Family History Of Short Stature Research Articles

Knowledge and Awareness for the Early Detection and Intervention of Short Stature among Families in Qassim Region 2021–2022: A Cross-Sectional study

Background: Short stature is a common reason for the referral of children to endocrinology clinics. A study in Saudi Arabia recorded a relatively high frequency of short stature among children and adolescents. This condition is multifactorial and can be influenced by genetic factors, environmental factors, or endocrine diseases. Early detection and intervention are crucial steps in the long-term outcomes and benefits.
 Aim: To evaluate the knowledge and awareness for the early detection and intervention of short stature.
 Methods: A cross-sectional study utilizing a representative random cluster sample of 384 participants living in various cities in the Qassim region, including Buraydah, Unaizah, Alrass, and Riyadh Al Khabra, and in places outside the central region from October 2021 to March 2022. To achieve our goals, we used a self-administered questionnaire that evaluated knowledge and awareness for the timely identification and intervention of short stature among families in the Qassim region.
 Results: We received 469 surveys. The overall mean knowledge score was 2.04 (SD 0.92), with poor and good levels of knowledge identified among 68.4% and 31.6%, respectively. Higher knowledge scores were associated with being married, having children, and having a family history of short stature.
 Conclusion: Based on our data, we conclude that the majority of Qassimi families have poor knowledge about the early detection and intervention of short stature.

The Spectrum of ACAN Gene Mutations in a Selected Chinese Cohort of Short Stature: Genotype-Phenotype Correlation.

Objective: Mutations in the ACAN gene have been reported to cause short stature. However, the prevalence estimates of pathogenic ACAN variants in individuals with short stature vary, and the correlation between ACAN genotype and clinical phenotype remain to be evaluated. To determine the prevalence of ACAN variants among Chinese people with short stature and analyze the relationship between genotype and main clinical manifestations of short stature and advanced bone age among patients with ACAN variants. Methods: We performed next-generation sequencing-based genetic analyses on 442 individuals with short stature. ACAN variants were summarized, previously reported cases were retrospectively analyzed, and an association analysis between genotype and phenotype was conducted. Result: We identified 15 novel and two recurrent ACAN gene variants in 16 different pedigrees that included index patients with short stature. Among the patients with ACAN variants, 12 of 18 had advanced bone age and 7 of 18 received growth hormone therapy, 5 (71.4%) of whom exhibited variable levels of height standard deviation score improvement. Further analysis showed that patients with ACAN truncating variants had shorter height standard deviation scores (p = 0.0001) and larger bone age–chronological age values (p = 0.0464). Moreover, patients in this Asian population had a smaller mean bone age–chronological age value than those that have been determined in European and American populations (p = 0.0033). Conclusion: Our data suggest that ACAN mutation is a common cause of short stature in China, especially among patients with a family history of short stature but also among those who were born short for their gestational age without a family history. Patients with truncating variants were shorter in height and had more obvious advanced bone age, and the proportion of patients with advanced bone age was lower in this Asian population than in Europe and America.

Evaluation of Growth Hormone Therapy in Seven Chinese Children With Familial Short Stature Caused by Novel ACAN Variants

ObjectiveACAN gene variants are an important cause of familial short stature (FSS). Appropriate growth-promoting therapies effectively improve the patient height. Here, we report a therapeutic assessment of cases of seven families of FSS patients with heterozygous ACAN variants. Our findings provide a valuable theoretical basis for the clinical diagnosis and treatment of this disease.MethodsFrom December 2020 to June 2021, 32 FSS patients were examined in Tianjin Medical University General Hospital (Tianjin, China) by whole-exome sequencing to determine whether ACAN variants were present. Their clinical data were summarized and scrupulously analyzed.ResultsWe found seven novel heterozygous ACAN variants: c.1051 + 2T > A, c.313T > C (p.S105P), c.2660C > G (p.S887X), c.2153C > A (p. T718K), c.7243delG (p.D2415Tfs*4), c.2911G > T (p.G971X), c.758-7T > C. All seven patients had proportionate short stature and mild skeletal dysplasia. Endocrine examination results were normal. Only one of the patients had an advanced bone age (1.1 years older than chronological age), whereas the other patients had normal bone ages. All of them had a family history of short stature, with or without osteoarthritis or intervertebral disc disease. All seven patients accepted treatment with recombinant human growth hormone (rhGH) and were regularly followed up. One patient did not come at the follow-up visit. The height of the remaining six patients before and after the treatment was −2.89 ± 0.68 SDS, −1.91 ± 0.93 SDS, respectively, with a treatment course of 1.85 ± 1.91 years. A good therapeutic response was observed in all of them.ConclusionsIn this study, seven novel heterozygous variants in ACAN were discovered, which expanded the spectrum of the already established ACAN pathogenic variants. In FSS cohort, the proportion of ACAN variants accounted was large. The treatment with rhGH effectively increased the patient height, but further studies with longer follow-up periods and more extensive observations are required to elucidate the long-term effect.

