ESPE Abstracts

Introduction: Brachydactyly mental retardation syndrome (BDMR, #MIM600430) is a rare genetic disorder caused by deletions in 2q37 region, characterised by intellectual disability, facial features, and skeletal abnormalities. This case delineates the clinical progression and growth hormone (GH) therapy response of a patient with a unique phenotype resulting from an unbalanced derivative of a paternal balanced translocation, leading to a 2q37 deletion and 14q32 duplication.

Case Report: A 10-year-old female patient was referred for short stature, facial dysmorphism, psychomotor developmental delay, and bilateral shortening of metatarsal IV. She had proportionate short stature, having a height SDS of -2.5. In addition to facial dysmorphism, skeletal abnormalities were observed: a short thorax, pectus carinatum, bilateral genu valgus, bilateral shortening of the metatarsals IV, suggestive of brachydactyly type E, and bilateral partial 2-3 cutaneous syndactyly. Since the parathormone, vitamin D levels, and Guanine Nucleotide binding protein Alpha Stimulating gene analysis were normal, pseudo-hypoparathyroidism was excluded. Chromosome analysis revealed 46, XX karyotype. Affymetric Cytoscan (315K) microarray detected 3844 kb deletion at 2q37.3 and 6122 kb duplication at 14q32.2q32.33 as arr[hg19] 2q37.3(238,938,999-242,783,384) x1,14q32.2q32.33(101,163,429-107,285,437)x3. Subtelomeric fluorescence in situ hybridisation (FISH) analysis confirmed chromosome 2 and 14 abnormalities. The microdeletion region 2q37.3 also involved the histone deacetylase 4 (HDAC4,#MIM605314) gene. Maternal and paternal FISH analyses revealed the paternal karyotype was compatible with balanced translocation carriage as 46, XY t(2;14)(q37.3;q32.2). Our case is an unbalanced product of paternal balanced translocation carriage of chromosomes 2 and 14. At 12^6/12 years, the patient’s growth velocity was low (3.9 cm/year). GH tests with clonidine revealed a peak of 4.15 ng/mL and 4.84 ng/mL. Partial growth hormone deficiency was diagnosed. She received growth hormone therapy for 1.5 years, gaining 0.76 SDS in the first year, and discontinued at age 14.

Conclusion: Clinicians should consider BDMR syndrome a differential diagnosis when encountering clinical features resembling the AHO phenotype. This case study marks the first instance of alopecia totalis in BDMR syndrome, expanding the phenotypic spectrum beyond the previously reported sparse and uncombable hair. In addition, it should be kept in mind that BDMR syndrome may also cause GH deficiency, which warrants further investigation, given the potential for positive therapeutic outcomes.