Endocrine Abstracts

JOINT2758

Introduction: Cranio-lenticulo-sutural dysplasia (CLSD), also known as Boyadjiev-Jabs syndrome (ORPHACODE 50814), is a rare disorder characterized by large, late-closing fontanelles, hypertelorism, early-onset cataracts, and skeletal dysplasia. It is primarily inherited in an autosomal recessive manner, though rare autosomal dominant cases have been reported.

Case Report: An 11-year-old male was referred for short stature evaluation. His height was 130.1 cm (<3rd percentile, –2.66 SD), with a growth velocity of 3.5 cm/year (9th percentile). He had a proportionate body structure, normal head circumference (51.5 cm, 10th percentile), and delayed bone age (by ~3 years). Pubertal stage was Tanner P1G1. Born SGA (2480 g, <10th percentile) at 39 weeks via emergency cesarean section, he had cryptorchidism with a right inguinal hernia (surgically corrected at 10 months) and congenital heart defects (ASD and VSD), which closed spontaneously by age four. His cranial fontanelles closed at nine years. Facial dysmorphisms included a prominent forehead, hypertelorism, and low-set ears, with skin hyperpigmentation and a frontal hemangioma. He exhibited mild psychomotor developmental delay (PMDD) with muscular hypertonia, dystonic movements, and facial tics. Due to PMDD, brain and spinal MRI was conducted, revealing an empty sella and a small osteoangioma at D3. However, FRAXA analysis, array-CGH, plasma and urinary amino acid profiles were all within normal limits. Regarding his proportionate short stature associated with empty sella, routine blood tests, celiac serology, pituitary hormone profile, and sweat test were performed, all yielding normal results except for a low IGF-1 level for age. The patient subsequently underwent an arginine stimulation test, which demonstrated a normal GH peak (9.7 ng/ml). Whole exome sequencing ultimately identified a de novo heterozygous missense variant, c.2146C>T (p. Arg716Cys), in the SEC23A gene (14q13-q21), classified as likely pathogenic (Class 4). Given his syndromic short stature, SGA birth without catch-up growth, he recently started recombinant human GH (rhGH) at 30 mg/kg/day, with treatment ongoing.

Conclusions: This case presents notable features, including the autosomal dominant inheritance of cranio-lenticulo-sutural dysplasia and the ongoing treatment with rhGH, which has not been previously reported in the literature for this rare disorder. This highlights the importance of comprehensive genetic investigations in patients with suspected syndromic short stature.