Prevalence of Short Stature Among Children Aged 5-12 Years Old in Taif City, Saudi Arabia

Background: Short stature is one of the most common and frequent diagnosis in children investigated by pediatricians in everyday practice. The aim of this study was to analyse the prevalence of short stature in children between 5 to 12 years of age in Taif City, Saudi Arabia. Methods: This is a cross-sectional study performed on children where height was measured for all participants and an average of three measurements was recorded. A questionnaire on various parameters influencing short stature such as height of parents, birth history, history of illness, family history of short stature and chronic illness were completed by the children’s guardian. Results: Out of 314 children, 188 children were male (59.87%) and 126 were female (40.13%). The overall prevalence rate of short stature was 33.68%. Regarding male participants, 29 were identified as short stature (15.43%) compared to 23 females that were identified as short stature (18.25%). One male and two females with short stature were born prematurely. The most common etiology for short stature was familial short stature with 40.8% followed by malnutrition which was 24.2%. Growth hormone deficiency was the most common endocrinological cause for short stature (9.7%) followed by hypothyroidism (7.6%). Chronic kidney disease was the most common non-endocrinological cause (3.4%). Meanwhile, other disorders were found such as celiac disease (0.5%) and Turner’s Syndrome (0.3%).

A High Proportion of Novel ACAN Mutations and Their Prevalence in a Large Cohort of Chinese Short Stature Children.

ContextAggrecan, encoded by the ACAN gene, is the main proteoglycan component in the extracellular cartilage matrix. Heterozygous mutations in ACAN have been reported to cause idiopathic short stature. However, the prevalence of ACAN pathogenic variants in Chinese short stature patients and clinical phenotypes remain to be evaluated.ObjectiveWe sought to determine the prevalence of ACAN pathogenic variants among Chinese short stature children and characterize the phenotypic spectrum and their responses to growth hormone therapies.Patients and MethodsOver 1000 unrelated short stature patients ascertained across China were genetically evaluated by next-generation sequencing–based test.ResultWe identified 10 novel likely pathogenic variants and 2 recurrent pathogenic variants in this cohort. None of ACAN mutation carriers exhibited significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect is estimated to be 1.2% in the whole cohort; it increased to 14.3% among those with advanced bone age and to 35.7% among those with both advanced bone age and family history of short stature. Nonetheless, 5 of 11 ACAN mutation carries had no advanced bone age. Two individuals received growth hormone therapy with variable levels of height SD score improvement.ConclusionOur data suggest that ACAN mutation is 1 of the common causes of Chinese pediatric short stature. Although it has a higher detection rate among short stature patients with advanced bone age and family history, part of affected probands presented with delayed bone age in Chinese short stature population. The growth hormone treatment was moderately effective for both individuals.

Dental and Craniofacial Characteristics in Patients With 14Q22.1-Q22.2 Deletion: A Case Series.

This case series is a follow-up report focusing on dental and facial characteristics in patients with a rare microdeletion in chromosome 14q22.1-q22.2. Usually, these patients have severe ocular, brain, and digital abnormalities. However, this case series shows that clinical presentation can be mild. Four relatives spanning 3 generations were diagnosed with a familial autosomal dominant 2.79 Mb microdeletion in chromosome 14q22.1-q22.2. Genetic screening was done by the Bacterial Artificial Chromosome array-comparative genome hybridization and was confirmed by the fluorescence in situ hybridization technique. Dental and craniofacial data were collected from medical files, clinical examinations, clinical photos, panoramic and cephalometric radiographs, and dental casts. Written informed consent for scientific use was obtained for all family members. No larger syndrome could be identified. All cases had similar facial red flag characteristics, consisting of a long face with retrognathia and open mouth relation, associated oral clefts in varying degrees, depressed nasal bridge, delayed tooth development, hypertelorism, and low-set angular ears. The dental casts showed a distal molar occlusion and a lack of space in the dental arches. Developmental delay was noted together with limb defects such as poly- and syndactyly. Microphthalmia and hearing loss were present in the most severe cases. This rare congenital disorder, associated with facial dysmorphia, oral clefts, and tooth agenesis, can remain undiagnosed until adulthood. A family history of short stature, developmental delay, poly- or syndactyly, and micropthalmia are suggestive features. Similar reports help to raise awareness among dental practitioners, leading to an early genetic diagnosis.

