EYH Ng, JCK Chan, CFY Shih, SKL Ho, HM Luk

Case History

The proband is a 22-year-old gentleman. He was born full term to non-consanguineous Chinese parents with birth weight 2.55 kg. His body length at birth, as indicated on sex- and age-adjusted growth charts, fell between 3rd and 10th percentiles while his birth weight and head circumference were at 10th percentile. He was first assessed by Clinical Genetics at 4 years old for short stature, measuring 4 cm below 3rd percentile on sex- and age-adjusted growth charts. Throughout childhood, he experienced recurrent chest infections and easy bruising, and also had delayed teeth eruption. His cognitive development was all along normal.

Upon most recent assessment, his final adult height was 142.3 cm. He had multiple skeletal abnormalities affecting both the trunk and limbs including pectus excavatum, thoracic kyphosis, genu valgum, pes cavus and hallux valgus (Figure 1A-F). Skeletal survey at age 11 showed bilateral hip and knee metaphyseal dysplastic changes (Figure 1G). Magnetic resonance imaging (MRI) of the hips showed bilateral coxa vara and dysplastic capital physis with features of pre-slip capital femoral epiphysis. His bone age was all along not delayed.

He reported symptomatic steatorrhea following fatty meal and was prescribed regular Pancreatin supplement, which resulted in improvement. He had hypoamylasemia with amylase levels ranged from 11 to 14 U/L (reference interval: 25-101 U/L). Abdominal ultrasound showed hyperechoic pancreas and possible lipomatosis.

He experienced chronic thrombocytopenia since childhood with platelet counts ranging from 17 to 140 x 10/L (reference interval: 152-358 x 10⁹/L). His red and white blood cell counts have been intermittently low, with red blood cell counts ranging from 2.38 to 4.94 x 10¹²/L (reference interval: 4.3-5.7 x 10¹²/L) and white blood cell counts between 1.6 and 8.31 x 10⁹/L (reference interval: 3.9-10.7 x 10⁹/L).

Family history reveals that among three siblings, his eldest sister is similarly affected, presenting with metaphyseal chondrodysplasia, frontal bossing and pancytopenia; both parents and another elder sister remain asymptomatic.

Figure 1 Clinical photos of the proband. (A-B) Anterior and lateral facial profile (C-F) Multiple musculoskeletal abnormalities including pectus excavatum, thoracic kyphosis, genu valgum, pes cavus and hallux valgus (G) X-ray of bilateral hip with metaphyseal irregular striated sclerotic changes and mild flaring, partial vertebra with diffuse spinal end-plate irregularities but no scalloping or abnormal interpedicular distance.