Results are discussed in terms of communication potential and the need to address AAC in trisomy 18 and 13.

CASE: John is a 4-year-old boy with autism spectrum disorder (ASD) and developmental delay who presented with concerns about increasing aggressive behavior at a follow-up visit with his developmental-behavioral pediatrician. Diagnosis of ASD was made via Diagnostic and Statistical Manual of Mental Disorders, 5th version criteria at initial evaluation at 34 months. Medical history at that time was pertinent for rapid linear growth since the age of 1 and recent pubic hair growth and penile enlargement. Family history was significant for early puberty in a maternal uncle and 4 distant maternal relatives. Standardized testing included administration of the Childhood Autism Rating Scale 2-Standard, which was consistent with severe symptoms of ASD, and the Mullen Scales of Early Learning, which indicated moderate delay in fine motor skills and expressive language and severe delay in receptive language and visual receptive skills. At initial assessment, John's parents also reported a pattern of aggressive behavior, which included frequent hitting of other children at childcare, consistently forceful play with peers and family members, and nightly tantrums with hitting and throwing at bedtime. Triggers of aggressive behavior included other children taking his toys, transition away from preferred activities, and being told “no.” John was concurrently evaluated by a pediatric endocrinologist at 34 months. At that assessment, his height Z-score was +2.5, and he had Tanner 2 pubic hair, Tanner 3 genitalia, and 6 cc testicular volumes. Radiograph of the hand revealed a bone age of 6 years (+7.8 S.D.). Laboratory studies revealed a markedly elevated testosterone level and low gonadotropin (luteinizing hormone [LH] and follicle-stimulating hormone) levels and a normal dehydroepiandrosterone sulfate, suggestive of peripheral precocious puberty. Targeted genetic testing with sequencing of the LHCGR gene revealed a heterozygous D578G mutation resulting in the rare condition Familial Male-Limited Precocious Puberty (FMPP), characterized by constitutive activation of the LH receptor.1 FMPP, also referred to as testotoxicosis, was attributed as the cause of John's peripheral precocious puberty. By the age of 4, John's height Z-score was +3.1, his genitalia larger, and his bone age 10 years (+10.3 S.D.). His parents elected to start off-label therapy with bicalutamide (a nonsteroidal antiandrogen) and anastrazole (an aromatase inhibitor), recommended by the endocrinologist. Unexpectedly, as John's hyperandrogenism was treated, John's family reported intensified aggression toward other children and adults, especially at school, in addition to multiple daily instances of biting when upset. What is your next step in John's treatment of his challenging behavior? REFERENCE 1. Shenker A, Laue L, Kosugi S, et al. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature. 1993;365:652–654.

Pectus carinatum and excavatum have multiple genetic associations. We report on a novel association of these deformities in a 34-month-old male and his father, likely due to a small intragenic deletion of MNAT1 (ménage a trois 1 gene). Both individuals share a deletion of MNAT1 located at 14q23.1 and an interstitial duplication of CHRNA7 located at 15q13.3. Deletion of MNAT1 has been associated with connective tissue abnormalities and is likely the etiology of the malformations, whereas the duplication of CHNRA7 is unlikely related due to the lack of association with any such connective tissue abnormalities.

A de novo 1.2 Mb-4q25 proximal microdeletion encompassing the genes COL25A1 and ELOVL6 has been reported once in a 20-year-old woman. She had dysmorphic features and a complex behavioral phenotype, as described in table 1 [Verhoeven et al., 2013]. Through genotype-phenotype correlation, COL25A1 and EGF were proposed as candidate genes responsible for her unique phenotype [Verhoeven et al., 2013]. Prior to that publication, 4q25 microdeletion syndrome was mostly associated with Axenfeld-Rieger syndrome, with 95% of the affected patients having mutations or deletions involving the PITX2 gene or related upstream regulatory genes, often in a haploinsufficient manner [Amendt et al., 2000;Becker et al., 2003]. Here, we report on 2 additional patients (a child and his mother) having a smaller, but overlapping deletion characterized by a common behavioral and physical phenotype. The 3 patients combined suggest the existence of a novel 4q25 proximal deletion syndrome. Patients and Methods Clinical Case FindingsA 29-month-old Caucasian boy presented to our clinic with his 19-year-old mother. His medical history included birth via Cesarean section for fetal distress, eczema, and seasonal allergies. Key Words COL25A1 · Developmental delay · EGF · Hypotelorism · Hypotonia · Mandible asymmetry · Microdeletion 4q25Abstract Haploinsufficient microdeletions within chromosome 4q25 are often associated with Axenfeld-Rieger syndrome. A de novo 4q25 deletion, 675 kb proximal to PITX2 , has previously been reported once in an adult patient. The patient did not have Axenfeld-Rieger anomaly, but instead had intellectual disability and a complex behavioral phenotype with withdrawn, stereotypic, and ritualistic behavior. Array comparative genome hybridization demonstrated a smaller, overlapping 4q25 deletion in a 2-year-old patient and his mother, both having significant phenotypic overlap with the initially reported patient. All 3 patients have distinct facial features (including mild hypotelorism and subtle mandibular asymmetry), developmental delay, and complex behavioral difficulties. A genotype-phenotype correlation narrows the shared phenotype to a common COL25A1 gene aberration and proposes that the concurrent EGF gene loss has a significant impact on the phenotypic severity. Overall, our patients provide data to support the existence of a novel 4q25 proximal deletion syndrome.

To better understand adolescents experiencing peer victimization, ostracism, and emotional health problems, this study aimed to describe a cohort of middle school students identified as having school peer-related social difficulties as 2 groups: those with mental health diagnoses (MHDs; n = 17) and those without diagnoses (n = 8). Participants were administered a test battery to examine communication ability, social responsiveness, social activity, ostracism, victimization, and emotional health. Results showed that adolescents with MHDs, relative to those without, scored significantly lower on measures of communication ability, social responsiveness, and social activity but similarly on measures of victimization, ostracism, and internalizing/externalizing factors. Results suggest that adolescents with and without MHDs can endure ostracism and peer victimization to a similar extent. Because ostracism and victimization have serious morbidity in adolescents, physicians and caregivers must look for signs in all adolescents, irrespective of MHD. Recommendations for appropriate primary care management are discussed.