Acanthosis nigricans in a Chinese girl with FGFR3 K650\u2009T mutation: a case report and literature review

BackgroundAcanthosis nigricans (AN) is a clinical manifestation featured by velvety brown plaques in skin folds that occurs in some hereditary and syndromic disorders. Fibroblast growth factor receptor 3 (FGFR3) mutations have been identified as one of the genetic causes of inherited AN.Case presentationA 17-year-old Chinese female had presented generalized acanthosis nigricans since she was 4 years old. She yielded no family history of short stature or AN. Apart from a short stature, no skeletal defects, neurological defects or other abnormalities were found. To identify the aetiology of the clinically diagnosed AN, we screened the proband for genetic mutations using whole exome sequencing. A heterozygous mutation (c.1949A > C, p.Lys650Thr) in FGFR3 was found in the proband. To date, 26 cases of AN harbouring this specific gene mutation have been reported in the literature, and only one child carried a de novo mutation instead of inheriting the specific mutation from their parents. The present case is the first-reported Chinese patient with isolated AN with a de novo K650 T mutation in FGFR3.ConclusionsWe reported a new case of AN caused by a heterozygous mutation (c.1949A > C, p.K650 T) in FGFR3, and review the past reports of AN with the same gene mutation. Sequencing of the FGFR3 gene is a feasible approach to identify the aetiology of AN, especially for early onset extensive AN.

A family history of short stature

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Compound heterozygosity for two GHR missense mutations in a patient affected by Laron Syndrome: a case report

BackgroundMutations localized in the Growth Hormone Receptor (GHR) gene are often associated with the pathogenesis of Laron Syndrome, an autosomal recessive hereditary disorder characterized by severe growth retardation. Biochemically, patients present normal to high circulating GH levels, in presence of very low or undetectable IGF-I levels, which do not rise after rhGH treatment.Case presentationWe describe the case of a 3.8 years old girl with symmetrical short stature (−3.76 SDS), low IGF-1 and IGFBP-3, in presence of normal GH levels. Parents were not relatives and there was no family history of short stature. During the second day of birth, she developed severe hypoglycaemia that required glucose infusion. She presented frontal bossing and depressed nasal bridge. IGF-1 generation test showed no response, suggesting a GH resistance evidence. In the hypothesis of Laron Syndrome, we decided to perform a molecular analysis of Growth Hormone Receptor (GHR) gene. This analysis demonstrated that the patient was compound heterozygote for two missense mutations.ConclusionsGHR gene mutations are a well demonstrated cause of GH insensitivity. In heterozygous patients, probably the normal stature may be achieved by a compensatory mechanism of GH secretion or signalling. On the contrary, in homozygous or compound heterozygous patients these compensatory mechanisms are inadequate, and short stature may be the consequence.

Prevalence of stunted growth in children less than 5-year old in Qualyoubia governorate

Objectives The objective of this study was to study the prevalence of stunted growth in children under 5 years of age (in primary healthcare) in a rural area, in Qualyoubia governorate. Background Stunting remains an important problem in Egypt, where ∼ one-third of children under 5 years of age are affected. Patients and methods This is a cross-sectional study that was conducted on 1255 cases. All studied children were subjected to history taking, complete physical examination [height (cm), length (cm), weight (kg)], and laboratory investigations (measurement of hemoglobin level). Then, the stunting group was compared with the control group regarding their different characteristics according to national Egyptian growth chart. Results The prevalence of stunted growth in children under 5 years of age was 13.32%; stunted growth was significantly associated with age of children (stunting was more in children aged <24 months) (P = 0.005), socioeconomic level (P = 0.004), family history of short stature (P < 0.05), family size more than five (P = 0.004), and low hemoglobin level (P < 0.001). Conclusion The prevalence of stunted growth in children under 5 years of age attending primary healthcare in a rural area in Qualyoubia governorate was 13.32%.

