Dominant inheritance of cerebral gigantism

doi:10.1016/S0022-3476(77)80822-6

The Journal of Pediatrics

Volume 91, Issue 2, August 1977, Pages 251-256

https://doi.org/10.1016/S0022-3476(77)80822-6 Get rights and content

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.

References (20)

HookEB et al.
Cerebral gigantism: Endocrinological and clinical observations of six patients including a congenital giant, concordant monozygotic twins, and a child who achieved adult gigantic size
J Pediatr
(1967)
BejarRL et al.
Cerebral gigantism—concentrations of amino acids in plasma and muscle
J Pediatr
(1970)
JonesKL et al.
Older paternal age and fresh gene mutation: Date on additional disorders
J Pediatr
(1975)
SotosJF et al.
Cerebral gigantism in childhood
N Engl J Med
(1964)
JaekenJ et al.
Cerebral gigantism syndrome—a report of four cases and review of the literature
Z Kinderheilk
(1972)
OttJE et al.
Cerebral gigantism
Am J Dis Child
(1969)
HooftC et al.
Gigantism cerebral familial
Acta Paediatr Belg
(1968)
MaceJW et al.
Cerebral gigantism—triad of findings helpful in diagnosis
Clin Pediatr
(1970)
AbrahamJM et al.
Soto's syndrome of cerebral gigantism
Arch Dis Child
(1969)
StephensonJN et al.
Cerebral gigantism
Pediatrics
(1968)

There are more references available in the full text version of this article.

Cited by (44)

