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Advanced Neurology Genetics of neurodevelopmental disorders in Mexico

Table 1. (Continued)
No. Gender Age of Epilepsy ASD ADHD CD MD ID Dysmorphism Dysfunction Definitive diagnosis Familial
onset (Gene) study
22 β F 1 year X X Facial and limb Intellectual disability No genetic diagnosis -
dysmorphism (TANGO carrier,
VUS)
23 β M At birth X X X X Macrosomia Intellectual disability No genetic diagnosis -
(pseudogene GALC
carrier)
24 β M At birth X X Coloboma, Arrhythmia CHARGE syndrome -
microtia, (no mutation
thumb anomaly, detected) FANCF
congenital heart (pseudogene carrier)
disease
T 15 M9 F - 11 11 6 18 11 6 - - 11 families
30 members
Notes: Cases that had a definitive diagnosis with the study; cases with variants of uncertain significance (VUS) related to the clinical presentation;
δ
θ
β cases in which the study ruled out the Mendelian diseases most frequently associated with their clinical presentations.
Abbreviations: ASD: Autism spectrum disorder; ADHD: Attention deficit hyperactivity disorder; CD: Communication disorder; ID: Intellectual
disability; MD: Motor disorder; UPD: Uniparental disomy.
Eleven patients with NDDs and epilepsy were and there is a cousin with similar signs. The homozygous
studied, and a genetic diagnosis was confirmed in nine mutation of CFRL1 c.151_153del (p.Leu51del) is described
of them (81.8%). Among the five patients diagnosed as a benign polymorphism combined with a likely benign
with ASD and epilepsy, four exhibited mutations in mutation in HCN1 c.192_206dup (p.Gly70_Gly74dup),
SYNGAP1, CDKL5, MECP2, and CRLF1. A heritable, which is heterozygous and inherited from the father.
yet likely benign mutation in HCN1 was also identified, Patient 7, who exhibited motor delay, visual and
manifesting as febrile crises in both the father and the auditory impairments, epilepsy, and lacked verbal
patient. In addition, a VUS was detected in SNCA8. language capabilities, was born from a consanguineous
Mutations in PTEN, PURA, PNPT1, NF1, and six marriage that previously resulted in a stillbirth diagnosed
VUSs were identified across conditions including ASD, with a genetic condition due to a homozygous mutation
communication disorders, and ADHD. NDDs and motor in DUOX2, that is, c.2182 G>A (p.Ala728Thr). The second
disabilities were associated with mutations in PNPT1, daughter carries a homozygous pathogenic mutation in
DMD, LAMP2, and COLQ. These findings are detailed PNPT1, that is, c.407G>A (p.Arg136His), associated with
in Table 2, which correlates specific genes with diagnoses autosomal recessive combined oxidative phosphorylation
and parental origins, following the study of the patient’s deficiency 13 (COXPD13). Patient 14 was diagnosed
relatives. In six patients, we identified genetic syndromes with PURA syndrome, characterized by the absence of
with very low prevalence caused by novel mutations, verbal language, long palpebral fissures, curly eyelashes,
including conditions related to SYNGAP1 synaptopathy, and drop-shaped fingertips. Patient 15 presented at birth
PURA syndrome, and mutations in CDKL5, MECP2, with a clinical picture suggestive of congenital amyoplasia,
and PTEN. In addition, two heritable conditions caused by a pathogenic exonic mutation in COLQ,
were diagnosed in consanguineous parents: Crisponi which leads to myasthenic syndrome (MIM 603034).
syndrome/cold-induced sweating syndrome and an The etiopathogenesis of this syndrome is intriguing, as
oxidative phosphorylation defect. These atypical cases are it is thought to be related to a vascular disruptive event
noteworthy and merit reporting. in the first trimester of gestation, under the influence of
Patient 4, with Crisponi syndrome or cold-induced susceptibility genes.
sweating, presented the classical neonatal-onset clinical In several patients, we detected pathogenic heterozygous
picture with crying, camptodactyly, disorders for mutations associated with recessive diseases, as detailed in
sucking, swallowing, feeding, the episodes of sweating Table 3. This information is particularly valuable for suspecting
induced by cold and body temperature dysregulation, congenital pathologies in contexts of consanguinity and
and hyperthermia of unspecified cause described in the endogamy prevalent in the region. The diseases identified
syndrome. The parents of this patient are consanguineous, in a carrier state include biotinidase deficiency (BTD),
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Volume 3 Issue 2 (2024) 5 doi: 10.36922/an.3359