Etiology of Short Stature in First Five Years of Life

Dear Editor, Short stature (SS) is one of the common causes of referrals to pediatric endocrinologists. The most common causes of SS included familial SS and constitutional growth delay, but a wide spectrum of the diseases can result to SS. It is evident that the correct understanding of the etiology of short stature in any society can be a good guide for diagnostic and therapeutic policies. So, many endocrine centers attempted to study the etiology of SS in their areas. This is a descriptive study and conducted in Kashan University of Medical Sciences. Any child under 5 years with a height less than the 3rd percentile of standard growth curves has been enrolled. Data including age, gender, family history of short stature, history of chronic diseases such as bowel disease, malnutrition, celiac disease and drug history from the parents or the child were obtained. The height and weight of the children and parents were measured. The physical examination was performed to find the cause of short stature. Preliminary tests were performed for all children including CBC, thyroid function tests, electrolytes, urinalysis and creatinine. Other tests based on the suspected disorders. A left wrist and hand X-ray was performed for all cases to determine bone age and evidences of bone dysplasia. A total of 67 children were included, the mean age was 2.5 ± 1.45 years (39 male and 28 female). Average height was 77.36 ± 14.6 cm and mean weight was 9.26 ± 3.4 kg. Overall the most common cause was short stature in a background of low birth weight (LBW) (23.9%) followed by constitutional growth delay (14.9%), familial short stature (11.9%) and growth hormone deficiency (10.5%). Most common causes of short stature in different age groups included: 0 2 years: Short stature in a background of low birth weight was the most common (n = 12, 44.4%) followed by the metabolic disorders and syndromes each of the 4 patients (14.8%). 2-5 years: Familial short stature (20.5 %), different syndromes (20.5 %) and constitutional short stature (17.9%). Metabolic disorders: Cystinosis, phenylketoneuria and organic academia. Syndromes: Down syndrome (most common), Noonan syndrome, Turner syndrome and unknown syndromes. Other causes: Nephrogenic diabetes insipidus, pycnodysostosis, chronic hepatitis, achondroplasia and hypochondroplasia. One case of hypochondroplasia also had hypothyroidism. One patient with achondroplasia had also growth hormone deficiency. Growth hormone deficiency is a quietly treatable cause of short stature in children and had a relatively high prevalence in our study (10.5%). Growth hormone deficiency has been reported in other studies with a prevalence of 34.3% in Majcher et al. study, 15% in Chowdhury et al. study and 30% in Mohammadian et al. study [1-3]. An interest finding in our study was the association of two important cause of short stature in some cases such as hypothyroidism in a girl with achondroplasia and growth hormone deficiency in another girl. The prevalence of chromosomal abnormalities in our work was relatively high (9%) and Down syndrome was the most common disorder. A prevalence of 20% of chromosomal abnormalities in short stature children also has been reported [2].

Autosomal dominant Kenny-Caffey syndrome with congenital hypoparathyroidism, short stature and normal intellect: a case report

Kenny-Caffey syndrome (KCS) is characterized by proportionate short stature, cortical thickening and medullary stenosis of tubular bones, delayed closure of anterior fontanelle, eye abnormalities, and hypoparathyroidism. The autosomal dominant form (KCS Type 2) caused by mutations in FAM111A is distinguished from the autosomal recessive form (KCS Type1), caused by mutations in TBCE gene, by the absence of mental retardation. Our proband presented on day 8 of life with hypocalcaemic seizures secondary to hypoparathyroidism. Normocalcaemia was achieved with IV calcium gluconate and maintained by oral calcium carbonate 100mg BD and calcitriol 0.1mcg BD for the first 2 years of life while serum PTH remained low at <0.3pmol/L. There has been no evidence of nephrocalcinosis on follow up. The dose of supplemental calcium and calcitriol is being gradually reduced. She also has persistent mild microcytic anaemia with normal iron stores. Her phenotype included small hands and feet, triangular hypoplastic and dystrophic nails, hypoplastic mid-face, macrocrania and large persistent fontanelles. Karotype and FISH for 22q11 deletion were normal. Initial investigations included a normal ECHO, renal ultrasound and MRI brain. Her neurodevelopment is normal but her growth is compromised. At 1 year, her length was 65.5cms (SDS -2.9) and at 3 years, her height was 80cms (SDS -3.8). There is no family history of short stature or hypoparathyroidism. She is growth hormone sufficient on pharmacological testing; however she has been commenced on growth hormone treatment based on her poor growth velocity and short stature. It is currently too early to determine response. A skeletal survey performed at 2 years of age was suggestive of KCS. Genetic testing revealed a heterozygous mutation c.1622C>A (p.Ser541Tyr) in FAM111A. However, the unusual nails, the reducing calcium requirement and the unexplained microcytic anaemia are unique to our patient. Written informed Consent for this patient has been taken including results of the genetic analyses and images according to the Institutional Ethics Committee procedures of our health service.

