Discussion:
The diagnosis of PHS is usually
suspected at a young age based on the association of polydactyly and
hypothalamic hamartoma [1,5-9]. However, due to its extreme
rarity, the diagnosis may be unrecognized for a long time.
Endocrine manifestations can then be in the foreground and reveal the
diagnosis as was the case for our patient who presented with an adrenal
crisis. Adrenal insufficiency is in most cases linked to a hypothalamic
hamartoma which is noted in 90 to 100% of cases of PHS [4,9]. Cases
of congenital adrenal hypoplasia have also been reported [8,9]. J G
Hall’s review reports two PHS cases of death at birth secondary to
adrenal insufficiency [10]. Hypothalamic hamartoma leads to one or
more pituitary axes deficiencies. However, corticotropin deficiency
seems rare in this syndrome, especially in familial forms [8].
Growth hormone deficiency appears to be the most common pituitary
deficiency, but short stature in PHS may also be the result of
intrauterine growth retardation [9]. Panhypopituitarism has only
been reported in one case [9]. For our patient, it is not clear if
pituitary deficiencies were secondary to the hamartoma or to the
hypothalamic-pituitary surgery.
It should also be noted that the characteristics of hamartoma in PHS
differ from those of non-syndromic hamartomas. Epilepsy, behavioral
disturbances and gelastic seizures are less common in PHS and respond
better to treatment if they are present [8, 11,12]. Our patient had
no history of seizures and had no behavioral disturbances. Precocious
puberty can also reveal hamartoma. Its prevalence seems to be less
important in hamartomas associated with PHS than in non-syndromic
hamartomas [11]. Asymptomatic hamartoma detected incidentally on
imaging have also been reported [13]. Thus, hamartomas in PHS
usually only require monitoring and surgery is usually not indicated.
The diagnosis of PHS requires screening for associated abnormalities. A
bifid epiglottis was found on the otolaryngology examination of our
patient. This malformation is present in 40 to 100% of cases in PHS and
is most often asymptomatic [8,9,13-15]. However, some patients
present with more severe posterior laryngeal clefts, leading to
potentially fatal respiratory failure [1,8]. Bifid epiglottis is a
rarely isolated birth defect, and its detection should suggest the
diagnosis of PHS [14]. Heart, lung, and kidney malformations have
also been reported in PHS. Cardiac, abdominal, and renal ultrasound were
normal in our patient. Urogenital abnormalities are reported in almost
half of cases such as micropenis, hypospadias and uterovaginal aplasia
[4, 9]. The micropenis in the present case can be related to the
syndrome but can also be explained by congenital hypogonadotropic
hypogonadism.
The management in the present case will be limited to hormonal
replacement therapy. The delay in the diagnosis and management of growth
hormone deficiency has compromised the final height of the patient. An
early treatment with growth hormone may have given him normal growth.
Galasso et al . described a case of a PHS boy treated from the age
of 3 years and for 7 years with growth hormone. His final height was 5.5
cm above his target height [16].