteins/genetics , Mutation , Nerve Tissue Proteins/genetics , Urogenital Abnormalities/diagnosis , Urogenital Abnormalities/genetics , Calcium-Binding Proteins , Child, Preschool , Computational Biology/methods , DNA Copy Number Variations , DNA Mutational Analysis , Exome , High-Throughput Nucleotide Sequencing , Humans , Male , Neural Cell Adhesion Molecules , Phenotype , Polymorphism, Single NucleotideABSTRACT
A twin pregnancy with a coexisting complete hydatiform mole and a healthy fetus is rare. Associated with this condition are potentially serious maternal and fetal complications. We describe a case of a woman, 23/40 pregnant, who was diagnosed with a twin pregnancy complicated by a hydatiform mole, vaginal bleeding, hyperthyroidism and preterm labour at 26/40. Her hyperthyroidism was successfully treated with propylthiouracil. The preterm labour resulted in the livebirth of a healthy male infant. The baby developed biochemical hypothyroidism post-natally. The baby's thyroid function tests were unexpected, revealing a low T4 and a low-normal thyroid stimulating hormone. This is the first case reported in the literature to describe an infant's clinical and biochemical thyroid status after gestational trophoblastic disease complicated by hyperthyroidism.