Phenotypic spectrum of m.3243A>G mitochondrial DNA mutation in children

BackgroundMitochondrial disease are multi-system disorders affecting virtually any organ and cause significant morbidity. The prevalence of mitochondrial DNA (mtDNA) disease is estimated at 1 in 5000, but epidemiological studies suggest...

Growth deceleration in a girl treated with imatinib

Imatinib is an inhibitor of tyrosine kinase as well as BCRABL, platelet-derived growth factor receptor (PDGF-R) and c-kit, and is becoming a first-line treatment for chronic myeloid leukemia (CML). In children, the long-term toxic effects related to the inhibition of tyrosine kinase are not yet well understood. A 6-year-old girl was diagnosed with BCR-ABL positive CML in the chronic phase in June 2003. After receiving imatinib (400 mg/m per day), molecular remission was achieved and persisted for 4 years without major side-effects. At the beginning of imatinib administration, the patient was aged 6 years, and her height was 114 cm (-0.7SD). Her growth rate decreased during these 4 years, and her height was 121 cm (-2.7SD) when she was aged 11 years. The patient followed the normal growth pattern since birth she had normal body proportions and appearance, no family history of short stature. Following extensive tests, she reached the normal GH peak after two stimulatory tests and other systemic diseases (endocrine disorder, renal failure, inflammatory disorders) were excluded. Additionally, we identified delayed bone age on X ray of her wrists at the age of 11 years (bone age was 7 years) and low bone mineral density was demonstrated on dual-energy X ray absorptiometry of the lumbar spine (0.576 g/m Z score less than -2.5SD for chronological age). Bone formation markers (serum osteocalcin, 8.5 ng/ml and bone specific alkaline phosphatase BAP, 30.0 U/L) were lower than those of age-matched healthy girls (reference range; osteocalcin 36–93 ng/ml, BAP 66–137 IU/l) and bone resorption marker (urinary deoxypyridinoline 5.8 nM/mMCre) was also lower (reference range 28–42 mM/mMCre), suggesting that effect of decreased bone formation exceeded that of decreased bone resorption. Because she had not been exposed to a long-term immunosuppressive steroid treatment and there were no other risk factor of inhibition of bone formation, we strongly suspected that imatinib treatment may have been associated with the low mineral density in this patient. After confirming the absence of detectable BCR-ABL trasnscript, imatinib was discontinued in October 2007, which subsequently resulted in gradual growth acceleration. However, because BCR-ABL transcript in her peripheral blood reappeared, she was prepared for allogeneic stem cell transplantation. We noted increased bone formation markers (BAP 110.9 U/L, osteocalcin 22.9 ng/ml) 8 months after discontinuation of imatinib, as well as an increased growth rate (6.2 cm over 8 months) (Fig. 1). The possibility that imatinib restrains bone resorption (by inhibiting c-Fms on osteoclasts) and stimulates bone formation (by inhibiting PDGF-R on osteoblats) has been reported in vitro [1–3], and adult CML patients actually have increased bone volume after long-term imatinib therapy [4]. Although bone metabolism in our patient differed from that in adults receiving imatinib, we suspect that growth deceleration and low bone mineral density in our patient were associated with imatinib administration. In September 2008 (11 months after discontinuation of imatinib), the patient has successfully achieved complete donor chimerism from an unrelated cord blood donor following reduced intensity conditioning with the expectation that she would achieve puberty and accelerated growth. T. Kimoto (&) M. Inoue K. Kawa Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan e-mail: tomiko@mch.pref.osaka.jp

High incidence of SHOX anomalies in individuals with short stature

Objective: To study the SHOX gene and the PAR1 region in individuals with short stature. Methods: The study involved 56 cases of dyschondrosteosis and 84 cases of idiopathic short stature...

