Congenital malformations - Edocr

CHAPTER 50 HEMIHYPERPLASIA AND OVERGROWTH DISORDERS 351
and unilateral peripheral nerve enlargement
have also been reported. 9 Patients with central
nervous system (CNS) involvement are at risk of
developing seizures and mental deficiency. IHH
is assumed to be sporadic but familial cases have
been reported. 12 Hemihyperplasia occurs in approximately
13% of patients with BWS and it has
been suggested that infants with IHH represent
a partial or incomplete expression of BWS in
some cases. 9
EVALUATION AND MANAGEMENT
All infants suspected to have overgrowth syndrome
should have careful physical examination
to evaluate for associated major and minor anomalies.
It may be helpful to obtain a detailed family
history and to evaluate the parents and siblings of
the affected infant as well. There may be a significant
phenotype overlap between different
syndromes and an early genetic evaluation is
necessary in all cases. All four limb lengths and
circumferences should be measured accurately
to determine any asymmetry and for future comparison.
Blood sugar values should be monitored
closely for first 3–7 days as untreated hypoglycemia
is an important cause of developmental
delay in many infants with BWS. A baseline
skeletal survey for bone length, bone age, and
scoliosis; and abdominal ultrasound to evaluate
for visceromegaly, anomalies, and to exclude any
tumors should be done in all infants. An MRI of
brain should be considered in all infants if the diagnosis
is not clear or craniofacial asymmetry
with or without neurological signs is present.
Conventional cytogenetic analysis of peripheral
blood lymphocytes should be done in all
cases and high-resolution banding and in situ
fluorescence hybridization may be used in specific
cases. Further uniparental disomy analysis
and methylation analysis for BWS should be
done in consultation with a geneticist in all cases
suspected of BWS. Stratification of BWS cases
according to the methylation pattern, also referred
to as epigenotyping, can help in predicting the
risk for future tumor development. 13,14 The affected
children, particularly patients with IHH,
require regular orthopedic follow-up to monitor
for limb length discrepancies and associated scoliosis
and gait abnormalities. Infants with
medullary sponge kidneys will require monitoring
of their renal function every 6 months and
periodic nephrology follow up as necessary.
PROGNOSIS
The long-term prognosis will depend on the underlying
disorder and the presence or absence of
associated congenital anomalies. Patients with
isolated hemihyperplasia with no associated congenital
malformations are likely to have an average
life span. 9 The cognitive outcome of infants
with overgrowth disorders is primarily related to
the underlying syndrome and was reviewed in a
recent article by Cohen. 15 The cognitive outcome
of infants with BWS, the most common cause of
generalized overgrowth in the newborn, correlates
more to their neonatal course and episodes
of untreated hypoglycemia. Patients with craniofacial
anomalies and hemimegalencephaly are at
higher risk of developmental delays.
RISK OF NEOPLASMS IN
OVERGROWTH SYNDROMES
Several reports have confirmed a significantly
higher risk of neoplasms in infants with overgrowth
syndromes. Overgrowth disorders are
characterized by dysregulation of normal cellular
growth-control mechanisms and it has been
proposed that the same abnormalities also predispose
these patients to future development of
neoplasms. These tumors may be present at
birth or may develop during childhood. The
greatest risk for tumor development is in early
childhood. The incidence of tumor development
in BWS and IHH has been reported to be
about 7.5% and 5% respectively, which is several
hundred times higher than the incidence of