Overgrowth with and without obesity: Clinical and molecular principles
2012, Anales de Pediatria
Los hipercrecimientos somáticos conforman una patología compleja, heterogénea y conocida parcialmente, si bien el incremento en nuestros conocimientos en biología molecular está posibilitando descubrir las bases etiológicas de muchos de los cuadros clínicos responsables. El diagnóstico diferencial de un paciente con una posible variante de la normalidad, una cromosomopatía, un síndrome dismórfico, una metabolopatía o una endocrinopatía, es esencial. La aproximación clínica inicial debe incluir una correcta anamnesis y examen físico, así como la solicitud de unas pruebas complementarias analíticas y de imagen que ayuden a orientar el diagnóstico. En efecto, es necesario practicar hemograma y bioquímica completos, determinar los niveles de IGF-I e IGFBP-3, T4 libre, TSH y homocistinuria, así como efectuar un cariotipo y una radiografía de mano y muñeca izquierdas. Sus resultados deben orientarnos ampliamente en el enfoque del paciente. La realización adicional de estudios moleculares, cuando se sospeche una enfermedad monogénica, y la necesidad de practicar estudios cardiológicos, oftalmológicos, esqueléticos, psicológicos y paidopsiquiátricos, deberá efectuarse cuando proceda a la luz de la información clínica y de los estudios complementarios antes comentados.
En esta revisión se analizarán las bases etiológicas y los fundamentos diagnóstico-terapéuticos de las principales causas de hipercrecimiento.
Somatic overgrowth is a complex and heterogeneous pathology that is only partially understood, although developments in molecular biology have allowed the discovery of the aetiological basis of some of these conditions. The differential diagnosis of a patient with a possible variant of normality, a chromosomopathy, a dysmorphic syndrome, a metabolic or an endocrine disease is essential. The initial clinical evaluation should include a correct anamnesis and physical examination, as well as complementary laboratory and image analyses that will help to orient the diagnosis. This should include a full blood counts and complete biochemical analysis, determinations of IGF-I, IGFBP-3, free T4, TSH and homocystinuria, as well as a karyotype and an X-ray of the left hand and wrist. These results should be very beneficial in orienting the diagnosis. Additional molecular studies should be performed when a monogenic disease is suspected. Cardiological, ophthalmological, skeletal, psychological and psychiatric studies should be performed if the clinical information and previously mentioned complementary studies so indicate.
In this review, the aetiological basis and the diagnostic-therapeutic principles in the most common causes of overgrowth, will be analysed.
Overgrowth Disorders Associated with Tall Stature
2008, Advances in Pediatrics
Citation Excerpt :
A genetic cause was suspected for a long time. Several families with members affected in two or three generations were reported, suggesting autosomal dominant inheritance [95]. Most of the cases are sporadic (85%), but could be a result of new mutations, most frequently in the paternal chromosome.
Accelerated linear growth and advanced bone age in Sotos syndrome is not associated with abnormalities of collagen metabolism
1998, Clinical Biochemistry
Objectives: To investigate whether the advanced bone age in Sotos syndrome is associated with alterations in type I collagen metabolism in bone.
Design and methods: The metabolism of collagen was studied by analyzing the production, gene expression and degradation of type I collagen in dermal fibroblast strains from patients with Sotos syndrome and comparing them with fibroblasts from age-matched healthy subjects. Collagen production was determined as collagenase digestible radioactivity and collagen mRNA levels were measured by RT-PCR. Collagen degradation was assessed by specific collagenase assay and gelatin zymography. To determine the structural defects in type I collagen, the newly synthesized proteins were analyzed by SDS-PAGE before and after proteolytic digestion with pepsin.
Results: In the present study, we have demonstrated that the collagen production, secretion and degradation in Sotos syndrome is comparable to controls. In addition, no qualitative differences in mRNA transcripts for type I collagen were detected between the control and Sotos syndrome fibroblasts. The secretion and intracellular accumulation of procollagen is also comparable to controls. The analysis of both procollagen and collagen on SDS-PAGE did not exhibit any major structural changes as compared with controls.
Conclusions: Our results on several aspects of collagen metabolism have demonstrated for the first time that collagen, the most abundant of mammalian proteins and the major constituent of bone, is normal in patients with Sotos syndrome. Therefore, it appears that the advanced bone age and accelerated linear growth seen in patients with Sotos syndrome may not be attributed to inherent abnormalities of collagen metabolism. The etiology and the pathogenesis of Sotos syndrome still remains unclear.
Screening for Wilms tumor in high-risk individuals
1995, Hematology/Oncology Clinics of North America
Clinicians have long recognized the syndromic association between Wilms tumor and a variety of genetic disorders. The recent identification of molecular mechanisms associated with the development of certain Wilms tumors may allow for precise identification and improved tumor screening for high-risk individuals. This article reviews the clinical and molecular features associated with Wilms tumor in addition to the introduction of strategies guiding its surveillance. The implementation of presymptomatic tumor surveillance in high-risk individuals should lead to early diagnosis and treatment of Wilms tumor.
Case report: Dominantly inherited childhood gigantism resembling Sotos' syndrome
1989, American Journal of the Medical Sciences
Excessive growth in infancy and onset of puberty at age four was observed in a boy with features resembling Sotos syndrome. Early development of secondary sexual characteristics and advanced osseous maturation were observed. The family history was significant; excessive weight gain tended to occur in female family members in association with rapid growth in infancy and childhood. A delayed insulin response to glucose was observed in both mother and sister, and diabetes developed during his mother’s gestation. These observations suggest that undetermined factors associated with excessive growth may be inherited as a dominant trait with variable expression.
Tall stature in children and adolescents
2020, Minerva Pediatrica

View all citing articles on Scopus

^**

Presented in part at the 1975 Birth Defects Conference, Kansas City, Mo.

Studies at Harbor General Hospital were supported by USPH RRO 0425 and HD-05624 and Birth Defects Center and research grants from the National Foundation-March of Dimes, and the Easter Seal Research Foundation.

Studies at the Children's Hospital, Columbus, Ohio were supported by the John W. Champion Center.

Studies at the University of Arkansas were supported by United States Public Health Service grant AM 15901 and CA 13907.

¹: Dr. Zonana was supported by a National Foundation-March of Dimes Postdoctoral Fellowship and United States Public Health Service Research Training Grants (5 T01-HD 00417-03 and 5 T22-DE 00102-02).

View full text

Original articleDominant inheritance of cerebral gigantism**

J Pediatr

J Pediatr

J Pediatr

Cerebral gigantism in childhood

N Engl J Med

Cerebral gigantism syndrome—a report of four cases and review of the literature

Z Kinderheilk

Cerebral gigantism

Am J Dis Child

Gigantism cerebral familial

Acta Paediatr Belg

Cerebral gigantism—triad of findings helpful in diagnosis

Clin Pediatr

Soto's syndrome of cerebral gigantism

Arch Dis Child

Cerebral gigantism

Pediatrics

Original article
Dominant inheritance of cerebral gigantism**