Familial congenital choanal atresia with GATA3 associated hypoparathyroidism-deafness-renal dysplasia syndrome unidentified on auditory brainstem response.

Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder primarily caused by GATA3 haploinsufficiency and is challenging to diagnose in early childhood. We report a Japanese family with HDR syndrome and congenital choanal atresia. The 6-year-old female proband was diagnosed with epilepsy at the age of three. Under carbamazepine monotherapy, the patient presented hypoparathyroidism accompanied by severe hypocalcemia. Subsequently, renal ultrasound analysis revealed bilateral multicystic dysplastic kidneys. Because she had difficulty hearing, we sequenced GATA3 and determined that she had a c.708_709insC (p.Ser237Glnfs*66) allelic variant in exon 3. As a result, we found a family of this disease. Each family member, including her grandfather, mother, and two siblings, had HDR syndrome of varying clinical penetrance. We found a craniofacial anomaly, congenital choanal atresia, which was inherited as an autosomal dominant trait. Hypocalcemia coupled with vitamin D deficiency, triggered by carbamazepine treatment, ultimately revealed the proband's childhood- onset HDR syndrome. Pure-tone audiometry revealed different severities of deafness as well as the progression of sensory hearing loss. However, auditory brainstem response for hearing screening is probably insufficient for ascertaining HDR syndrome in the early stages of life. We presented new clinical clues to diagnose the HDR syndrome.

Ring/marker chromosome derived from chromosome 7 in childhood acute megakaryoblastic leukemia with monosomy 7.

In some cases of childhood acute megakaryoblastic leukemia (AMKL), G-band analysis reveals supernumerary ring/marker chromosomes along with monosomy 7. However, their origin and relevance are poorly understood. We experienced three patients with AMKL, one of whom had Down's syndrome, whose blasts at the first visit exhibited both monosomy 7 and a ring/marker chromosome. For one case, precise molecular-cytogenetic techniques revealed that the ring chromosome was derived from a chromosome 7. It was strongly suggested that the ring chromosome was derived from a chromosome 7 in another case. The ring or one of the 2 marker chromosomes was derived from a chromosome 7 in the other case. All patients responded well to initial induction therapy. While it is not clear whether the ring/marker chromosome 7 affects the long-term prognosis of acute myeloid leukemia with monosomy 7, it may be of prognostic relevance to distinguish pure monosomy 7 from monosomy 7 with a ring/marker chromosome 7. For this purpose, conventional G-banding could be complemented with additional techniques such as spectral karyotyping or fluorescence in situ hybridization, which characterize the aberration in more detail. These methods may be useful for determining the optimal treatment and for elucidating the etiology of AMKL itself.