Endocrine Abstracts

Case history: A fifteen year old female was seen in general paediatric clinic after multiple GP attendances based upon persistent maternal concerns for short stature (height below 0.4th centile). She was otherwise healthy, had achieved menarche at age 14, and had no dysmorphic features. She had been reviewed by endocrinology age ten and discharged with a diagnosis of familial short stature. Her mother’s height was on the 0.4th centile and her father’s on the 75th, resulting in a target range of 9th–91st centiles. Both of her siblings, females aged six and 11 years, were following the second centile for height.

Investigations: Karyotype and array comparative genomic hybridization demonstrated a female karyotype with unbalanced derivative chromosome X from an apparent translocation between the short arm of the X chromosome (Xp) and the short arm of chromosome 3. This abnormality results in loss of the SHOX gene and is consistent with variant Turner syndrome. The patient’s mother and siblings had identical translocations. Her father’s genetic analysis was normal. All three children had normal renal ultrasounds and echocardiograms as part of Turner syndrome surveillance.

Results and treatment: The patient and her family expressed disappointment that the diagnosis was missed by the endocrinology team, and that as a result the window of opportunity for growth hormone had been lost. Her younger sisters were started on growth hormone at age six and 11 years with gain of one height centile at six month follow up. After multiple miscarriages thought to be related to the translocation, the parents are considering pre-implantation genetic diagnosis for future pregnancies.

Conclusions and points for discussion: Parents with genetic disorders causing short stature can pass these disorders to their children, which in this case led to an erroneous diagnosis of familial short stature. Variant Turner syndrome, unlike classical Turner syndrome, can be associated with normal fertility. The clinical consequences of missed diagnosis include missing the window of treatment with growth hormone, effects on fertility (male fetuses carrying the translocation are non-viable), and implications for diagnosis and screening of other family members. It is crucial to consider an underlying genetic diagnosis at an early stage, particularly if one parent has marked short stature themselves.