Endocrine Abstracts

Introduction: Underlying causes of short stature are difficult to establish and many patients with short stature do not have a clear diagnosis. Careful examination and investigation of patients with short stature may identify additional features that help to make a diagnosis or direct genetic testing. Here we describe a patient with severe short stature with additional features on examination and skeletal survey in keeping with KBG syndrome. In addition, the patient developed CPP which is a rarely reported feature of KBG syndrome. KBG syndrome is most frequently caused by mutations in ANKRD11. The most significant features include developmental delay, skeletal abnormalities (typically costovertebral abnormalities) and abnormal facies (macrodontia, craniofacial abnormalities and low hairline). We present a patient with a rare mutation in ANKRD11 with typical skeletal abnormalities and central precocious puberty (CPP).

Case presentation: A 5-year-old girl was referred for short stature with a background of autism, severe learning disability, sleep disturbance, bilateral hearing loss, constipation and abnormal hand movements. Birth weight was 3.2 kg. Height was 96.9 cm (-2.2 SDS), weight 14.8 kg (+0.2 SDS), BMI 15.8. Additional features included bilateral clinodactyly, foetal finger pads, broad toes, low hair line, mid facial hypoplasia, short neck, simple ears and macrodontia. Skeletal survey revealed wormian bones, bilateral cervical ribs, and macrodontia. Bone age was delayed by 2.5 yrs. Genetic testing revealed a previously described ANKRND11 variant c.1903_1907del; p.(Lys635Glyfs*26). She then developed into puberty before age 8 years. LHRH test at 8.7 years showed a LH peak 6.3 IU/l, FSH peak 9.3 IU/l, in line with CPP. She commenced on GnRH-analogues.

Conclusion and learning points: ANKRND11 is a chromatin modulator affecting growth by increasing P21, a cell cycle inhibitor. The role of ANKRD11 in pubertal development is unknown. This case highlights features that direct clinicians towards a diagnosis of KBG syndrome, including macrodontia, costovertebral abnormalities. CPP has been described rarely in patients with KBG syndrome but can be added to features that may help to direct to a diagnosis of KBG syndrome. Other syndromes with short stature and early puberty include Temple syndrome and Williams Syndrome.