Short Stature and Diagnostic Studies

Horner, Thorsson, and Hintz1 have recently reviewed their experience with constitutional short stature (CSS) as defined by short stature, a delayed bone age, no family history of short stature, and no pathologic etiology. Their coverage of this specific condition is excellent, but it raises several questions about short stature in general. First, whatever happened to the children with familial short stature (FSS)? FSS can be defined as a child with short stature, a normal bone age, and a family history positive for short stature.

Urinary cyclic adenosine 3′, 5′-monophosphate excretion in children of short stature: Effect of somatotropin

Excretion of urinary cyclic adenosine 3',5'-monophosphate (cAMP) was determined in twenty-four children of short stature and in sixteen normal children. Of the patients, eight suffered from anterior panhypopituitarism, six from isolated deficiency or somatotropin, seven had a family history of short stature, and three had growth failure of pre-natal onset. In children suffering from anterior panhypopituitarism or from isolated somatotropin deficiency, excretion of cAMP was found to be depressed. Short-term administration of purified somatotropin in normal therapeutic dose (3.4 mg per 1.7 m2 i.m. daily for 5 days) had no effect on urinary cAMP, but reduced urine volume in all patient groups. During somatotropin treatment there was a positive correlation between changes in urine volume and nitrogen balance (r = 0.67).

FAMILIAL GROWTH RETARDATION ASSOCIATED WITH GENETICALLY DETERMINED BRAIN DYSFUNCTION

Three brothers, ages 12, 7 and 6 years with a striking similar history of psychomotor retardation, developmental defects in speech and reading, low I.Q.'s behavioral disabilities and hyperactivity were found to be retarded in growth and skeletal maturation. There was a positive family history of short stature and mental retardation. The oldest sibling had panhypopituitarism as indicated by lack of increase in serum HGH during insulin, arginine and deep sleep, low FBI and T4, low 24 hr. urinary 17KGS and lack of response to metyrapone. Administration of 25U of ACTH produced an increase in plasma cortisol levels from 3.2 meg/100 ml to 19.4. The other two had normal increases in serum HGH and normal thyroid and adrenal functions. A normal increase in serum TSH after administration of 7 μg/kg of TRF in the three indicated an intact pituitary gland. The increase in nitrogen balance, plasma FFA, insulin release, and the marked calciuria and hydroxyprolinuria produced by administration of HGH ruled out peripheral unresponsiveness to HGH. It is possible that a genetically determined brain lesion affected the hypothalamic centers controlling the anterior pituitary gland, resulting in a multiple deficiency of releasing factors in the oldest and a decreased secretion of an unknown hypothalamic factor involved in promoting growth in the other two. (Supported by NIH Grant RR-318)

Short Stature and Growth Hormone Deficiency Due to Histiocytosis X

Diabetes insipidus (DI) is a common complication of histiocytosis X. Anterior pituitary function has not been previously systematically studied. Both anterior and posterior pituitary function has been evaluated in 11 children with histiocytosis. The following methods were used. Insulin hypoglycemia and arginine infusion for HGH, serum PBI, T4, and 191I uptake for thyroid function, and metyrapone stimulation for adrenal function. Concentrating ability was used as an index of vasopressin release. Gonadotropin was assessed by physical examination only. In 6 patients, only vasopressin and growth hormone (GH) response was studied. In 5 thyroid and adrenocortical evaluation was alos obtianed. Of the 11 children, 4 were of normal height for age, while 7 were below the 3rd percentile. Those children with normal height all had normal GH response. Two of them had DI with normal thyroid and adrenal function. Of the 7 children with retardation of linear growth, 6 were found to be GH deficient. The 1 child with normal GH had a strong family history of short stature. Five had DI and all were GH deficient. Thyroid studies were normal in 2 and adrenal studies in 3 of these. One child had histiocytosis of the thyroid gland with goiter and hypothyroidism. In 3 children of adolescent age with short stature, GH deficiency and DI, puberty was delayed. This study documents that histocytosis may involve the anterior and/or posterior pituitary. An adequate clinical evaluation should include study of the anterior pituitary.