Akademik Veri Yönetim Sistemi
58th Annual Meeting of European Society for Paediatric Endocrinology (ESPE), Vienna, Avusturya, 19 - 21 Eylül 2019, cilt.1, sa.1, ss.452
Background: 3-M syndrome is an autosomal recessive growth
disorder characterised by severe prenatal and postnatal growth retardation
caused by mutations in CUL7,OBSL1 or CCDC8.Clinical
characteristics include dysmorphic facial features and skeletal
abnormalities.
Aim: Evaluation of clinical and molecular findings and the effect
of growth hormone (GH) threrapy in seven patients with 3-M
syndrome from five different families.
Patients and Methods: Clinical and laboratory findings of seven
patients(4males,3females) from 5 different families[Family(F)
I(Patient(P)1,P2), FII(P3,P4),FIII(P5),FIV(P6),FV(P7)] were
evaluated retrospectively. Pituitary function, GH stimulation and
IGF generation tests were recorded.Growth and pubertal features
were evaluated at follow-up.
Results: Median (range) age of the patients was 6.5(0.5-16.6)
years,4 males(P1, P2,P6,P7), 3 females(P3,P4,P5). There was
consanguinity in three families(FI, FII, FIV). Six cases(85.7%)
were low birth-weight SDS was -3.1[(-1.4)-(-5.1)]. All patients
presented with severe growth-retardation; median (range)
height SDS was -5.3[(-3.9)–(-7.9)],BMI SDS was -0.8[(-2.4)–
(1.5)], head-circumference SDS was 1.4[(-0.17)–(-2.5)]. All patients
had dysmorfic features related to 3-M syndrome. All patients’
bone-age were delayed.CUL7gene mutations were found
in FI(homozygous;p.731insGlufs) and FV(novel, compound
heterozygous;p.Pro1511Ser/p.Arg1528Ter),OBSL1 gene mutations
(homozygous;p.Thr425Asp) were found in FII and FIII.
Family IV’s molecular analysis has not been completed yet. GH
response in stimulation tests were normal in P4,P5,P7, high in
P1,P2,P3 and low in P6. Five patients except(P1 and P7) were
started GH treatment.Median of GH treatment duration was 1.9
years(0.1-4.3). Response to GH treatment was insufficient in all
five patients. Patient 1 was 16.6 years-old at presentation while his
pubertal-stage was Tanner-II and delayed. At recent evaluation
he was 18.6 years-old and pubertal-stage was Tanner-III and puberty
has not completed yet. Patient 6’s puberty started at age 13.5
however progressing slowly, evaluation at age 17.1 his pubertal
stage was Tanner-III and hormone levels were indicating partial
primary hypogonadism. Recently, all female patients and P7 are
below ten years of age and prepubertal. P2 is 13.1 years-old and
prepubertal.
Conclusion: 3-M syndrome should be considered in differential
diagnosis of patients with severe prenatal and postnatal growth
retardation.Children with 3-M syndrome are treated with GH but
there is lack evidence of efficacyin literature. Insufficient response to GH treatment and high levels of GH in tests might indicate GH
resistance and IGF1 receptor resistance.3M syndrome might cause
delayed puberty and partial primer gonadal insufficiency in boys