IMPE Abstracts

Background: 2q37 deletion syndrome is a rare chromosomal abnormality (OMIM #600430) also called brachydactyly mental retardation syndrome (BDMR), or Albright Hereditary Osteodystrophy-like syndrome (AHO). It is characterized by a wide spectrum of clinical findings including mild to moderate psychomotor developmental delay/intellectual disability, brachydactyly type E, short stature, obesity, hypotonia, characteristic facial dysmorphism, hypermobility /joint dislocation and scoliosis. The association with Parathyroid hormone (PTH) resistance it is rarely described. In recent years, small subgroups of patients with inactivating PTH/PTHrP signaling disorders (iPPSDs) without known molecular defects have been re-diagnosed as affected by the 2q37 microdeletion syndrome.

Case report: A 7.8 year old girl was admitted to our department for diagnostic evaluation. She was born full term (39 weeks) after an uneventful pregnancy, with adequate weight for gestational age (3550 grams). She had history of hospitalization in Neonatology for 7 days due to hypoglycemia and hypocalcemia. Family history was unremarkable. At 15 months old she was referred to Genetics department due to developmental delay and dysmorphia (low-set alar ears, left palpebral ptosis, hypotelorism, slight hypotonia). Karyotype showed a terminal deletion in the long arm of chromosome 2 at 2q37.1 region (46,XX,del(2)(q37.1)[20]). Both parent’s karyotype was normal, so the chromosomal abnormality was de novo. First evaluation by local endocrinology was at 5 years old when she was diagnosed with primary autoimmune hypothyroidism. During follow-up, elevated PTH values were observed. Physical examination at first consultation in our department revealed Height 132.3 cm (+1.6 SDS), Weight 44.6 Kg (+4.3 SDS), BMI 25.4 (+3 SDS). Obesity with moderate psychomotor developmental delay. Biochemical data showed normal renal function, hypocalcemia (7.6 mg/dl), hyperphosphatemia (7.6 mg/dl), elevated Alkaline Phosphatase (469 UI/L) and PTH (1023 pg/ml) levels consistent with PTH resistance. X rays showed advanced bone age (11 years) with a short 4^th metacarpal and signs of hyperparathyroidism on the skull (diploe thickening and absence of lamina dura). She was clinically asymptomatic and started oral treatment with calcium and calcitriol with good response.

Conclusion: After the exclusion of defects affecting PTH/PTHrP signaling pathway, screening for 2q37 deletion syndrome should be considered in the evaluation of patients with brachydactyly, mental and/or behavioral defects and elevated PTH serum levels. Further studies are needed to elucidate the clinical overlap between iPPSDs and BMDR syndrome in order to formulate a new classification algorithms for the early identification of these patients.